|
1
|
Huang TY, Yang JJ. Non-targeted metabolomic profile of Leuconostoc mesenteroides-fermented milk reveals differentially expressed metabolites associated with electro-fermentation. Microb Cell Fact 2025; 24:46. [PMID: 39987182 PMCID: PMC11847352 DOI: 10.1186/s12934-025-02673-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 02/07/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Leuconostoc mesenteroides (L. mesenteroides) has known as an electrogenic probiotic bacterium. However, metabolites related to electro-fermentation in ferments of L. mesenteroides are not unveiled. RESULT Electrogenic L. mesenteroides fermentatively metabolized bovine milk to dense ferments with homogeneous particle-size distribution. A non-targeted metabolomics approach was performed on non-fermented and L. mesenteroides-fermented milk. A total of 917 metabolites were identified and quantified by ultra-high performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS-MS). Thirteen prokaryotic metabolic pathways associated with differentially expressed metabolites (DEMs) were revealed through Koto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Anthranilic acid (AA) and 3-hydroxyanthranilin acid (3-HAA), potentially as electron donors, and quinolinic acid, an electron donor precursor, in the tryptophan kynurenine pathway were significantly increased in the fermented milk. Histidine, arginine, and riboflavin involved in bacterial survival or bioelectricity production were elevated after fermentation. CONCLUSIONS Results indicate that electrogenic L. mesenteroides can mediate electro-fermentation to transform milk to a new nutritional source which is rich in electron donors reportedly acting as antioxidants.
Collapse
Affiliation(s)
- Tristan Yusho Huang
- Arizona College of Osteopathic Medicine, Midwestern University, Arizona, 85308, USA.
| | - John Jackson Yang
- Department of Medical Biochemistry, Universitas Kristen Indonesia, Jakarta, 13630, Indonesia
| |
Collapse
|
|
2
|
Ahmad M, Aduru SV, Smith RP, Zhao Z, Lopatkin AJ. The role of bacterial metabolism in antimicrobial resistance. Nat Rev Microbiol 2025:10.1038/s41579-025-01155-0. [PMID: 39979446 DOI: 10.1038/s41579-025-01155-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2025] [Indexed: 02/22/2025]
Abstract
The relationship between bacterial metabolism and antibiotic treatment is complex. On the one hand, antibiotics leverage cell metabolism to function. On the other hand, increasing research has highlighted that the metabolic state of the cell also impacts all aspects of antibiotic biology, from drug efficacy to the evolution of antimicrobial resistance (AMR). Given that AMR is a growing threat to the current global antibiotic arsenal and ability to treat infectious diseases, understanding these relationships is key to improving both public and human health. However, quantifying the contribution of metabolism to antibiotic activity and subsequent bacterial evolution has often proven challenging. In this Review, we discuss the complex and often bidirectional relationships between metabolism and the various facets of antibiotic treatment and response. We first summarize how antibiotics leverage metabolism for their function. We then focus on the converse of this relationship by specifically delineating the unique contribution of metabolism to three distinct but related arms of antibiotic biology: antibiotic efficacy, AMR evolution and AMR mechanisms. Finally, we note the relevance of metabolism in clinical contexts and explore the future of metabolic-based strategies for personalized antimicrobial therapies. A deeper understanding of these connections is crucial for the broader scientific community to address the growing crisis of AMR and develop future effective therapeutics.
Collapse
Affiliation(s)
- Mehrose Ahmad
- Weill Cornell Medical College, Cornell University, New York, NY, USA
| | - Sai Varun Aduru
- Department of Chemical Engineering, University of Rochester, Rochester, NY, USA
| | - Robert P Smith
- Cell Therapy Institute, Kiran Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
- Department of Medical Education, Kiran Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Zirui Zhao
- Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA
| | - Allison J Lopatkin
- Department of Chemical Engineering, University of Rochester, Rochester, NY, USA.
- Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
- Department of Biomedical Engineering, University of Rochester Medical Center, Rochester, NY, USA.
| |
Collapse
|
|
3
|
Fan Z, Khan MM, Wang K, Li Y, Jin F, Peng J, Chen X, Kong W, Lv X, Chen X, Qiu B, Wang X. Disruption of midgut homeostasis by microplastics in Spodoptera frugiperda: Insights into inflammatory and oxidative mechanisms. JOURNAL OF HAZARDOUS MATERIALS 2025; 487:137262. [PMID: 39842122 DOI: 10.1016/j.jhazmat.2025.137262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 01/05/2025] [Accepted: 01/16/2025] [Indexed: 01/24/2025]
Abstract
Microplastics have evolved as widespread contaminants in terrestrial and aquatic environments, raising significant environmental concerns due to their persistence and bioaccumulation. In this study, we investigated the toxicity of polyethylene microplastics (PE-MPs) on the agricultural insect, Spodoptera frugiperda. Maize leaves containing three sizes (0.5 μm, 5 μm, and 50 μm) of PE-MPs were fed to fall armyworm larvae for 12 days at concentrations of 1.25 g/ L, 5 g/L, and 20 g/L. The results showed that smaller size and higher concentration of microplastics led to increased toxicity. Furthermore, different sizes and maximum concentrations of PE-MPs were selected for subsequent experiments to observe changes in histological and enzymatic biomarkers, midgut microbiome, and metabolic responses. Following PE-MPs exposure, inflammation signs and oxidative stress were detected in the midgut. Significant changes were also observed in midgut microbiota and metabolomes, most related with oxidative stress, inflammatory disorders, and energy metabolism. These results provide evidence of midgut damage and alterations in the microbiota and metabolome of S. frugiperda because of PE-MPs exposure, highlighting the harm that microplastics can inflict on agricultural insects. Additionally, the study lays a theoretical foundation for future research on the transmission of microplastics through the food chain in agricultural ecosystems.
Collapse
Affiliation(s)
- Zeyun Fan
- Engineering Research Center of Biocontrol, Ministry of Education Guangdong Province, South China Agricultural University, Guangzhou 510640, China; Guangdong Provincial Key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Shaoguan University, Shaoguan 512005, China
| | - Muhammad Musa Khan
- Hainan Institute of Zhejiang University, Yazhou Bay Science and Technology City, Sanya 572000, China
| | - Kai Wang
- Department of Computational Medicine and Bioinformatics, School of Medicine, University of Michigan, Ann Arbor, MI 48109, United States
| | - Yihan Li
- Engineering Research Center of Biocontrol, Ministry of Education Guangdong Province, South China Agricultural University, Guangzhou 510640, China
| | - Fengliang Jin
- Engineering Research Center of Biocontrol, Ministry of Education Guangdong Province, South China Agricultural University, Guangzhou 510640, China
| | - Jing Peng
- Engineering Research Center of Biocontrol, Ministry of Education Guangdong Province, South China Agricultural University, Guangzhou 510640, China
| | - Xinyi Chen
- Engineering Research Center of Biocontrol, Ministry of Education Guangdong Province, South China Agricultural University, Guangzhou 510640, China
| | - Weizhen Kong
- Engineering Research Center of Biocontrol, Ministry of Education Guangdong Province, South China Agricultural University, Guangzhou 510640, China
| | - Xiaolu Lv
- Engineering Research Center of Biocontrol, Ministry of Education Guangdong Province, South China Agricultural University, Guangzhou 510640, China
| | - Xiaoyuan Chen
- Guangdong Provincial Key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Shaoguan University, Shaoguan 512005, China
| | - Baoli Qiu
- Engineering Research Center of Biotechnology for Active Substances, Ministry of Education, Chongqing Normal University, Chongqing 401331, China.
| | - Xingmin Wang
- Engineering Research Center of Biocontrol, Ministry of Education Guangdong Province, South China Agricultural University, Guangzhou 510640, China.
| |
Collapse
|
|
4
|
Liu HY, Li S, Ogamune KJ, Ahmed AA, Kim IH, Zhang Y, Cai D. Fungi in the Gut Microbiota: Interactions, Homeostasis, and Host Physiology. Microorganisms 2025; 13:70. [PMID: 39858841 PMCID: PMC11767893 DOI: 10.3390/microorganisms13010070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 12/25/2024] [Accepted: 12/30/2024] [Indexed: 01/27/2025] Open
Abstract
The mammalian gastrointestinal tract is a stage for dynamic inter-kingdom interactions among bacteria, fungi, viruses, and protozoa, which collectively shape the gut micro-ecology and influence host physiology. Despite being a modest fraction, the fungal community, also referred to as mycobiota, represents a critical component of the gut microbiota. Emerging evidence suggests that fungi act as early colonizers of the intestine, exerting a lasting influence on gut development. Meanwhile, the composition of the mycobiota is influenced by multiple factors, with diet, nutrition, drug use (e.g., antimicrobials), and physical condition standing as primary drivers. During its establishment, the mycobiota forms both antagonistic and synergistic relationships with bacterial communities within the host. For instance, intestinal fungi can inhibit bacterial colonization by producing alcohol, while certain bacterial pathogens exploit fungal iron carriers to enhance their growth. However, the regulatory mechanisms governing these complex interactions remain poorly understood. In this review, we first introduce the methodologies for studying the microbiota, then address the significance of the mycobiota in the mammalian intestine, especially during weaning when all 'primary drivers' change, and, finally, discuss interactions between fungi and bacteria under various influencing factors. Our review aims to shed light on the complex inter-kingdom dynamics between fungi and bacteria in gut homeostasis and provide insights into how they can be better understood and managed to improve host health and disease outcomes.
Collapse
Affiliation(s)
- Hao-Yu Liu
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (H.-Y.L.); (S.L.); (K.J.O.)
- Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, Yangzhou University, Yangzhou 225009, China
- Joint International Research Laboratory of Agricultural & Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
| | - Shicheng Li
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (H.-Y.L.); (S.L.); (K.J.O.)
- Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, Yangzhou University, Yangzhou 225009, China
- Joint International Research Laboratory of Agricultural & Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
| | - Kennedy Jerry Ogamune
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (H.-Y.L.); (S.L.); (K.J.O.)
- Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, Yangzhou University, Yangzhou 225009, China
- Joint International Research Laboratory of Agricultural & Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
| | - Abdelkareem A. Ahmed
- Department of Veterinary Science, Botswana University of Agriculture and Natural Resources, Private Bag 0027, Gaborone P.O. Box 100, Botswana;
| | - In Ho Kim
- Department of Animal Resource & Science, Dankook University, 119 Dandero, Donnamgu Cheonan, Cheonan-si 31116, Republic of Korea;
| | - Yunzeng Zhang
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China;
| | - Demin Cai
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; (H.-Y.L.); (S.L.); (K.J.O.)
- Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, Yangzhou University, Yangzhou 225009, China
- Joint International Research Laboratory of Agricultural & Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
| |
Collapse
|
|
5
|
Rong W, Wei Y, Chen Y, Huang L, Huang S, Lv Y, Guan D, Li X. 16S rRNA Sequencing Analysis Uncovers Dose-Dependent Cupric Chloride Effects on Silkworm Gut Microbiome Composition and Diversity. Animals (Basel) 2024; 14:3634. [PMID: 39765538 PMCID: PMC11672621 DOI: 10.3390/ani14243634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 12/11/2024] [Accepted: 12/14/2024] [Indexed: 01/11/2025] Open
Abstract
Copper-based pesticides are extensively used in agriculture, yet their impacts on beneficial insects remain poorly understood. Here, we investigate how cupric chloride exposure affects the gut microbiome of Bombyx mori, a model organism crucial for silk production. Using 16S rRNA sequencing, we analyzed the gut bacterial communities of fifth-instar silkworm larvae exposed to different concentrations of cupric chloride (0, 4, and 8 g/kg) in an artificial diet. The high-dose exposure dramatically altered the microbial diversity and community structure, where the Bacteroidota abundance decreased from 50.43% to 23.50%, while Firmicutes increased from 0.93% to 18.92%. A network analysis revealed complex interactions between the bacterial genera, with Proteobacteria and Firmicutes emerging as key players in the community response to copper stress. The functional prediction indicated significant shifts in metabolic pathways and genetic information processing in the high-dose group. Notably, the low-dose treatment induced minimal changes in both the taxonomic composition and predicted functions, suggesting a threshold effect in the microbiome response to copper exposure. Our findings provide novel insights into how agricultural chemicals influence insect gut microbiota and highlight potential implications for silkworm health and silk production. This work contributes to understanding the ecological impacts of copper-based pesticides and may inform evidence-based policies for their use in sericulture regions.
Collapse
Affiliation(s)
- Wantao Rong
- Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology, Hechi University, Hechi 546399, China; (W.R.); (Y.W.); (Y.C.); (L.H.); (S.H.); (Y.L.)
- Guangxi Collaborative Innovation Center of Modern Sericulture and Silk, Hechi University, Hechi 546399, China
| | - Yanqi Wei
- Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology, Hechi University, Hechi 546399, China; (W.R.); (Y.W.); (Y.C.); (L.H.); (S.H.); (Y.L.)
- Guangxi Collaborative Innovation Center of Modern Sericulture and Silk, Hechi University, Hechi 546399, China
| | - Yazhen Chen
- Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology, Hechi University, Hechi 546399, China; (W.R.); (Y.W.); (Y.C.); (L.H.); (S.H.); (Y.L.)
- Guangxi Collaborative Innovation Center of Modern Sericulture and Silk, Hechi University, Hechi 546399, China
| | - Lida Huang
- Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology, Hechi University, Hechi 546399, China; (W.R.); (Y.W.); (Y.C.); (L.H.); (S.H.); (Y.L.)
| | - Shuiwang Huang
- Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology, Hechi University, Hechi 546399, China; (W.R.); (Y.W.); (Y.C.); (L.H.); (S.H.); (Y.L.)
| | - Yiwei Lv
- Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology, Hechi University, Hechi 546399, China; (W.R.); (Y.W.); (Y.C.); (L.H.); (S.H.); (Y.L.)
| | - Delong Guan
- Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology, Hechi University, Hechi 546399, China; (W.R.); (Y.W.); (Y.C.); (L.H.); (S.H.); (Y.L.)
- Guangxi Collaborative Innovation Center of Modern Sericulture and Silk, Hechi University, Hechi 546399, China
| | - Xiaodong Li
- Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology, Hechi University, Hechi 546399, China; (W.R.); (Y.W.); (Y.C.); (L.H.); (S.H.); (Y.L.)
- Guangxi Collaborative Innovation Center of Modern Sericulture and Silk, Hechi University, Hechi 546399, China
| |
Collapse
|
|
6
|
Sun S, Kong L, Hu F, Wang S, Geng M, Cao H, Tao X, Tao F, Liu K. Metabolic Alterations of Short-Chain Organic Acids in the Elderly Link Antibiotic Exposure with the Risk for Depression. Metabolites 2024; 14:689. [PMID: 39728470 DOI: 10.3390/metabo14120689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 12/04/2024] [Accepted: 12/05/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND Our previous study showed that antibiotic exposure was linked to depressive symptomatology in community-dwelling older adults in China. Our current study aims to explore the underlying mechanisms by assessing the intermediated effects of circulating short-chain organic acids (SCOAs) on this association. METHODS Depressive symptoms were screened by the 30-item Geriatric Depression Scale (GDS-30). Urinary concentrations of antibiotics and serum SCOAs were measured using a liquid chromatography-mass spectrometry method. RESULTS Increased exposure to sulfadiazine, azithromycin, tetracyclines, or veterinary antibiotics (VAs) was positively associated with GDS-30 scores. Tetracycline reduced levels of caproic acid, iso-butyric acid, and iso-caproic acid (iso-CA), with iso-CA concentration inversely correlating with GDS-30 scores, while β-hydroxybutyric acids showed a positive correlation. The mediating effect of serum iso-CA on the association between depression and ofloxacin, with a mediating effect of 25.3%, and the association between depression and tetracycline, with a mediating effect of 46.3%, were both statistically significant, indicating partial mediation. CONCLUSIONS Antibiotics may affect the levels of SCOAs in older adults and could potentially contribute to depressive symptoms by influencing alterations in serum iso-CA levels.
Collapse
Affiliation(s)
- Shujing Sun
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
| | - Li Kong
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
| | - Fangting Hu
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
| | - Sheng Wang
- Center for Scientific Research, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
| | - Menglong Geng
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Key Laboratory of Population Health Across Life Cycle, Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei 230032, China
- Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, No. 81 Meishan Road, Hefei 230032, China
| | - Hongjuan Cao
- Lu'an Center of Disease Control and Prevention, Lu'an 237000, China
| | - Xingyong Tao
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
| | - Fangbiao Tao
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Key Laboratory of Population Health Across Life Cycle, Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei 230032, China
- Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, No. 81 Meishan Road, Hefei 230032, China
| | - Kaiyong Liu
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Center for Big Data and Population Health of IHM, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China
- Key Laboratory of Population Health Across Life Cycle, Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei 230032, China
- Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, No. 81 Meishan Road, Hefei 230032, China
| |
Collapse
|
|
7
|
Zhang LL, Wu ZC, Li JY, Li HK, Liu ZM, Wang J, Tan BE. Ningxiang pig-derived Enterococcus hirae HNAU0516 ameliorates postweaning diarrhoea by promoting intestinal health and modulating the gut microbiota in piglets. Animal 2024; 18:101220. [PMID: 39213909 DOI: 10.1016/j.animal.2024.101220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 06/03/2024] [Accepted: 06/10/2024] [Indexed: 09/04/2024] Open
Abstract
Early weaning-induced stress precipitates diarrhoea, significantly curtailing the growth performance of piglets. A pivotal contributor to this postweaning affliction is the emergence of gut bacterial dysbiosis. Enterococcus hirae, a promising probiotic, has indicated unclear effects and mechanisms on intestinal health. In this study, we investigated the effects and underlying mechanisms of oral supplementation with Ningxiang pig-derived Enterococcus hirae HNAU0516 orally supplementation on the gut bacterial community, immune response and gut barrier function in piglets. 21 d age Duroc × (Landrace × Yorkshire) piglets with a similar BW were randomly allocated to two groups. The Enterococcus hirae HNAU0516 administration group was inoculated orally with Ningxiang pig-derived Enterococcus hirae HNAU0516 throughout the trial period. Conversely, the control group received the same volume of physiological saline. Our findings revealed that Enterococcus hirae HNAU0516 supplementation effectively reduced diarrhoea rates of piglets (P = 0.010). Notably, this probiotic promoted intestinal development and enhanced intestinal barrier function. It also showed potential anti-inflammatory properties. Furthermore, Enterococcus hirae HNAU0516 supplementation significantly remodelled the colonic microbiota and increased the production of acetate (P = 0.007). In conclusion, our study highlights that Ningxiang pig-derived Enterococcus hirae HNAU0516 improves postweaning diarrhoea by promoting intestinal development, enhancing intestinal barrier function, decreasing intestinal permeability, modulating intestinal microbiota, and increasing short-chain fatty acids production.
Collapse
Affiliation(s)
- L L Zhang
- College of Animal Science and Technology, Hunan Agricultural University, Key Laboratory for Quality Regulation of Livestock and Poultry Products of Hunan Province, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China
| | - Z C Wu
- College of Animal Science and Technology, Hunan Agricultural University, Key Laboratory for Quality Regulation of Livestock and Poultry Products of Hunan Province, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China
| | - J Y Li
- College of Animal Science and Technology, Hunan Agricultural University, Key Laboratory for Quality Regulation of Livestock and Poultry Products of Hunan Province, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China
| | - H K Li
- College of Animal Science and Technology, Hunan Agricultural University, Key Laboratory for Quality Regulation of Livestock and Poultry Products of Hunan Province, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China
| | - Z M Liu
- Hunan Nuoze Biological Technology Co., Ltd., Yiyang 413001, China
| | - J Wang
- College of Animal Science and Technology, Hunan Agricultural University, Key Laboratory for Quality Regulation of Livestock and Poultry Products of Hunan Province, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China
| | - B E Tan
- College of Animal Science and Technology, Hunan Agricultural University, Key Laboratory for Quality Regulation of Livestock and Poultry Products of Hunan Province, Changsha 410128, China; Yuelushan Laboratory, Changsha 410128, China.
| |
Collapse
|
|
8
|
Han S, Xu G, Zhang K, Ahmad S, Wang L, Chen F, Liu J, Gu X, Li J, Zhang J. Fermented Astragalus Powder, a New Potential Feed Additive for Broilers to Improve the Growth Performance and Health. Animals (Basel) 2024; 14:1628. [PMID: 38891675 PMCID: PMC11171317 DOI: 10.3390/ani14111628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 05/23/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
A total of 320 1-day-old broilers were randomly divided into five groups. The control group (CON) received a basal diet, while the FAP4, FAP2, and FAP1 groups were provided with the basal diet supplemented with 4%, 2%, and 1% fermented Astragalus powder, respectively. The unfermented Astragalus powder (UAP2) group was fed the basal diet supplemented with 2% UAP. Each group contained eight replicates of eight chicks each. The results revealed that the final BW and ADG in the FAP 1 and FAP2 were higher than those in the UAP2 and CON groups, while reducing F/G from day 14 to day 42. On day 42, the thymus index in the UAP and FAP groups as well as the bursa index in the FAP4 group showed significant increases compared to those in the CON group. Supplementation with 2% FAP elevated serum IgA levels in broilers on day 28 and day 42, and it also increased serum IgG levels on day 42. Furthermore, supplementation with 2% FAP elevated serum albumin (ALB) levels in broilers, while supplementation with 4% FAP increased serum (glucose) GLU levels in broilers on day 28. The serum biochemical parameters and pathological observation of the liver and kidney in the groups did not show any adverse effects on broilers' health. In addition, the serum total antioxidant capacity (T-AOC) level significantly increased in the FAP4 and FAP2 groups on day 28, and the malondialdehyde (MDA) level in both serum and liver tissue decreased in the FAP2 group on day 28 and day 42. Compared to the CON group, 2% FAP and 2% UAP supplementation reduced the relative abundance of Bacteroides and supplementation with 2% FAP increased the relative abundance of Alistipes on day 42. In conclusion, the dietary supplementation of FAP can enhance the growth performance, immune function, and antioxidant capacity and regulate microflora in broilers, of which 2% FAP is more effective. It indicates FAP exhibits significant application potential as a promising feed additive for broilers.
Collapse
Affiliation(s)
- Songwei Han
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
| | - Guowei Xu
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
| | - Kang Zhang
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
| | - Saad Ahmad
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
| | - Lei Wang
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
| | - Fubin Chen
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
| | - Jiahui Liu
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
| | - Xueyan Gu
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
| | - Jianxi Li
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
| | - Jingyan Zhang
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (S.H.)
- Cell Biology and Immunology Group, Wageningen University & Research, 6708 WD Wageningen, The Netherlands
| |
Collapse
|
|
9
|
Qu Z, Zheng Y, Wu S, Bing Y, Sun Z, Zhu S, Li W, Zou X. Two Omics Methods Expose Anti-Depression Mechanism of Raw and Vinegar-Baked Bupleurum Scorzonerifolium Willd. Chem Biodivers 2024; 21:e202301733. [PMID: 38217462 DOI: 10.1002/cbdv.202301733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 01/10/2024] [Accepted: 01/12/2024] [Indexed: 01/15/2024]
Abstract
Bupleurum scorzonerifolium willd. (BS) and its vinegar-baked product (VBS) has been frequently utilized for depression management in clinical Chinese medicine. This paper aims to elucidate the antidepressant mechanism of BS and VBS from the perspectives of metabonomics and gut microbiota. A rat model of depression was established by CUMS combined with feeding alone to evaluate the antidepressant effects of BS and VBS. UPLC-Q-TOF-MS/MS-based metabolomics and 16S rRNA sequencing of rat feces were applied and the correlation of differential metabolic markers and intestinal floras was analyzed. The result revealed that BS and VBS significantly improved depression-like behaviors and the levels of monoamine neurotransmitters in CUMS rats. There were 27 differential endogenous metabolites between CUMS and normal rats, which were involved in 8 metabolic pathways. Whereas, BS and VBS could regulate 18 and 20 metabolites respectively, wherein fifteen of them were shared metabolites. On the genus level, BS and VBS could regulate twenty-five kinds of intestinal floras in CUMS rats, that is, they increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria. In conclusion, both BS and VBS exert excellent antidepressant effects by regulating various metabolic pathways and ameliorating intestinal microflora dysfunction.
Collapse
Affiliation(s)
- Zhongyuan Qu
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Yan Zheng
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Shuang Wu
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Yifan Bing
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Zhiwei Sun
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Shiru Zhu
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Wenlan Li
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
- Engineering Research Center on Natural Antineoplastic Drugs, Ministry of Education, Harbin University of Commerce, Ha Er Bin Shi, 150076, China
| | - Xiang Zou
- Engineering Research Center on Natural Antineoplastic Drugs, Ministry of Education, Harbin University of Commerce, Ha Er Bin Shi, 150076, China
- School of Life Sciences, University of Sussex, Brighton BN19RH, UK
| |
Collapse
|
|
10
|
Zhang PF, Xie D. Targeting the gut microbiota to enhance the antitumor efficacy and attenuate the toxicity of CAR-T cell therapy: a new hope? Front Immunol 2024; 15:1362133. [PMID: 38558812 PMCID: PMC10978602 DOI: 10.3389/fimmu.2024.1362133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 03/05/2024] [Indexed: 04/04/2024] Open
Abstract
Chimeric antigen receptor (CAR) -T cell therapy has achieved tremendous efficacy in the treatment of hematologic malignancies and represents a promising treatment regimen for cancer. Despite the striking response in patients with hematologic malignancies, most patients with solid tumors treated with CAR-T cells have a low response rate and experience major adverse effects, which indicates the need for biomarkers that can predict and improve clinical outcomes with future CAR-T cell treatments. Recently, the role of the gut microbiota in cancer therapy has been established, and growing evidence has suggested that gut microbiota signatures may be harnessed to personally predict therapeutic response or adverse effects in optimizing CAR-T cell therapy. In this review, we discuss current understanding of CAR-T cell therapy and the gut microbiota, and the interplay between the gut microbiota and CAR-T cell therapy. Above all, we highlight potential strategies and challenges in harnessing the gut microbiota as a predictor and modifier of CAR-T cell therapy efficacy while attenuating toxicity.
Collapse
Affiliation(s)
- Peng-Fei Zhang
- Gastric Cancer Center, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Xie
- Department of Medical Genetics, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| |
Collapse
|
|
11
|
Xu R, Feng N, Li Q, Wang H, Li L, Feng X, Su Y, Zhu W. Pectin supplementation accelerates post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential. THE ISME JOURNAL 2024; 18:wrae101. [PMID: 38857378 PMCID: PMC11203915 DOI: 10.1093/ismejo/wrae101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 05/31/2024] [Accepted: 06/09/2024] [Indexed: 06/12/2024]
Abstract
Antibiotic-induced gut dysbiosis (AID) presents a big challenge to host health, and the recovery from this dysbiosis is often slow and incomplete. AID is typically characterized by elevation in redox potential, Enterobacteriaceae load, and aerobic metabolism. In our previous study, a pectin-enriched diet was demonstrated to decrease fecal redox potential and modulate the gut microbiome. Therefore, we propose that pectin supplementation may modulate gut redox potential and favor post-antibiotic gut microbiome reconstitution from dysbiosis. In the present study, rats with AIDwere used to investigate the effects of pectin supplementation on post-antibiotic gut microbiome reconstitution from dysbiosis. The results showed that pectin supplementation accelerated post-antibiotic reconstitution of gut microbiome composition and function and led to enhancement of anabolic reductive metabolism and weakening of catabolic oxidative pathways. These results were corroborated by the measurement of redox potential, findings suggesting that pectin favors post-antibiotic recovery from dysbiosis. Pectin-modulated fecal microbiota transplantation accelerated the decrease in antibiotics-elevated redox potential and Enterobacteriaceae load similarly to pectin supplementation. Moreover, both pectin supplementation and Pectin-modulated fecal microbiota transplantation enriched anaerobic members, primarily from Lachnospiraceae orchestration with enhancement of microbial reductive metabolism in post-antibiotic rats. These findings suggested that pectin supplementation accelerated post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential and that the effect of pectin on redox potential was mediated by remodeling of the intestinal microbiota.
Collapse
Affiliation(s)
- Rongying Xu
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Ni Feng
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Qiuke Li
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Hongyu Wang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Lian Li
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiaobo Feng
- Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210095, China
| | - Yong Su
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Weiyun Zhu
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| |
Collapse
|
|
12
|
Liu Z, Mu C, Zhu W. Metagenomics-based inference of microbial metabolism towards neuroactive amino acids and the response to antibiotics in piglet colon. Amino Acids 2023; 55:1333-1347. [PMID: 37581868 DOI: 10.1007/s00726-023-03311-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 07/30/2023] [Indexed: 08/16/2023]
Abstract
Gut-derived neuroactive metabolites from amino acids perform a broad range of physiological roles in the body. However, the interaction between microbiota and epithelium in the metabolism of amino acids with neuroactive properties remains unclear in the colon of piglets. To investigate the microbial and epithelial metabolism, metagenomics and mucosal metabolomics were performed using colonic samples from 12 ileum-canulated piglets subjected to a 25-day infusion with saline or antibiotics. We categorized 23 metabolites derived from the metabolism of tryptophan, glutamate, and tyrosine, known as precursors of neuroactive metabolites. Microbial enzymes involved in the kynurenine synthesis via arylformamidase, 4-aminobutyric acid (GABA) synthesis via putrescine aminotransferase, and tyramine synthesis via tyrosine decarboxylase were identified in Clostridiales bacterium, uncultured Blautia sp., and Methanobrevibacter wolinii, respectively. Antibiotics significantly affected the microbiota involved in tryptophan-kynurenine and glutamate-GABA metabolism. An increase in the relative abundance of putrescine aminotransferase and Blautia sp. correlated positively with an increase in luminal GABA concentration. Overall, our findings provide new insights into the microbial ability to metabolize key amino acids that are precursors of neuroactive metabolites.
Collapse
Affiliation(s)
- Ziyu Liu
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China
| | - Chunlong Mu
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China.
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
| | - Weiyun Zhu
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China
| |
Collapse
|
|
13
|
Ma LC, Zhao HQ, Wu LB, Cheng ZL, Liu C. Impact of the microbiome on human, animal, and environmental health from a One Health perspective. SCIENCE IN ONE HEALTH 2023; 2:100037. [PMID: 39077043 PMCID: PMC11262275 DOI: 10.1016/j.soh.2023.100037] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 08/21/2023] [Indexed: 07/31/2024]
Abstract
The microbiome encompasses the genomes of the microorganisms that inhabit specific environments. One Health is an emerging concept, recognised as a cohesive, harmonising approach aimed at sustainably improving the well-being of humans, animals, and the environment. The microbiome plays a crucial role in the One Health domain, facilitating interactions among humans, animals, and the environment, along with co-evolution, co-development, co-metabolism, and co-regulation with their associated humans and animals. In addition, the microbiome regulates environmental health through interactions with plant microbiota, which actively participate in substance cycling (particularly the carbon and nitrogen cycles) and influence the overall energy flow in the biosphere. Moreover, antibiotic resistance genes present in microbiota can lead to widespread drug resistance in both humans and animals. This review explores the impact of the microbiome on humans, animals, and the environment, highlighting the significance of focusing on this field in One Health research.
Collapse
Affiliation(s)
- Ling-chao Ma
- School of Global Health, Chinese Centre for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- One Health Centre, Shanghai Jiao Tong University and the University of Edinburgh, Shanghai, China
| | - Han-qing Zhao
- School of Global Health, Chinese Centre for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- One Health Centre, Shanghai Jiao Tong University and the University of Edinburgh, Shanghai, China
| | - Logan Blair Wu
- School of Global Health, Chinese Centre for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- One Health Centre, Shanghai Jiao Tong University and the University of Edinburgh, Shanghai, China
- Population Health & Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, Australia
| | - Zi-le Cheng
- School of Global Health, Chinese Centre for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- One Health Centre, Shanghai Jiao Tong University and the University of Edinburgh, Shanghai, China
| | - Chang Liu
- Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| |
Collapse
|
|
14
|
Liu Y, Wang Y, Li C, Feng H, Liu Y, Ma L. An effective prognostic model in colon adenocarcinoma composed of cuproptosis-related epigenetic regulators. Front Pharmacol 2023; 14:1254918. [PMID: 37701039 PMCID: PMC10494936 DOI: 10.3389/fphar.2023.1254918] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 08/16/2023] [Indexed: 09/14/2023] Open
Abstract
Background: Colorectal adenocarcinoma (COAD) is a common malignant tumor with little effective prognostic markers. Cuproptosis is a newly discovered mode of cell death that may be related to epigenetic regulators. This study aimed to explore the association between epigenetic regulators and cuproptosis, and to establish a prognostic prediction model for COAD based on epigenetic regulators associated with cuproptosis (EACs). Methods: RNA sequencing data and clinical data of 524 COAD patients were obtained from the TCGA-COAD database, cuproptosis-related genes were from the FerrDb database, and epigenetic-related genes were from databases such as GO and EpiFactors. LASSO regression analysis and other methods were used to screen out epigenetic regulators associated with cuproptosis and prognosis. The risk score of each patient was calculated and the patients were divided into high-risk group and low-risk group. Next, the survival difference, functional enrichment analyses, tumor mutation burden, chemotherapy drug sensitivity and other indicators between the two groups were compared and analyzed. Results: We found 716 epigenetic regulators closely related to cuproptosis, among which 35 genes were related to prognosis of COAD. We further screened out 7 EACs from the 35 EACs to construct a prognostic prediction model. We calculated the risk score of each patient based on these 7 genes, and divided the patients into high-risk group and low-risk group. We found that the overall survival rate and progression-free survival rate of the high-risk group were significantly lower than those of the low-risk group. This model showed good predictive ability in the training set, test set and overall data set. We also constructed a prognostic prediction model based on risk score and other clinical features, and drew the corresponding Nomogram. In addition, we found significant differences between the high-risk group and the low-risk group in tumor mutation burden, chemotherapy drug sensitivity and other clinical aspects. Conclusion: We established an effective predictive prediction model for COAD based on EACs, revealing the association between epigenetic regulators and cuproptosis in COAD. We hope that this model can not only facilitate the treatment decision of COAD patients, but also promote the research progress in the field of cuproptosis.
Collapse
Affiliation(s)
- Yang Liu
- Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yizhao Wang
- Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Chang Li
- Department of VIP Unit, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Huijin Feng
- School of Life Sciences, Nanjing University, Nanjing, China
| | - Yanqing Liu
- School of Life Sciences, Nanjing University, Nanjing, China
| | - Lianjun Ma
- Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
15
|
Liu Z, Ling Y, Peng Y, Han S, Ren Y, Jing Y, Fan W, Su Y, Mu C, Zhu W. Regulation of serotonin production by specific microbes from piglet gut. J Anim Sci Biotechnol 2023; 14:111. [PMID: 37542282 PMCID: PMC10403853 DOI: 10.1186/s40104-023-00903-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 06/04/2023] [Indexed: 08/06/2023] Open
Abstract
BACKGROUND Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut. Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models. However, how gut microbes regulate intestinal serotonin production in piglets remains vague. To investigate the relationship between microbiota and serotonin specifically in the colon, microbial composition and serotonin concentration were analyzed in ileum-cannulated piglets subjected to antibiotic infusion from the ileum when comparing with saline infusion. Microbes that correlated positively with serotonin production were isolated from piglet colon and were further used to investigate the regulation mechanisms on serotonin production in IPEC-J2 and a putative enterochromaffin cell line RIN-14B cells. RESULTS Antibiotic infusion increased quantities of Lactobacillus amylovorus (LA) that positively correlated with increased serotonin concentrations in the colon, while no effects observed for Limosilactobacillus reuteri (LR). To understand how microbes regulate serotonin, representative strains of LA, LR, and Streptococcus alactolyticus (SA, enriched in feces from prior observation) were selected for cell culture studies. Compared to the control group, LA, LR and SA supernatants significantly up-regulated tryptophan hydroxylase 1 (TPH1) expression and promoted serotonin production in IPEC-J2 cells, while in RIN-14B cells only LA exerted similar action. To investigate potential mechanisms mediated by microbe-derived molecules, microbial metabolites including lactate, acetate, glutamine, and γ-aminobutyric acid were selected for cell treatment based on computational and metabolite profiling in bacterial supernatant. Among these metabolites, acetate upregulated the expression of free fatty acid receptor 3 and TPH1 while downregulated indoleamine 2,3-dioxygenase 1. Similar effects were also recapitulated when treating the cells with AR420626, an agonist targeting free fatty acid receptor 3. CONCLUSIONS Overall, these results suggest that Lactobacillus amylovorus showed a positive correlation with serotonin production in the pig gut and exhibited a remarkable ability to regulate serotonin production in cell cultures. These findings provide evidence that microbial metabolites mediate the dialogue between microbes and host, which reveals a potential approach using microbial manipulation to regulate intestinal serotonin biosynthesis.
Collapse
Affiliation(s)
- Ziyu Liu
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China
| | - Yidan Ling
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China
| | - Yu Peng
- Hubei CAT Biological Technology Co., Ltd., Wuhan, China
| | - Shuibing Han
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China
| | - Yuting Ren
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China
| | - Yujia Jing
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China
| | - Wenlu Fan
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China
| | - Yong Su
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China
| | - Chunlong Mu
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China.
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
| | - Weiyun Zhu
- Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
- National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China.
| |
Collapse
|
|
16
|
Xu J, Kang Y, Zhong Y, Ye W, Sheng T, Wang Q, Zheng J, Yang Q, Yi P, Li Z. Alteration of gut microbiome and correlated amino acid metabolism are associated with acute myelocytic leukemia carcinogenesis. Cancer Med 2023; 12:16431-16443. [PMID: 37409640 PMCID: PMC10469656 DOI: 10.1002/cam4.6283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 06/08/2023] [Accepted: 06/12/2023] [Indexed: 07/07/2023] Open
Abstract
BACKGROUND The aim of this study is to investigate the profiles of gut microbiota and metabolites in acute myelocytic leukemia (AML) patients treated with/without chemotherapy. METHODS Herein, high-throughput 16S rRNA gene sequencing was performed to analysis gut microbiota profiles, and liquid chromatography and mass spectrometry were performed to analysis metabolites profiles. The correlation between gut microbiota biomarkers identified by LEfSe and differentially expressed metabolites were determined by spearman association analysis. RESULTS The results showed the distinguished gut microbiota and metabolites profiles between AML patients and control individuals or AML patients treated with chemotherapy. Compared to normal populations, the ratio of Firmicutes to Bacteroidetes was increased at the phylum level than that in AML patients, and LEfSe analysis identified Collinsella and Coriobacteriaceae as biomarkers of AML patients. Differential metabolite analysis indicated that, compared to AML patients, numerous differential amino acids and analogs could be observed in control individuals and AML patients treated with chemotherapy. Interestingly, spearman association analysis demonstrated that plenty of bacteria biomarkers shows statistical correlations with differentially expressed amino acid metabolites. In addition, we found that both Collinsella and Coriobacteriaceae demonstrate remarkable positive correlation with hydroxyprolyl-hydroxyproline, prolyl-tyrosine, and tyrosyl-proline. CONCLUSION In conclusion, our present study investigated the role of the gut-microbiome-metabolome axis in AML and revealed the possibility of AML treatment by gut-microbiome-metabolome axis in the further.
Collapse
Affiliation(s)
- Jing Xu
- Department of HematologyThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| | - Yong Kang
- Department of HematologyThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
- Department of HematologyFirst Affiliated Hospital of Gannan Medical UniversityGanzhouChina
| | - Yan Zhong
- Department of HematologyThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
- Department of General MedicineGanzhou People's hospitalGanzhouChina
| | - Wencan Ye
- Department of HematologyThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
- Department of HematologyFirst Affiliated Hospital of Gannan Medical UniversityGanzhouChina
| | - Tianle Sheng
- Department of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| | - Qingming Wang
- Department of HematologyThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| | - Jifu Zheng
- Department of HematologyThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| | - Qiuyue Yang
- Department of Scientific Research ProjectWuhan Kindstar Medical Laboratory Co., Ltd.WuhanChina
- Kindstar Global Precision Medicine InstituteWuhanChina
| | - Ping Yi
- Department of Scientific Research ProjectWuhan Kindstar Medical Laboratory Co., Ltd.WuhanChina
- Kindstar Global Precision Medicine InstituteWuhanChina
| | - Zhenjiang Li
- Department of HematologyThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| |
Collapse
|
|
17
|
Fu C, Ni J, Huang R, Gao Y, Li S, Li Y, JinjinLi, Zhong K, Zhang P. Sex different effect of antibiotic and probiotic treatment on intestinal microbiota composition in chemically induced liver injury rats. Genomics 2023; 115:110647. [PMID: 37217087 DOI: 10.1016/j.ygeno.2023.110647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 04/10/2023] [Accepted: 05/19/2023] [Indexed: 05/24/2023]
Abstract
Differences in the gut microbiota and metabolic processes between males and females may explain differences in the risk of liver injury; however, the sex-specific effects of antibiotics and probiotics on these relationships are not clear. We evaluated differences in the gut microbiota and the risk of liver injury between male and female rats after the oral administration of antibiotics or probiotics followed by a period of diethylnitrosamine treatment to chemically induce liver injuryusing high-throughput sequencing of fecal microbiota combined with histological analyses of liver and colon tissues. Our results suggest that the ratio of gram-positive to gram-negative bacteria in kanamycin-treated rats was significantly higher than that of other groups, and this difference persisted for the duration of the experiment. Antibiotics significantly changed the composition of the gut microbiota of experimental rats. Clindamycin caused more diethylnitrosamine-induced damage to livers of male rats. Probiotics did not influencethe gut microbiota; however, they hadprotective effects against liver injury induced by diethylnitrosamine, especially in female rats. These results strengthen our understanding of sex differences in the indirect effects of antibiotics or probiotics on metabolism and liver injury in hosts via the gut microbiota.
Collapse
Affiliation(s)
- Chaoyi Fu
- General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Jiajia Ni
- General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China; Research and Development Center, Guangdong Meilikang Bio-Sciences Ltd., Foshan 528200, China; Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Medical University, Dongguan 523808, China.
| | - Rong Huang
- Department of Neonatal Surgery, Guangdong Women and Children Hospital, Guangzhou 511400, China
| | - Yi Gao
- General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China.
| | - Shao Li
- General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Yang Li
- General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - JinjinLi
- School of Life Sciences, Qilu Normal University, Jinan 250200, China
| | - Kebo Zhong
- General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Peng Zhang
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| |
Collapse
|
|
18
|
Yu Y, Lin X, Feng F, Wei Y, Wei S, Gong Y, Guo C, Wang Q, Shuai P, Wang T, Qin H, Li G, Yi L. Gut microbiota and ionizing radiation-induced damage: Is there a link? ENVIRONMENTAL RESEARCH 2023; 229:115947. [PMID: 37080277 DOI: 10.1016/j.envres.2023.115947] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 04/14/2023] [Accepted: 04/17/2023] [Indexed: 05/03/2023]
Abstract
According to observational findings, ionizing radiation (IR) triggers dysbiosis of the intestinal microbiota, affecting the structural composition, function, and species of the gut microbiome and its metabolites. These modifications can further exacerbate IR-induced damage and amplify proinflammatory immune responses. Conversely, commensal bacteria and favorable metabolites can remodel the IR-disturbed gut microbial structure, promote a balance between anti-inflammatory and proinflammatory mechanisms in the body, and mitigate IR toxicity. The discovery of effective and safe remedies to prevent and treat radiation-induced injuries is vitally needed because of the proliferation of radiation toxicity threats produced by recent radiological public health disasters and increasing medical exposures. This review examines how the gut microbiota and its metabolites are linked to the processes of IR-induced harm. We highlight protective measures based on interventions with gut microbes to optimize the distress caused by IR damage to human health. We offer prospects for research in emerging and promising areas targeting the prevention and treatment of IR-induced damage.
Collapse
Affiliation(s)
- Yueqiu Yu
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Xiang Lin
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Feiyang Feng
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Yuanyun Wei
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Shuang Wei
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Yaqi Gong
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Caimao Guo
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Qingyu Wang
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Peimeng Shuai
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Tiantian Wang
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Hui Qin
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Guoqing Li
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
| | - Lan Yi
- Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
| |
Collapse
|
|
19
|
Alagna L, Mancabelli L, Magni F, Chatenoud L, Bassi G, Del Bianco S, Fumagalli R, Turroni F, Mangioni D, Migliorino GM, Milani C, Muscatello A, Nattino G, Picetti E, Pinciroli R, Rossi S, Tonetti T, Vargiolu A, Bandera A, Ventura M, Citerio G, Gori A. Changes in upper airways microbiota in ventilator-associated pneumonia. Intensive Care Med Exp 2023; 11:17. [PMID: 36862343 PMCID: PMC9981834 DOI: 10.1186/s40635-023-00496-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 02/03/2023] [Indexed: 03/03/2023] Open
Abstract
BACKGROUND The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. METHODS Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). RESULTS Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value < 0.012). Furthermore, an overall decrease in microbial diversity was observed in both groups at T3 as compared to T0. At T3, a loss of some genera (Prevotella 7, Fusobacterium, Neisseria, Escherichia-Shigella and Haemophilus) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP. CONCLUSIONS In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP.
Collapse
Affiliation(s)
- Laura Alagna
- Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Leonardo Mancabelli
- grid.10383.390000 0004 1758 0937Department of Medicine and Surgery, University of Parma, Parma, Italy ,grid.10383.390000 0004 1758 0937Interdepartmental Research Centre Microbiome Research Hub, University of Parma, Parma, Italy
| | - Federico Magni
- grid.415025.70000 0004 1756 8604Neurointensive Care Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Liliane Chatenoud
- grid.4527.40000000106678902Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | | | - Silvia Del Bianco
- grid.415025.70000 0004 1756 8604Neurointensive Care Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Roberto Fumagalli
- grid.7563.70000 0001 2174 1754School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Francesca Turroni
- grid.10383.390000 0004 1758 0937Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy ,grid.10383.390000 0004 1758 0937Interdepartmental Research Centre Microbiome Research Hub, University of Parma, Parma, Italy
| | - Davide Mangioni
- grid.414818.00000 0004 1757 8749Present Address: Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy ,grid.4708.b0000 0004 1757 2822Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Guglielmo M. Migliorino
- grid.415025.70000 0004 1756 8604Infectious Diseases Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Christian Milani
- grid.10383.390000 0004 1758 0937Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy ,grid.10383.390000 0004 1758 0937Interdepartmental Research Centre Microbiome Research Hub, University of Parma, Parma, Italy
| | - Antonio Muscatello
- grid.414818.00000 0004 1757 8749Present Address: Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giovanni Nattino
- grid.4527.40000000106678902Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Edoardo Picetti
- grid.411482.aDepartment of Anesthesia and Intensive Care, Parma University Hospital, Parma, Italy
| | - Riccardo Pinciroli
- grid.7563.70000 0001 2174 1754School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Sandra Rossi
- grid.411482.aDepartment of Anesthesia and Intensive Care, Parma University Hospital, Parma, Italy
| | - Tommaso Tonetti
- grid.411482.aDepartment of Anesthesia and Intensive Care, Parma University Hospital, Parma, Italy
| | - Alessia Vargiolu
- grid.415025.70000 0004 1756 8604Neurointensive Care Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy ,grid.7563.70000 0001 2174 1754School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Alessandra Bandera
- grid.414818.00000 0004 1757 8749Present Address: Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy ,grid.4708.b0000 0004 1757 2822Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Marco Ventura
- grid.10383.390000 0004 1758 0937Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy ,grid.10383.390000 0004 1758 0937Interdepartmental Research Centre Microbiome Research Hub, University of Parma, Parma, Italy
| | - Giuseppe Citerio
- grid.415025.70000 0004 1756 8604Neurointensive Care Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy ,grid.7563.70000 0001 2174 1754School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Andrea Gori
- grid.414818.00000 0004 1757 8749Present Address: Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy ,grid.4708.b0000 0004 1757 2822Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| |
Collapse
|
|
20
|
Murali A, Zickgraf FM, Ternes P, Giri V, Cameron HJ, Sperber S, Haake V, Driemert P, Kamp H, Weyer DF, Sturla SJ, Rietjens IMGM, van Ravenzwaay B. Gut Microbiota as Well as Metabolomes of Wistar Rats Recover within Two Weeks after Doripenem Antibiotic Treatment. Microorganisms 2023; 11:microorganisms11020533. [PMID: 36838498 PMCID: PMC9959319 DOI: 10.3390/microorganisms11020533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/10/2023] [Accepted: 02/17/2023] [Indexed: 02/22/2023] Open
Abstract
An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies.
Collapse
Affiliation(s)
- Aishwarya Murali
- BASF SE, 67056 Ludwigshafen, Germany
- Correspondence: (A.M.); (B.v.R.)
| | | | | | | | | | | | - Volker Haake
- BASF Metabolome Solutions GmbH, 10589 Berlin, Germany
| | | | - Hennicke Kamp
- BASF Metabolome Solutions GmbH, 10589 Berlin, Germany
| | | | - Shana J. Sturla
- ETH Zürich, Department of Health Sciences and Technology, Schmelzbergstrasse 9, 8092 Zurich, Switzerland
| | | | - Bennard van Ravenzwaay
- Department of Toxicology, Wageningen University & Research, 6703 HE Wageningen, The Netherlands
- Correspondence: (A.M.); (B.v.R.)
| |
Collapse
|
|
21
|
Liang S, Wang L, Wu X, Hu X, Wang T, Jin F. The different trends in the burden of neurological and mental disorders following dietary transition in China, the USA, and the world: An extension analysis for the Global Burden of Disease Study 2019. Front Nutr 2023; 9:957688. [PMID: 36698474 PMCID: PMC9869872 DOI: 10.3389/fnut.2022.957688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 12/06/2022] [Indexed: 01/12/2023] Open
Abstract
Introduction The highly processed western diet is substituting the low-processed traditional diet in the last decades globally. Increasing research found that a diet with poor quality such as western diet disrupts gut microbiota and increases the susceptibility to various neurological and mental disorders, while a balanced diet regulates gut microbiota and prevents and alleviates the neurological and mental disorders. Yet, there is limited research on the association between the disease burden expanding of neurological and mental disorders with a dietary transition. Methods We compared the disability-adjusted life-years (DALYs) trend by age for neurological and mental disorders in China, in the United States of America (USA), and across the world from 1990 to 2019, evaluated the dietary transition in the past 60 years, and analyzed the association between the burden trend of the two disorders with the changes in diet composition and food production. Results We identified an age-related upward pattern in disease burden in China. Compared with the USA and the world, the Chinese neurological and mental disorders DALY percent was least in the generation over 75 but rapidly increased in younger generations and surpassed the USA and/or the world in the last decades. The age-related upward pattern in Chinese disease burdens had not only shown in the presence of cardiovascular diseases, neoplasms, and diabetes mellitus but also appeared in the presence of depressive disorders, Parkinson's disease, Alzheimer's disease and other dementias, schizophrenia, headache disorders, anxiety disorders, conduct disorders, autism spectrum disorders, and eating disorders, successively. Additionally, the upward trend was associated with the dramatic dietary transition including a reduction in dietary quality and food production sustainability, during which the younger generation is more affected than the older. Following the increase in total calorie intake, alcohol intake, ratios of animal to vegetal foods, and poultry meat to pulses, the burdens of the above diseases continuously rose. Then, following the rise of the ratios of meat to pulses, eggs to pulses, and pork to pulses, the usage of fertilizers, the farming density of pigs, and the burdens of the above disease except diabetes mellitus were also ever-increasing. Even the usage of pesticides was positively correlated with the burdens of Parkinson's disease, schizophrenia, cardiovascular diseases, and neoplasms. Contrary to China, the corresponding burdens of the USA trended to reduce with the improvements in diet quality and food production sustainability. Discussion Our results suggest that improving diet quality and food production sustainability might be a promising way to stop the expanding burdens of neurological and mental disorders.
Collapse
Affiliation(s)
- Shan Liang
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Gut-brain Psychology Laboratory, Beijing, China
| | - Li Wang
- Department for the History of Science and Scientific Archaeology, University of Science and Technology of China, Hefei, Anhui, China
| | - Xiaoli Wu
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Gut-brain Psychology Laboratory, Beijing, China
| | - Xu Hu
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Gut-brain Psychology Laboratory, Beijing, China
| | - Tao Wang
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Gut-brain Psychology Laboratory, Beijing, China
| | - Feng Jin
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Gut-brain Psychology Laboratory, Beijing, China
| |
Collapse
|
|
22
|
Abstract
This study was conducted to investigate the effects of high-altitude hypoxic environments on the gut microbiota. Male Sprague-Dawley rats were randomly divided into three groups, namely, the plain, moderate-altitude hypoxic, and high-altitude hypoxic groups. On the 3rd, 7th, 15th, and 30th days of exposure, fecal samples were collected and analyzed via 16S rRNA gene sequencing technology. Fecal microbiota transplantation (FMT) experiments were also performed. The results showed significant differences between the gut microbiota structure and diversity of rats in the high-altitude hypoxic group and those of rats in the other groups. Further, compared with that of rats in the plain group, the gut microbiota of rats in the two hypoxic groups showed the most significant changes on day 7. Furthermore, the gut microbiota of the rats in the FMT groups exhibited changes and became increasingly similar to those of the rats in the hypoxic groups. We also identified the phylum Firmicutes, genus Akkermansia, and genus Lactobacillus as the core microbiota under hypoxic conditions. Phenotypic analysis indicated a decrease in the proportion of aerobic bacteria and an increase in that of anaerobic bacteria, possibly owing to the high-altitude hypoxic environment. Additionally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including carbohydrate metabolism, energy metabolism, glycan biosynthesis, and metabolism. These findings indicated significant changes in gut microbiota structure and diversity under high-altitude hypoxia, establishing a foundation for further research on the pathogenesis and development of diseases, as well as drug metabolism, under high-altitude hypoxia. IMPORTANCE In this study, we investigated the effects of high-altitude hypoxic environments with low oxygen levels on the gut microbiota characteristics of rats. We observed that high-altitude hypoxia is an important environmental factor that can affect gut microbiota structure and diversity, thereby affecting homeostasis in the host intestinal environment. These findings provide a basis for further studies on disease initiation and development, as well as drug metabolism, in high-altitude hypoxic environments.
Collapse
|
|
23
|
Li H, Li N, Lu Q, Yang J, Zhao J, Zhu Q, Yi S, Fu W, Luo T, Tang J, Zhang Y, Yang G, Liu Z, Xu J, Chen W, Zhu J. Chronic alcohol-induced dysbiosis of the gut microbiota and gut metabolites impairs sperm quality in mice. Front Microbiol 2022; 13:1042923. [PMID: 36532416 PMCID: PMC9751024 DOI: 10.3389/fmicb.2022.1042923] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 11/04/2022] [Indexed: 08/23/2023] Open
Abstract
Studies have indicated that the ethanol exposure impairs the gut microbiota, At the same time, high levels of alcohol exposure damage sperm in mice. However, whether the gut microbiota is involved in mediating the effects of alcohol on sperm quality remains unclear. This study aimed to assess the effect of chronic alcohol consumption on intestinal microbiota in mice and analyze the potential pathophysiological effect of altered intestinal microbiota on sperm quality. We established a mouse model of chronic alcohol consumption by allowing male C57 mice to freely ingest 10% ethanol for 10 weeks, and collected the fecal microbiota of the male mice in the chronic drinking group (alcohol) and the control group (control) and transplanted the specimens into the transplant groups (the alcohol-fecal microbiota transplantation [FMT] group and the control-FMT group). Sperm quality was significantly decreased in the alcohol-FMT group compared with the control-FMT group. Gut microbiota analysis revealed that the abundance of 11 operational taxonomic units (OTUs) was altered in the alcohol-FMT group. Nontargeted metabolomics identified 105 differentially altered metabolites, which were mainly annotated to amino acids, lipids, glycerophosphoethanolamine, organic oxygenic compounds, organic acids and their derivatives, steroids, and flavonoids. In particular, the oxidative phosphorylation pathway, which is the key to spermatogenesis, was significantly enriched in the alcohol-FMT group. Moreover, compared with the control-FMT group, the alcohol-FMT group presented significantly higher serum endotoxin and inflammatory cytokine levels, with more pronounced T cell and macrophage infiltration in the intestinal lamina propria and elevated levels of testicular inflammatory cytokines. In addition, RNA sequencing showed significant differences in the expression of testis-related genes between the alcohol-FMT group and the control-FMT group. In particular, the expression of genes involved in gamete meiosis, testicular mitochondrial function, and the cell division cycle was significantly reduced in alcohol-FMT mice. In conclusion, these findings indicated that intestinal dysbiosis induced by chronic alcohol consumption may be an important factor contributing to impaired sperm quality. Chronic alcohol consumption induces intestinal dysbiosis, which then leads to metabolic disorders, elevated serum endotoxin and inflammatory cytokine levels, testicular inflammation, abnormal expression of related genes, and ultimately, impaired sperm quality. These findings are potentially useful for the treatment of male infertility.
Collapse
Affiliation(s)
- Hui Li
- Department of Ultrasound, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Ningshan Li
- Department of Ultrasound, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Qudong Lu
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Jun Yang
- Department of Ultrasound, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Jiang Zhao
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Qiong Zhu
- Department of Ultrasound, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Shanhong Yi
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Weihua Fu
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Tingting Luo
- Department of Ultrasound, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Jiawei Tang
- Department of Ultrasound, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Yi Zhang
- Department of Ultrasound, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Guoliang Yang
- Department of Ultrasound, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Zheng Liu
- Department of Ultrasound, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Jie Xu
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Wei Chen
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Jingzhen Zhu
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| |
Collapse
|
|
24
|
Tims S, Marsaux C, Pinto A, Daly A, Karall D, Kuhn M, Santra S, Roeselers G, Knol J, MacDonald A, Scholl-Bürgi S. Altered gut microbiome diversity and function in patients with propionic acidemia. Mol Genet Metab 2022; 137:308-322. [PMID: 36274442 DOI: 10.1016/j.ymgme.2022.09.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 09/30/2022] [Accepted: 09/30/2022] [Indexed: 11/30/2022]
Abstract
Propionic acidemia (PA) is an inherited metabolic disorder of propionate metabolism, where the gut microbiota may play a role in pathophysiology and therefore, represent a relevant therapeutic target. Little is known about the gut microbiota composition and activity in patients with PA. Although clinical practice varies between metabolic treatment centers, management of PA requires combined dietary and pharmaceutical treatments, both known to affect the gut microbiota. This study aimed to characterize the gut microbiota and its metabolites in fecal samples of patients with PA compared with healthy controls from the same household. Eight patients (aged 3-14y) and 8 controls (4-31y) were recruited from Center 1 (UK) and 7 patients (11-33y) and 6 controls (15-54y) from Center 2 (Austria). Stool samples were collected 4 times over 3 months, alongside data on dietary intakes and medication usage. Several microbial taxa differed between patients with PA and controls, particularly for Center 1, e.g., Proteobacteria levels were increased, whereas butyrate-producing genera, such as Roseburia and Faecalibacterium, were decreased. Most measured microbial metabolites were lower in patients with PA, and butyrate was particularly depleted in patients from Center 1. Furthermore, microbiota profile of these patients showed the lowest compositional and functional diversity, and lowest stability over 3 months. As the first study to map the gut microbiota of patients with PA, this work represents an important step forward for developing new therapeutic strategies to further improve PA clinical status. New dietary strategies should consider microbial propionate production as well as butyrate production and microbiota stability.
Collapse
Affiliation(s)
- Sebastian Tims
- Danone Nutricia Research, Uppsalalaan 12, 3584CT Utrecht, the Netherlands.
| | - Cyril Marsaux
- Danone Nutricia Research, Uppsalalaan 12, 3584CT Utrecht, the Netherlands.
| | - Alex Pinto
- Department of Dietetics, Birmingham Women's and Children's NHS Foundation Trust, Steelhouse Lane, Birmingham B4 6NH, UK.
| | - Anne Daly
- Department of Dietetics, Birmingham Women's and Children's NHS Foundation Trust, Steelhouse Lane, Birmingham B4 6NH, UK.
| | - Daniela Karall
- Department of Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.
| | - Mirjam Kuhn
- Danone Nutricia Research, Uppsalalaan 12, 3584CT Utrecht, the Netherlands.
| | - Saikat Santra
- Department of Clinical Inherited Metabolic Disorders, Birmingham Women's and Children's NHS Foundation Trust, Steelhouse Lane, Birmingham B4 6NH, UK.
| | - Guus Roeselers
- Danone Nutricia Research, Uppsalalaan 12, 3584CT Utrecht, the Netherlands.
| | - Jan Knol
- Danone Nutricia Research, Uppsalalaan 12, 3584CT Utrecht, the Netherlands; Department of Agrotechnology and Food Sciences, Wageningen University, Stippeneng 4, 6708WE Wageningen, the Netherlands.
| | - Anita MacDonald
- Department of Dietetics, Birmingham Women's and Children's NHS Foundation Trust, Steelhouse Lane, Birmingham B4 6NH, UK.
| | - Sabine Scholl-Bürgi
- Department of Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.
| |
Collapse
|
|
25
|
Long-term chemically protected sodium butyrate supplementation in broilers as an antibiotic alternative to dynamically modulate gut microbiota. Poult Sci 2022; 101:102221. [PMCID: PMC9630789 DOI: 10.1016/j.psj.2022.102221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 09/28/2022] [Accepted: 09/29/2022] [Indexed: 11/06/2022] Open
Abstract
Chemically protected sodium butyrate (CSB) is a new kind of sodium butyrate. Our previous study found that 1,000 mg/kg of CSB had the potential capacity of improving growth performance and promoting early development of small intestine in broilers. This study aimed to investigate the effect of long-term antibiotics or CSB supplementation for intestinal microflora dynamical regulation in broilers. One hundred ninety-two 1-day-old Arbor Acres male broilers were randomly allocated into 3 dietary treatment (8 replicates per treatment) and fed with a basal diet (CON), a diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg) (ANT), or a diet supplemented with 1,000 mg/kg of CSB, respectively. Results showed that dietary supplementation of CSB or ANT treatment elevated the weight gain and feed conversion ratio (FCR; P < 0.05), as compared with control (CON) group. Additionally, CON, CSB, or ANT administration dynamically altered the gut microbiota composition as time goes on. The increased presence of potential pathogens, such as Romboutsia and Shuttleworthia, and decreased beneficial bacteria such as Alistipes, Akkermansia, and Bacteroides were verified in new gut homeostasis reshaped by long-term antibiotics treatment, which has adverse effects on intestinal development and health of broilers. Conversely, CSB supplementation could dynamically enhance the relative abundance of Bacteroides, and decrease Romboutsia and Shuttleworthia in new microflora, which has positive effects on intestinal bacteria of broilers compared with CON group. Meanwhile, CSB supplementation was significantly increased the concentration of propionic acid and total short chain fatty acids (total SCFA; P < 0.05) in comparison with CON and ANT groups. Moreover, CSB treatment significantly increased anti-inflammatory and antioxidative capacities (P < 0.05) of broilers compared with ANT group. Taken together, we revealed characteristic structural changes of gut microbiota throughout long-term CSB or ANT supplementation in broilers, which provided a basic data for evaluating the mechanism of action affecting intestinal health by CSB or ANT administration and CSB as an alternative to antibiotics in the broilers industry.
Collapse
|
|
26
|
Bai X, Yang J, Liu G, Zhu J, Wang Q, Gu W, La L, Li X. Regulation of CYP450 and drug transporter mediated by gut microbiota under high-altitude hypoxia. Front Pharmacol 2022; 13:977370. [PMID: 36188572 PMCID: PMC9520702 DOI: 10.3389/fphar.2022.977370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 08/26/2022] [Indexed: 11/17/2022] Open
Abstract
Hypoxia, an essential feature of high-altitude environments, has a significant effect on drug metabolism. The hypoxia–gut microbiota–CYP450/drug transporter axis is emerging as a vital factor in drug metabolism. However, the mechanisms through which the gut microbiota mediates the regulation of CYP450/drug transporters under high-altitude hypoxia have not been well defined. In this study, we investigated the mechanisms underlying gut microbial changes in response to hypoxia. We compared 16S ribosomal RNA gene sequences of the gut microbiota from plain and hypoxic rats. As a result, we observed an altered gut microbial diversity and composition in rats under hypoxia. Our findings show that dysregulated gut microbiota changes CYP3A1 and MDR1 expressions in high-altitude hypoxic environments. Thus, our study reveals a novel mechanism underlying the functioning of the hypoxia–gut microbiota–CYP450/drug transporter axis.
Collapse
Affiliation(s)
- Xue Bai
- Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China
| | - Jianxin Yang
- Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China
| | - Guiqin Liu
- Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China
| | - Junbo Zhu
- Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China
| | - Qian Wang
- Medical College, Qinghai University Medical College, Xining, China
| | - Wenqi Gu
- Medical College, Qinghai University Medical College, Xining, China
| | - Linli La
- Medical College, Qinghai University Medical College, Xining, China
| | - Xiangyang Li
- Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China
- *Correspondence: Xiangyang Li,
| |
Collapse
|
|
27
|
Lee MS, Sulit A, Frizelle F, Purcell R. The microbiome in adult acute appendicitis. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2022; 3:e8. [PMID: 39295777 PMCID: PMC11406380 DOI: 10.1017/gmb.2022.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 06/06/2022] [Accepted: 07/26/2022] [Indexed: 09/21/2024]
Abstract
Acute appendicitis is a common acute surgical emergency; however, the pathogenesis of adult appendicitis remains poorly understood. The microbiome is increasingly thought to play a key role in inflammatory disease of the bowel and similarly, may play a role in appendicitis. This study aimed to characterise the microbiome of adult acute appendicitis in a prospective cohort. We recruited 60 adults with acute appendicitis and 20 healthy controls. Rectal swabs were taken from each patient. After DNA extraction, 16S rRNA amplicon sequencing was carried out for analysis of diversity and taxonomic abundance. Phylogenetic sequencing of the samples indicated that there is a difference between the microbial composition of those with acute appendicitis and healthy controls, with a statistically significant decrease in alpha diversity in rectal swabs of appendicitis patients compared to healthy controls. At the genus level, we saw an increased abundance of potential pathogens, for example, Parvimonas and Acinetobacter, and a decrease in commensal taxa such as Faecalibacterium, Blautia and Lachnospiraceae in appendicitis patients compared to healthy controls. There was a reduction in diversity and loss of commensals in the microbiome of those with acute appendicitis, which may play a role in the cascade leading to acute appendicitis or the result of this.
Collapse
Affiliation(s)
- Mei Sze Lee
- Department of Surgery, University of Otago, Christchurch, New Zealand
- Department of General Surgery, Christchurch, New Zealand
| | - Arielle Sulit
- Department of Surgery, University of Otago, Christchurch, New Zealand
- Massey University, Auckland, New Zealand
| | - Frank Frizelle
- Department of Surgery, University of Otago, Christchurch, New Zealand
- Department of General Surgery, Christchurch, New Zealand
| | - Rachel Purcell
- Department of Surgery, University of Otago, Christchurch, New Zealand
| |
Collapse
|
|
28
|
Abstract
Neonatal infections remain an important cause of neonatal morbidity and mortality worldwide. Neonatal sepsis is a systemic infection that can be classified as early-onset or late-onset pending the timing of presentation. The pathophysiology and causative pathogens of neonatal sepsis vary, with early-onset sepsis being associated with a vertically transmitted infection from mother to neonate versus late onset sepsis being commonly associated with nosocomial infections. The signs and symptoms of neonatal sepsis mimic those associated with prematurity, making timely diagnosis difficult for treating clinicians. The management of neonatal sepsis is centered around obtaining adequate culture data and initiation of broad-spectrum parenteral antibiotics. Controversies surrounding the management of neonatal sepsis include the administration of empiric antibiotics, given recent clinical studies associating early antibiotic use with clinical sequelae such as late-onset sepsis, necrotizing enterocolitis, and death in the preterm, low-birthweight infant population.
Collapse
Affiliation(s)
- Elizabeth Pace
- University of Pittsburgh, Department of Surgery, Pittsburgh, PA, United States.
| | - Toby Yanowitz
- University of Pittsburgh, Department of Neonatology, Pittsburgh, PA, United States
| |
Collapse
|
|
29
|
Chen X, Liu Y, Yao H, Song W, Song Y, Gu J, Guo Y. Antibiotics-induced disruption of gut microbiota increases systemic exposure of clopidogrel active metabolite in type 2 diabetic rats. Drug Metab Dispos 2022; 50:DMD-AR-2022-000906. [PMID: 35858690 DOI: 10.1124/dmd.122.000906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/10/2022] [Accepted: 05/31/2022] [Indexed: 11/22/2022] Open
Abstract
Gut microbiota play an important role in the pathophysiology of type 2 diabetic mellitus (T2DM) and biodisposition of drugs. Our previous study demonstrated that T2DM rats had the decreased plasma exposure of clopidogrel active metabolite (Clop-AM) due to upregulation of P-glycoprotein (P-gp). However, whether the change to clopidogrel (Clop) disposition under T2DM condition is associated with gut microbiota needs to be elucidated. In the study, we used an antibiotic cocktail consisting of ampicillin, vancomycin, metronidazole, and neomycin to disrupt gut microbiota and observed their influence on pharmacokinetic profiles of Clop-AM. Antibiotic administration markedly alleviated T2DM rats' phenotype including hyperglycemia, insulin resistance, oxidative stress, inflammation, hyperlipidemia, and liver dysfunction. Meanwhile, treatment with antibiotics significantly reversed the reduced systemic exposure of Clop-AM in T2DM rats relative to control rats, which was associated with the decreased intestinal P-gp level that might promote Clop absorption, resulting in more Clop transformation to Clop-AM. Fecal microbiome analysis exhibited a serious disruption of gut microbiota after antibiotic treatment with the sharply reduced microbial load and the altered microbial composition. Interestingly, an in vitro study showed that antibiotics had no influence on P-gp mRNA leve in SW480 cells, suggesting the microbiome disruption, not the direct role of antibiotics on P-gp expression, contributes to the altered P-gp level and Clop disposition in T2DM rats. The findings add new insights into the potential impact of gut microbiota on Clop biodisposition. Significance Statement 1.Antibiotics increase systemic exposure of Clop-AM in T2DM rats, which is associated with the downregulation of P-gp level.2.Antibiotics-induced disruption of gut microbiota, not direct effect of antibiotics on P-gp and CYPs expression, contributes to the altered Clop disposition.3.Antibiotics also alleviate T2DM phenotype including hyperglycemia, hyperlipidemia, insulin resistance, liver dysfunction and inflammation.
Collapse
Affiliation(s)
| | | | | | | | - Yu Song
- Hainan Tropical Ocean University, China
| | | | - Yingjie Guo
- School of Life Sciences, Jilin university china, China
| |
Collapse
|
|
30
|
Luo Y, Chen L, Lu Z, Zhang W, Liu W, Chen Y, Wang X, Du W, Luo J, Wu H. Genome sequencing of biocontrol strain Bacillus amyloliquefaciens Bam1 and further analysis of its heavy metal resistance mechanism. BIORESOUR BIOPROCESS 2022; 9:74. [PMID: 38647608 PMCID: PMC10991351 DOI: 10.1186/s40643-022-00563-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Accepted: 07/01/2022] [Indexed: 11/10/2022] Open
Abstract
Plant growth-promoting rhizobacteria (PGPR) or Biocontrol strains inevitably encounter heavy metal excess stress during the product's processing and application. Bacillus amyloliquefaciens Bam1 was a potential biocontrol strain with strong heavy metal resistant ability. To understand its heavy metal resistance mechanism, the complete genome of Bam1 had been sequenced, and the comparative genomic analysis of Bam1 and FZB42, an industrialized PGPR and biocontrol strain with relatively lower heavy metal tolerance, was conducted. The comparative genomic analysis of Bam1 and the other nine B. amyloliquefaciens strains as well as one Bacillus velezensis (genetically and physiologically very close to B. amyloliquefaciens) was also performed. Our results showed that the complete genome size of Bam1 was 3.95 Mb, 4219 coding sequences were predicted, and it possessed the highest number of unique genes among the eleven analyzed strains. Nine genes related to heavy metal resistance were detected within the twelve DNA islands of Bam1, while only two of them were detected within the seventeen DNA islands of FZB42. When compared with B. amyloliquefaciens type strain DSM7, Bam1 lacked contig L, whereas FZB42 lacked contig D and I, as well as just possessed contig B with a very small size. Our results could also deduce that Bam1 promoted its essential heavy metal resistance mainly by decreasing the import and increasing the export of heavy metals with the corresponding homeostasis systems, which are regulated by different metalloregulators. While Bam1 promoted its non-essential heavy metal resistance mainly by the activation of some specific or non-specific exporters responding to different heavy metals. The variation of the genes related to heavy metal resistance and the other differences of the genomes, including the different number and arrangement of contigs, as well as the number of the heavy metal resistant genes in Prophages and Genomic islands, led to the significant different resistance of Bam1 and FZB42 to heavy metals.
Collapse
Affiliation(s)
- Yuanchan Luo
- Department of Applied Biology, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
| | - Lei Chen
- Department of Plant Quarantine, Shanghai Extension and Service Center of Agriculture Technology, Shanghai, 201103, China
| | - Zhibo Lu
- Department of Applied Biology, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
| | - Weijian Zhang
- Department of Applied Biology, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
| | - Wentong Liu
- Department of Applied Biology, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
| | - Yuwei Chen
- Department of Applied Biology, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
| | - Xinran Wang
- Department of Applied Biology, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
| | - Wei Du
- Agricultural Technology Extension Station of Ningxia, 2, West Shanghai Road, Yinchuan, 750001, China
| | - Jinyan Luo
- Department of Plant Quarantine, Shanghai Extension and Service Center of Agriculture Technology, Shanghai, 201103, China.
| | - Hui Wu
- Department of Applied Biology, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
- State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
- Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai, 200237, China.
- Key Laboratory of Bio-Based Material Engineering of China National Light Industry Council, 130 Meilong Road, Shanghai, 200237, China.
| |
Collapse
|
|
31
|
The Role of Gut Microbiota in the Skeletal Muscle Development and Fat Deposition in Pigs. Antibiotics (Basel) 2022; 11:antibiotics11060793. [PMID: 35740199 PMCID: PMC9220283 DOI: 10.3390/antibiotics11060793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 06/07/2022] [Accepted: 06/08/2022] [Indexed: 12/02/2022] Open
Abstract
Pork quality is a factor increasingly considered in consumer preferences for pork. The formation mechanisms determining meat quality are complicated, including endogenous and exogenous factors. Despite a lot of research on meat quality, unexpected variation in meat quality is still a major problem in the meat industry. Currently, gut microbiota and their metabolites have attracted increased attention in the animal breeding industry, and recent research demonstrated their significance in muscle fiber development and fat deposition. The purpose of this paper is to summarize the research on the effects of gut microbiota on pig muscle and fat deposition. The factors affecting gut microbiota composition will also be discussed, including host genetics, dietary composition, antibiotics, prebiotics, and probiotics. We provide an overall understanding of the relationship between gut microbiota and meat quality in pigs, and how manipulation of gut microbiota may contribute to increasing pork quality for human consumption.
Collapse
|
|
32
|
Morowitz MJ, Katheria AC, Polin RA, Pace E, Huang DT, Chang CCH, Yabes JG. The NICU Antibiotics and Outcomes (NANO) trial: a randomized multicenter clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants. Trials 2022; 23:428. [PMID: 35606829 PMCID: PMC9125935 DOI: 10.1186/s13063-022-06352-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 04/25/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Early-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2-3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants. METHODS The NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants' index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity. DISCUSSION The NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery. TRIAL REGISTRATION Trial registration data: June 25, 2019 NCT03997266 .
Collapse
Affiliation(s)
- Michael J. Morowitz
- Division of Pediatric General and Thoracic Surgery, University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh of UPMC, Rangos Research Center 6th Floor, 4401 Penn Avenue, Pittsburgh, PA 15224 USA
| | - Anup C. Katheria
- Division of Pediatrics, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA 92123 USA
| | - Richard A. Polin
- Department of Pediatrics, Columbia University, New York, NY 10032 USA
| | - Elizabeth Pace
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, USA
| | - David T. Huang
- Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, USA
| | - Chung-Chou H. Chang
- Department of General Internal Medicine, University of Pittsburgh, Pittsburgh, USA
| | - Johathan G. Yabes
- Department of General Internal Medicine, University of Pittsburgh, Pittsburgh, USA
| |
Collapse
|
|
33
|
Li M, Yang L, Mu C, Sun Y, Gu Y, Chen D, Liu T, Cao H. Gut microbial metabolome in inflammatory bowel disease: From association to therapeutic perspectives. Comput Struct Biotechnol J 2022; 20:2402-2414. [PMID: 35664229 PMCID: PMC9125655 DOI: 10.1016/j.csbj.2022.03.038] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 03/26/2022] [Accepted: 03/31/2022] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a set of clinically chronic, relapsing gastrointestinal inflammatory disease and lacks of an absolute cure. Although the precise etiology is unknown, developments in high-throughput microbial genomic sequencing significantly illuminate the changes in the intestinal microbial structure and functions in patients with IBD. The application of microbial metabolomics suggests that the microbiota can influence IBD pathogenesis by producing metabolites, which are implicated as crucial mediators of host-microbial crosstalk. This review aims to elaborate the current knowledge of perturbations of the microbiome-metabolome interface in IBD with description of altered composition and metabolite profiles of gut microbiota. We emphasized and elaborated recent findings of several potentially protective metabolite classes in IBD, including fatty acids, amino acids and derivatives and bile acids. This article will facilitate a deeper understanding of the new therapeutic approach for IBD by applying metabolome-based adjunctive treatment.
Collapse
Key Words
- AMPs, Antimicrobial peptides
- BAs, Bile acids
- BC, Bray Curtis
- CD, Crohn’s disease
- CDI, Clostridioides difficile infection
- DC, Diversion colitis
- DCA, Deoxycholic acid
- DSS, Dextran sulfate sodium
- FAs, Fatty acid
- FMT, Fecal microbiota transplantation
- FODMAP, Fermentable oligosaccharide, disaccharide, monosaccharide, and polyol
- GC–MS, Gas chromatography-mass spectrometry
- Gut microbiota
- HDAC, Histone deacetylase
- IBD, Inflammatory bowel disease
- Inflammatory bowel diseases
- LC-MS, Liquid chromatography-mass spectrometry
- LCA, Lithocholic acid
- LCFAs, Long-chain fatty acids
- MCFAs, Medium-chain fatty acids
- MD, Mediterranean diet
- MS, Mass spectrometry
- Metabolite
- Metabolomics
- Metagenomics
- Microbial therapeutics
- NMR, Nuclear magnetic resonance
- PBAs, Primary bile acids
- SBAs, Secondary bile acids
- SCD, Special carbohydrate diet
- SCFAs, Short-chain fatty acids
- TNBS, 2,4,6-trinitro-benzene sulfonic acid
- UC, Ulcerative colitis
- UDCA, Ursodeoxycholic acid
- UPLC-MS, ultraperformance liquid chromatography coupled to mass spectrometry
- UU, Unweighted UniFrac
- WMS, Whole-metagenome shotgun
Collapse
Affiliation(s)
| | | | | | - Yue Sun
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yu Gu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Danfeng Chen
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Tianyu Liu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| |
Collapse
|
|
34
|
Zhang P, Lu G, Sun Y, Yan Z, Dang T, Liu J. Metagenomic analysis explores the interaction of aged microplastics and roxithromycin on gut microbiota and antibiotic resistance genes of Carassius auratus. JOURNAL OF HAZARDOUS MATERIALS 2022; 425:127773. [PMID: 34802820 DOI: 10.1016/j.jhazmat.2021.127773] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 11/02/2021] [Accepted: 11/10/2021] [Indexed: 06/13/2023]
Abstract
The aging process changes the physicochemical structure of microplastics and affects environmental behaviors and toxicological effects of coexisting pollutants, thereby posing ecological risks. In this study, the effects of aged polystyrene microplastics alone or in combination with the 100 μg/L roxithromycin (ROX) on intestines of Carassius auratus were investigated. The carrier effect of microplastics was enhanced by aging due to changes in functional groups and surface area, which led to an increase in the bioaccumulation of ROX. The combined exposure of aged microplastics (APS) and ROX caused more inflammatory cell infiltration and cilia defects, and significantly inhibited the activity of amylase and lipase. Metagenomic sequencing revealed that the combined exposure of microplastics and ROX increased the abundance of Gemmobacter, Bosea, Rhizobium, and Shinella and decreased the abundance of Cetobacterium and Akkermansia (p < 0.05). The presence of APS enhanced the selective enrichment of antibiotic resistance genes. What's more, the influence of microplastics and antibiotics on gut microbiota was closely related to carbohydrate metabolism and amino acid metabolism activities, as well as the abundance of baca and sul1 resistance genes. These results expand our understanding of the interaction mechanism between APS and antibiotics in real aquatic environment.
Collapse
Affiliation(s)
- Peng Zhang
- Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China
| | - Guanghua Lu
- Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China.
| | - Yu Sun
- Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China
| | - Zhenhua Yan
- Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China
| | - Tianjian Dang
- Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China
| | - Jianchao Liu
- Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China
| |
Collapse
|
|
35
|
Bai X, Liu G, Yang J, Zhu J, Li X. Gut Microbiota as the Potential Mechanism to Mediate Drug Metabolism Under High-Altitude Hypoxia. Curr Drug Metab 2022; 23:8-20. [PMID: 35088664 DOI: 10.2174/1389200223666220128141038] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/25/2021] [Accepted: 12/30/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND The characteristics of pharmacokinetics and the activity and expression of drug-metabolizing enzymes and transporters significantly change under a high-altitude hypoxic environment. Gut microbiota is an important factor affecting the metabolism of drugs through direct or indirect effects, changing the bioavailability, biological activity, or toxicity of drugs and further affecting the efficacy and safety of drugs in vivo. A high-altitude hypoxic environment significantly changes the structure and diversity of gut microbiota, which may play a key role in drug metabolism under a high-altitude hypoxic environment. METHODS An investigation was carried out by reviewing published studies to determine the role of gut microbiota in the regulation of drug-metabolizing enzymes and transporters. Data and information on expression change in gut microbiota, drug-metabolizing enzymes and transporters under a high-altitude hypoxic environment were explored and proposed. RESULTS High-altitude hypoxia is an important environmental factor that can adjust the structure of the gut microbiota and change the diversity of intestinal microbes. It was speculated that the gut microbiota could regulate drug-metabolizing enzymes through two potential mechanisms, the first being through direct regulation of the metabolism of drugs in vivo and the second being indirect, i.e., through the regulation of drug-metabolizing enzymes and transporters, thereby affecting the activity of drugs. CONCLUSION This article reviews the effects of high-altitude hypoxia on the gut microbiota and the effects of these changes on drug metabolism.
Collapse
Affiliation(s)
- Xue Bai
- Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China
| | - Guiqin Liu
- Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China
| | - Jianxin Yang
- Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China
| | - Junbo Zhu
- Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China
| | - Xiangyang Li
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China
| |
Collapse
|
|
36
|
Qiao J, Shang Z, Liu X, Wang K, Wu Z, Wei Q, Li H. Regulatory Effects of Combined Dietary Supplementation With Essential Oils and Organic Acids on Microbial Communities of Cobb Broilers. Front Microbiol 2022; 12:814626. [PMID: 35046927 PMCID: PMC8761947 DOI: 10.3389/fmicb.2021.814626] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 12/09/2021] [Indexed: 12/12/2022] Open
Abstract
The emergence and spread of antibiotic resistance genes in pathogenic microorganisms have resulted in many countries restricting the use of antibiotics as growth promoters in animal feed. The combined use of essential oils and organic acids can help maintain intestinal health, improve animal growth performance, and alleviate the negative effects of banned antibiotics for certain economically important animals. Although the modes of action for the combined dietary supplementation of essential oils and organic acids such as thymol-citric acid (EOA1) and thymol-butyric acid (EOA2) remain unclear, it is speculated that their activities are achieved through beneficial modulation of gastrointestinal microbial communities and inhibition of pathogen growth. In this study, 16S rDNA amplicon sequencing was used to analyze the effects of treatment with EOA1 and EOA2 on the jejunal, cecal, and fecal microbial communities of Cobb broilers while also evaluating effects over different broiler ages. The intestinal microbial communities of broilers developed with increasing age, and Lactobacillus gradually came to dominate the intestinal communities of treated broilers. Further, the microbial communities of feces were more complex than those of the jejuna and ceca. We systematically elucidate that the longitudinal changes in the intestinal microbial communities of Cobb broiler chickens at different ages. Meanwhile, we found that the addition of EOA1 or EOA2 to the diet: (1) inhibited the proliferation of Ralstonia pickettii and Alcaligenaceae in the jejuna on day 28, (2) promoted the colonization and growth of beneficial bacteria such as Lactobacillus, Clostridia, and Bacteroidia at various growth stages, and (3) enriched the abundance of certain microbiota functions, including biological pathways related to metabolism (e.g., enzyme families). Taken together, the results of this study demonstrate that EOA1 and EOA2 dietary supplementation can affect various microbial metabolic pathways related to the metabolism and absorption of nutrients via regulation of the intestinal microbial community structures of Cobb broilers.
Collapse
Affiliation(s)
- Jiayun Qiao
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Zhiyuan Shang
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Xuejiao Liu
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin, China
| | - Kewei Wang
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Zhiwei Wu
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin, China
| | - Qing Wei
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin, China
| | - Haihua Li
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin, China
| |
Collapse
|
|
37
|
Gomes MDS, Saraiva A, Valente Júnior DT, de Oliveira LL, Correia AM, Serão NVL, Rocha GC. Effect of amino acid blend as alternative to antibiotics for growing pigs. J Anim Sci 2022; 100:6503529. [PMID: 35021211 PMCID: PMC8903138 DOI: 10.1093/jas/skac008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/09/2022] [Indexed: 01/13/2023] Open
Abstract
This study aimed to evaluate the effect of supplementing arginine (Arg) + glutamine (Gln) replacing antibiotics on performance, immune response, and antioxidant capacity of pigs in the growing phase. One hundred fifty 63-d-old pigs with initial body weight (BW) of 25.0 ± 1.46 kg were distributed in a randomized block design, with three treatments and ten replicates. The three diets were control; antibiotic, control + 100 mg/kg tiamulin and 506 mg/kg oxytetracycline; amino acid, control + 10 g/kg Arg and 2 g/kg Gln. Dietary treatments were fed from 63 to 77 d. Following the treatment period, all pigs were fed the control diet from 77 to 90 d. Data were analyzed using GLIMMIX and UNIVARIATE in SAS 9.4. From 63 to 70 d, pigs fed diets with antibiotics had improved (P < 0.05) average daily feed intake, average daily weight gain (ADG), gain to feed ratio (G:F), and 70-d BW compared to those fed control or amino acid diets. From 70 to 77 d, including antibiotics in the diet increased (P < 0.05) ADG and 77-d BW. From 77 to 90 d, pigs fed control or amino acid diets had greater (P < 0.05) ADG than those fed an antibiotic diet. From 63 to 90 d, although pig performance was not affected (P > 0.05), growth curve of pigs fed the antibiotic diets was different (P < 0.05) from those fed the control and amino acids diets. At 70 d, serum tumor necrosis factor-α and diamine oxidase (DAO) were lower (P < 0.05) in pigs fed the antibiotic diet than the control diet, and pigs fed the amino acid diet had intermediate results. Ferric reducing antioxidant power (FRAP) was lower (P < 0.05) in pigs fed the amino acid diet than the antibiotic diet, and pigs fed the control diet had intermediate results. Serum immunoglobulin A was lower (P < 0.05) in pigs fed the antibiotic diet. At 77 d, DAO and serum immunoglobulin G were lower (P < 0.05) in pigs fed the antibiotic diet. FRAP was lower (P < 0.05) in pigs fed the amino acid and control diets. Serum malondialdehyde was higher (P < 0.05) in pigs fed the amino acid diet than those fed the control diet, and pigs fed the antibiotic diet had intermediate results. At 90 d, antibiotics or amino acids did not affect (P > 0.05) serum parameters. Amino acid blend supplementation at the selected doses in this study did not positively affect growing pigs. Although from 63 to 77 d, antibiotics improved performance, when considering the overall study period, growing pigs did not benefit from a diet containing antibiotics.
Collapse
Affiliation(s)
- Maykelly da S Gomes
- Department of Animal Science, Universidade Federal de Viçosa, Minas Gerais 36570-900, Brazil
| | - Alysson Saraiva
- Department of Animal Science, Universidade Federal de Viçosa, Minas Gerais 36570-900, Brazil
| | - Dante T Valente Júnior
- Department of Animal Science, Universidade Federal de Viçosa, Minas Gerais 36570-900, Brazil
| | - Leandro L de Oliveira
- Department of Biology, Universidade Federal de Viçosa, Minas Gerais 36570-900, Brazil
| | - Amanda M Correia
- Department of Animal Science, Universidade Federal de Viçosa, Minas Gerais 36570-900, Brazil
| | - Nicola V L Serão
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
| | - Gabriel C Rocha
- Department of Animal Science, Universidade Federal de Viçosa, Minas Gerais 36570-900, Brazil,Corresponding author:
| |
Collapse
|
|
38
|
Wang T, Ishikawa T, Sasaki M, Chiba T. Oral and Gut Microbial Dysbiosis and Non-alcoholic Fatty Liver Disease: The Central Role of Porphyromonas gingivalis. Front Med (Lausanne) 2022; 9:822190. [PMID: 35308549 PMCID: PMC8924514 DOI: 10.3389/fmed.2022.822190] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/19/2022] [Indexed: 02/05/2023] Open
Abstract
Gut microbiota play many important roles, such as the regulation of immunity and barrier function in the intestine, and are crucial for maintaining homeostasis in living organisms. The disruption in microbiota is called dysbiosis, which has been associated with various chronic inflammatory conditions, food allergies, colorectal cancer, etc. The gut microbiota is also affected by several other factors such as diet, antibiotics and other medications, or bacterial and viral infections. Moreover, there are some reports on the oral-gut-liver axis indicating that the disruption of oral microbiota affects the intestinal biota. Non-alcoholic fatty liver disease (NAFLD) is one of the systemic diseases caused due to the dysregulation of the oral-gut-liver axis. NAFLD is the most common liver disease reported in the developed countries. It includes liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. Recently, accumulating evidence supports an association between NAFLD and dysbiosis of oral and gut microbiota. Periodontopathic bacteria, especially Porphyromonas gingivalis, have been correlated with the pathogenesis and development of NAFLD based on the clinical and basic research, and immunology. P. gingivalis was detected in the liver, and lipopolysaccharide from this bacteria has been shown to be involved in the progression of NAFLD, thereby indicating a direct role of P. gingivalis in NAFLD. Moreover, P. gingivalis induces dysbiosis of gut microbiota, which promotes the progression of NAFLD, through disrupting both metabolic and immunologic pathways. Here, we review the roles of microbial dysbiosis in NAFLD. Focusing on P. gingivalis, we evaluate and summarize the most recent advances in our understanding of the relationship between oral-gut microbiome symbiosis and the pathogenesis and progression of non-alcoholic fatty liver disease, as well as discuss novel strategies targeting both P. gingivalis and microbial dysbiosis.
Collapse
Affiliation(s)
- Ting Wang
- Division of Internal Medicine, Department of Oral Medicine, Iwate Medical University, Morioka, Japan
- Ting Wang
| | - Taichi Ishikawa
- Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, Morioka, Japan
| | - Minoru Sasaki
- Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, Morioka, Japan
| | - Toshimi Chiba
- Division of Internal Medicine, Department of Oral Medicine, Iwate Medical University, Morioka, Japan
- *Correspondence: Toshimi Chiba
| |
Collapse
|
|
39
|
Xiao H, Fan Y, Li Y, Dong J, Zhang S, Wang B, Liu J, Liu X, Fan S, Guan J, Cui M. Oral microbiota transplantation fights against head and neck radiotherapy-induced oral mucositis in mice. Comput Struct Biotechnol J 2021; 19:5898-5910. [PMID: 34815834 PMCID: PMC8579069 DOI: 10.1016/j.csbj.2021.10.028] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 10/13/2021] [Accepted: 10/21/2021] [Indexed: 02/08/2023] Open
Abstract
Oral mucositis is a common radiotherapy-induced complication among nasal, oral and laryngeal cancer (NOALC) patients. This complication leads to decreased quality of life and has few treatments. Here, fractionated radiation was performed to mimic radiotherapy for NOALCs in mouse models. Oral microbiota transplantation (OMT) mitigated oral mucositis, as judged by reconstructed epithelium and tongue papillae, fewer infiltrated leukocytes and more proliferative cells in the oral epithelium. The gut microbiota impacted oral mucositis progression, and OMT restructured oral and gut bacteria configurations and reprogrammed the gene expression profile of tongue tissues. In vivo silencing of glossal S100 calcium binding protein A9 debilitated the radioprotection of OMT. In light of clinical samples, we identified that patients with different alteration trends of Lactobacillaceae frequency presented different primary lesions and prognoses of NOALC following radiotherapy. Together, our findings provide new insights into the oral-gut microbiota axis and underpin the suggestion that OMT might be harnessed as a novel remedy to fight against oral mucositis in NOALC patients following radiotherapy in preclinical settings. Of note, oral microorganisms, such as Lactobacillaceae, might be employed as biomarkers to predict the prognosis of NOALC with radiotherapy.
Collapse
Affiliation(s)
- Huiwen Xiao
- Department of Microbiology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.,Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin 300192, China
| | - Yao Fan
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yuan Li
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin 300192, China
| | - Jiali Dong
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin 300192, China
| | - Shuqin Zhang
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin 300192, China
| | - Bin Wang
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin 300192, China
| | - Jia Liu
- Department of Microbiology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China
| | - Xingzhong Liu
- Department of Microbiology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China
| | - Saijun Fan
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin 300192, China
| | - Jian Guan
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Ming Cui
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin 300192, China
| |
Collapse
|
|
40
|
Microbiomes in the Intestine of Developing Pigs: Implications for Nutrition and Health. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1354:161-176. [PMID: 34807442 DOI: 10.1007/978-3-030-85686-1_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The past decade has seen an expansion of studies on the role of gut microbiome in piglet nutrition and health. With the help of culture-independent sequencing techniques, the colonization of gut microbiota and their implication in physiology are being investigated in depth. Immediately after birth, the microbes begin to colonize following an age-dependent trajectory, which can be modified by maternal environment, diet, antibiotics, and fecal microbiota transplantation. The early-life gut microbiome is relatively simple but enriched with huge metabolic potential to utilize milk oligosaccharides and affect the epithelial function. After weaning, the gut microbiome develops towards a gradual adaptation to the introduction of solid food, with an enhanced ability to metabolize amino acids, fibers, and bile acids. Here we summarize the compositional and functional difference of the gut microbiome in the keystone developing phases, with a specific focus on the use of different nutritional approaches based on the phase-specific gut microbiome.
Collapse
|
|
41
|
Su Y, Gan XP, Li FF, Zhang DY, Chen L, Cao YN, Qiu HH, Cheng DC, Zu JF, Liu WY, Wang HK, Xu XM. Effect of exposure to antibiotics on the gut microbiome and biochemical indexes of pregnant women. BMJ Open Diabetes Res Care 2021; 9:9/2/e002321. [PMID: 34732397 PMCID: PMC8572386 DOI: 10.1136/bmjdrc-2021-002321] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 10/05/2021] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION Exposure to antibiotics (ABX) during pregnancy can have a systematic effect on both fetal and maternal health. Although previous biomonitoring studies have indicated the effects on children of extensive exposure to ABX, studies on pregnant women remain scarce. To explore the effect on pregnant women of environmental exposure to ABX through accidental ingestion and identify potential health risks, the present study investigated 122 pregnant women in East China between 2019 and 2020. RESEARCH DESIGN AND METHODS The presence of six categories of ABX (quinolones, sulfonamides, lincosamides, tetracyclines, amide alcohol ABX, and β-lactams) in plasma samples taken from the pregnant women was investigated using an ABX kit and a time-resolved fluorescence immunoassay. RESULTS All six ABX were detected in the plasma, with a detection rate of 17.2%. It was discovered that the composition of intestinal flora in pregnant women exposed to ABX was different from that of pregnant women who had not been exposed to ABX. The intestinal flora of pregnant women exposed to ABX also changed at both the phylum and genus levels, and several genera almost disappeared. Furthermore, the metabolic levels of glucose and insulin and the alpha diversity of pregnant women exposed to ABX were higher than those of pregnant women not exposed to ABX. CONCLUSION Pregnant women are potentially at higher risk of adverse microbial effects. Glucose metabolism and insulin levels were generally higher in pregnant women exposed to ABX than in unexposed women. Also, the composition and color of the gut microbiome changed.
Collapse
Affiliation(s)
- Yao Su
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
- Shanghai Jiao Tong University School of Medicine, Shanghai, Huangpu District, China
| | - Xu-Pei Gan
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
| | - Fei-Fei Li
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
| | - Dong-Yao Zhang
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
- Shanghai Jiao Tong University School of Medicine, Shanghai, Huangpu District, China
| | - Li Chen
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
- Shanghai Jiao Tong University School of Medicine, Shanghai, Huangpu District, China
| | - Yan-Nan Cao
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
| | - Hong-Hui Qiu
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
- Shanghai Jiao Tong University School of Medicine, Shanghai, Huangpu District, China
| | - De-Cui Cheng
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
| | - Jian-Fei Zu
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
| | - Wen-Yu Liu
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
- Shanghai Jiao Tong University School of Medicine, Shanghai, Huangpu District, China
| | - Hong-Kun Wang
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
| | - Xian-Ming Xu
- Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, Hongkou District, China
| |
Collapse
|
|
42
|
Polak K, Jobbágy A, Muszyński T, Wojciechowska K, Frątczak A, Bánvölgyi A, Bergler-Czop B, Kiss N. Microbiome Modulation as a Therapeutic Approach in Chronic Skin Diseases. Biomedicines 2021; 9:biomedicines9101436. [PMID: 34680552 PMCID: PMC8533290 DOI: 10.3390/biomedicines9101436] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/30/2021] [Accepted: 10/06/2021] [Indexed: 02/07/2023] Open
Abstract
There is a growing quantity of evidence on how skin and gut microbiome composition impacts the course of various dermatological diseases. The strategies involving the modulation of bacterial composition are increasingly in the focus of research attention. The aim of the present review was to analyze the literature available in PubMed (MEDLINE) and EMBASE databases on the topic of microbiome modulation in skin diseases. The effects and possible mechanisms of action of probiotics, prebiotics and synbiotics in dermatological conditions including atopic dermatitis (AD), psoriasis, chronic ulcers, seborrheic dermatitis, burns and acne were analyzed. Due to the very limited number of studies available regarding the topic of microbiome modulation in all skin diseases except for AD, the authors decided to also include case reports and original studies concerning oral administration and topical application of the pro-, pre- and synbiotics in the final analysis. The evaluated studies mostly reported significant health benefits to the patients or show promising results in animal or ex vivo studies. However, due to a limited amount of research and unambiguous results, the topic of microbiome modulation as a therapeutic approach in skin diseases still warrants further investigation.
Collapse
Affiliation(s)
- Karina Polak
- Doctoral School, Medical University of Silesia, 40-055 Katowice, Poland; (K.P.); (K.W.)
| | - Antal Jobbágy
- Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, H-1085 Budapest, Hungary; (A.J.); (A.B.)
| | - Tomasz Muszyński
- Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 31-530 Cracow, Poland;
| | - Kamila Wojciechowska
- Doctoral School, Medical University of Silesia, 40-055 Katowice, Poland; (K.P.); (K.W.)
| | - Aleksandra Frątczak
- Chair and Department of Dermatology, Medical University of Silesia, 40-027 Katowice, Poland; (A.F.); (B.B.-C.)
| | - András Bánvölgyi
- Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, H-1085 Budapest, Hungary; (A.J.); (A.B.)
| | - Beata Bergler-Czop
- Chair and Department of Dermatology, Medical University of Silesia, 40-027 Katowice, Poland; (A.F.); (B.B.-C.)
| | - Norbert Kiss
- Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, H-1085 Budapest, Hungary; (A.J.); (A.B.)
- Correspondence:
| |
Collapse
|
|
43
|
Velikova T, Snegarova V, Kukov A, Batselova H, Mihova A, Nakov R. Gastrointestinal mucosal immunity and COVID-19. World J Gastroenterol 2021; 27:5047-5059. [PMID: 34497434 PMCID: PMC8384742 DOI: 10.3748/wjg.v27.i30.5047] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 05/01/2021] [Accepted: 07/12/2021] [Indexed: 02/06/2023] Open
Abstract
As the gastrointestinal tract may also be a crucial entry or interaction site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the role of the gut mucosal immune system as a first-line physical and immunological defense is critical. Furthermore, gastrointestinal involvement and symptoms in coronavirus disease 2019 (COVID-19) patients have been linked to worse clinical outcomes. This review discusses recent data on the interactions between the virus and the immune cells and molecules in the mucosa during the infection. By carrying out appropriate investigations, the mucosal immune system role in SARS-CoV-2 infection in therapy and prevention can be established. In line with this, COVID-19 vaccines that stimulate mucosal immunity against the virus may have more advantages than the others.
Collapse
Affiliation(s)
- Tsvetelina Velikova
- Department of Clinical Immunology, University Hospital Lozenetz, Medical Faculty, Sofia University, St. Kliment Ohridski, Sofia 1407, Bulgaria
| | - Violeta Snegarova
- Clinic of Internal Diseases, Naval Hospital – Varna, Military Medical Academy, Medical Faculty, Medical University, Varna 9000, Bulgaria
| | - Alexander Kukov
- Department of Clinical Immunology, University Hospital Lozenetz, Medical Faculty, Sofia University, St. Kliment Ohridski, Sofia 1407, Bulgaria
| | - Hristiana Batselova
- Department of Epidemiology and Disaster Medicine, Medical University, Plovdiv, University Hospital "St George", Plovdiv 6000, Bulgaria
| | - Antoaneta Mihova
- Department of Clinical Immunology, University Hospital Lozenetz, Medical Faculty, Sofia University, St. Kliment Ohridski, Sofia 1407, Bulgaria
| | - Radislav Nakov
- Clinic of Gastroenterology, Tsaritsa Joanna University Hospital, Medical University of Sofia, Sofia 1527, Bulgaria
| |
Collapse
|
|
44
|
Chen LJ, He JT, Pan M, Liu JL, Zhang KK, Li JH, Wang LB, Xu LL, Chen YK, Zhang QY, Li DR, Xu JT, Xie XL. Antibiotics Attenuate Methamphetamine-Induced Hepatotoxicity by Regulating Oxidative Stress and TLR4/MyD88/Traf6 Axis. Front Pharmacol 2021; 12:716703. [PMID: 34381368 PMCID: PMC8350338 DOI: 10.3389/fphar.2021.716703] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 06/28/2021] [Indexed: 12/12/2022] Open
Abstract
Methamphetamine (METH) is a major psychostimulant drug of abuse worldwide, and its neurotoxicity has been studied extensively. In addition to neurotoxicity, METH can also induce hepatotoxicity. The underlying mechanism of intestinal microorganisms in METH-induced hepatotoxicity remains unclear. In this study, mice have received antibiotics intragastrically or PBS once each day for 1 week, followed by METH or saline. The antibiotics attenuated METH-induced hepatotoxicity as evidenced by histopathological observation and biochemical analysis; furthermore, they alleviated METH-induced oxidative stress. The effect of antibiotics on METH-induced hepatotoxicity was investigated using RNA-sequencing (RNA-seq). The RNA-seq results demonstrated that antibiotics could regulate 580 differentially expressed genes (DEGs), of which 319 were upregulated after METH treatment and then downregulated with antibiotic pretreatment and 237 were first downregulated after METH administration and then upregulated after antibiotic pretreatment, in addition to 11 upregulated and 13 downregulated ones simultaneously in METH and antibiotic-pretreated groups. RNA-seq analyses revealed that TLR4 is one of the hub genes. Western blot analysis indicated that antibiotics inhibited the increase of TLR4, MyD88 and Traf6 induced by METH. This research suggests that antibiotics may play an important role in preventing METH-induced liver injury by regulating oxidative stress and TLR4/MyD88/Traf6 axis, though further investigation is required.
Collapse
Affiliation(s)
- Li-Jian Chen
- Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, Guangzhou, China
| | - Jie-Tao He
- Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, Guangzhou, China.,Department of Basic Medicine and Biomedical Engineering, School of Medicine, Foshan University, Foshan, China
| | - Ming Pan
- Department of Anesthesiology, Dalian Municipal Central Hospital, Dalian, China
| | - Jia-Li Liu
- Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, Guangzhou, China
| | - Kai-Kai Zhang
- Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, Guangzhou, China
| | - Jia-Hao Li
- Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, Guangzhou, China
| | - Li-Bin Wang
- Department of Toxicology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, China
| | - Ling-Ling Xu
- Department of Toxicology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, China
| | - Yu-Kui Chen
- Department of Toxicology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, China
| | - Qin-Yao Zhang
- Department of Toxicology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, China
| | - Dong-Ri Li
- Department of Forensic Evidence Science, School of Forensic Medicine, Southern Medical University, Guangzhou, China
| | - Jing-Tao Xu
- Department of Forensic Clinical Medicine, School of Forensic Medicine, Southern Medical University, Guangzhou, China
| | - Xiao-Li Xie
- Department of Toxicology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, China
| |
Collapse
|
|
45
|
Beydoun S, Fardous AM, Saruna MM, Beydoun AG, Sorge JA, Ma H, Aoun G, Unnikrishnan A, Cabelof DC, Heydari AR. Succinylsulfathiazole modulates the mTOR signaling pathway in the liver of c57BL/6 mice via a folate independent mechanism. Exp Gerontol 2021; 150:111387. [PMID: 33957263 PMCID: PMC8165018 DOI: 10.1016/j.exger.2021.111387] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/25/2021] [Accepted: 04/28/2021] [Indexed: 01/27/2023]
Abstract
Researchers studying the effect of folate restriction on rodents have resorted to the use of the antibiotic succinylsulfathiazole (SST) in the folate depleted diet to induce a folate deficient status. SST has been used extensively in rodent studies since the 1940s. Its localized effect on the gut bacteria as well as its effectiveness in reducing folate producing species is well documented. The possible overlap between the pathways affected by folate depletion and SST could potentially produce a confounding variable in such studies. In our novel study, we analyzed the effect of SST on folate levels in c57Bl/6 male mice fed folate supplemented and deficient diets. We did not observe any significant difference on growth and weight gain at 21 weeks. SST did not significantly affect folate levels in the plasma, liver and colon tissues; however, it did alter energy metabolism and expression of key genes in the mTOR signaling pathway in the liver. This research sheds light on a possible confounding element when using SST to study folate depletion due to the potential overlap with multiple critical pathways such as mTOR. SUMMARY: The antibiotic succinylsulfathiazole (SST) is used to reduce folate producing bacteria in rodent folate depletion studies. SST can modulate critical energy and nutrient sensing pathways converging onto mTOR signaling, and potentially confounding cancer studies.
Collapse
Affiliation(s)
- Safa Beydoun
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Ali M Fardous
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA
| | - Michael M Saruna
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA
| | - Ali G Beydoun
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA
| | - Johnathan A Sorge
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA
| | - Hongzhi Ma
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA
| | - Ghada Aoun
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA
| | - Archana Unnikrishnan
- Department of Biochemistry and Molecular Biology, University of Oklahoma Health and Science Center, OK 73104, USA
| | - Diane C Cabelof
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA; Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48202, USA
| | - Ahmad R Heydari
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA; Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48202, USA.
| |
Collapse
|
|
46
|
Huang X, Chen L, Li Z, Zheng B, Liu N, Fang Q, Jiang J, Rao T, Ouyang D. The efficacy and toxicity of antineoplastic antimetabolites: Role of gut microbiota. Toxicology 2021; 460:152858. [PMID: 34273448 DOI: 10.1016/j.tox.2021.152858] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 07/01/2021] [Accepted: 07/12/2021] [Indexed: 02/06/2023]
Abstract
The incidence and mortality of cancer are rapidly growing all over the world. Nowadays, antineoplastic antimetabolites still play a key role in the chemotherapy of cancer. However, the interindividual variations in the efficacy and toxicity of antineoplastic antimetabolites are nonnegligible challenges to their clinical applications. Although many studies have focused on genetic variation, the reasons for these interindividual variations have still not been fully understood. Gut microbiota is reported to be associated with the efficacy and toxicity of antineoplastic antimetabolites. In this review, we summarize the interaction of antineoplastic antimetabolites on gut microbiota and the influences of shifted gut microbiota profiles on the efficacy and toxicity of antineoplastic antimetabolites. The factors affecting the efficacy and toxicity of antineoplastic antimetabolites via gut microbiota are also discussed. In addition, we present our viewpoints that regulating the gut microbiota may increase the efficacy and decrease the toxicity of antineoplastic antimetabolites. This will help us better understand the new mechanism via gut microbiota and promote individualized use of antineoplastic antimetabolites.
Collapse
Affiliation(s)
- Xinyi Huang
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
| | - Lulu Chen
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, 411000, PR China
| | - Zhenyu Li
- National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, Hunan, PR China; Department of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China
| | - Binjie Zheng
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
| | - Na Liu
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
| | - Qing Fang
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
| | - Jinsheng Jiang
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China; Sanjin Group Hunan Sanjin Pharmaceutical Co., Ltd., 320 Deshan Road, Hunan, 415000, PR China
| | - Tai Rao
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China.
| | - Dongsheng Ouyang
- Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China.
| |
Collapse
|
|
47
|
Hagi T, Belzer C. The interaction of Akkermansia muciniphila with host-derived substances, bacteria and diets. Appl Microbiol Biotechnol 2021; 105:4833-4841. [PMID: 34125276 PMCID: PMC8236039 DOI: 10.1007/s00253-021-11362-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 05/11/2021] [Accepted: 05/20/2021] [Indexed: 12/17/2022]
Abstract
Abstract Trillions of microbes inhabit the human gut and build extremely complex communities. Gut microbes contribute to host metabolisms for better or worse and are widely studied and associated with health and disease. Akkermansia muciniphila is a gut microbiota member, which uses mucin as both carbon and nitrogen sources. Many studies on A. muciniphila have been conducted since this unique bacterium was first described in 2004. A. muciniphila can play an important role in our health because of its beneficial effects, such as improving type II diabetes and obesity and anti-inflammation. A. muciniphila establishes its position as a next-generation probiotic. Besides the effect of A. muciniphila on host health, a technique for boosting has been investigated. In this review, we show what factors can modulate the abundance of A. muciniphila focusing on the interaction with host-derived substances, other bacteria and diets. This review also refers to the possibility of the interaction between medicine and A. muciniphila; this will open up future treatment strategies that can increase A. muciniphila abundance in the gut. Key points • Host-derived substances such as bile, microRNA and melatonin as well as mucin have beneficial effects on A. muciniphila. • Gut and probiotic bacteria and diet ingredients such as carbohydrates and phytochemicals could boost the abundance of A. muciniphila. • Several medicines could affect the growth of A. muciniphila.
Collapse
Affiliation(s)
- Tatsuro Hagi
- Institute of Livestock and Grassland Science, National Agriculture and Food Research Organisation (NARO), 2 Ikenodai, Tsukuba, Ibaraki, 305-0901, Japan.
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University and Research, 6708 WE, Wageningen, The Netherlands.
| |
Collapse
|
|
48
|
Banfi D, Moro E, Bosi A, Bistoletti M, Cerantola S, Crema F, Maggi F, Giron MC, Giaroni C, Baj A. Impact of Microbial Metabolites on Microbiota-Gut-Brain Axis in Inflammatory Bowel Disease. Int J Mol Sci 2021; 22:1623. [PMID: 33562721 PMCID: PMC7915037 DOI: 10.3390/ijms22041623] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/29/2021] [Accepted: 02/02/2021] [Indexed: 02/07/2023] Open
Abstract
The complex bidirectional communication system existing between the gastrointestinal tract and the brain initially termed the "gut-brain axis" and renamed the "microbiota-gut-brain axis", considering the pivotal role of gut microbiota in sustaining local and systemic homeostasis, has a fundamental role in the pathogenesis of Inflammatory Bowel Disease (IBD). The integration of signals deriving from the host neuronal, immune, and endocrine systems with signals deriving from the microbiota may influence the development of the local inflammatory injury and impacts also more distal brain regions, underlying the psychophysiological vulnerability of IBD patients. Mood disorders and increased response to stress are frequently associated with IBD and may affect the disease recurrence and severity, thus requiring an appropriate therapeutic approach in addition to conventional anti-inflammatory treatments. This review highlights the more recent evidence suggesting that alterations of the microbiota-gut-brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as "postbiotics", such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. The last section covers a critical evaluation of the main clinical evidence pointing to the microbiome-based therapeutic approaches for the treatment of IBD-related gastrointestinal and neuropsychiatric symptoms.
Collapse
Affiliation(s)
- Davide Banfi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Elisabetta Moro
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy; (E.M.); (F.C.)
| | - Annalisa Bosi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Michela Bistoletti
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Silvia Cerantola
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy; (S.C.); (M.C.G.)
| | - Francesca Crema
- Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy; (E.M.); (F.C.)
| | - Fabrizio Maggi
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| | - Maria Cecilia Giron
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy; (S.C.); (M.C.G.)
| | - Cristina Giaroni
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
- Centre of Neuroscience, University of Insubria, 21100 Varese, Italy
| | - Andreina Baj
- Department of Medicine and Surgery, University of Insubria, via H Dunant 5, 21100 Varese, Italy; (D.B.); (A.B.); (M.B.); (F.M.); (A.B.)
| |
Collapse
|
|
49
|
Escudero-Sánchez R, Ponce-Alonso M, Barragán-Prada H, Morosini MI, Cantón R, Cobo J, del Campo R. Long-Term Impact of Suppressive Antibiotic Therapy on Intestinal Microbiota. Genes (Basel) 2020; 12:genes12010041. [PMID: 33396759 PMCID: PMC7823557 DOI: 10.3390/genes12010041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/20/2020] [Accepted: 12/29/2020] [Indexed: 02/07/2023] Open
Abstract
The aim was to describe the safety of indefinite administration of antibiotics, the so-called suppressive antibiotic therapy (SAT) and to provide insight into their impact on gut microbiota. 17 patients with SAT were recruited, providing a fecal sample. Bacterial composition was determined by 16S rDNA massive sequencing, and their viability was explored by PCR-DGGE with and without propidium monoazide. Presence of antibiotic multirresistant bacteria was explored through the culture of feces in selective media. High intra-individual variability in the genera distribution regardless of the antibiotic or antibiotic administration ingestion period, with few statistically significant differences detected by Bray-Curtis distance-based principle component analysis, permutational multivariate analysis of variance and linear discriminant analysis effect size analysis. However, the microbiota composition of patients treated with both beta-lactams and sulfonamides clustered by a heat map. Curiously, the detection of antibiotic resistant bacteria was almost anecdotic and CTX-M-15-producing E. coli were detected in two subjects. Our work demonstrates the overall clinical safety of SAT and the low rate of the selection of multidrug-resistant bacteria triggered by this therapy. We also describe the composition of intestinal microbiota under the indefinite use of antibiotics for the first time.
Collapse
Affiliation(s)
- Rosa Escudero-Sánchez
- Servicio de Enfermedades Infecciosas, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and Red Española de Investigación en Patología Infecciosa (REIPI), 28034 Madrid, Spain; (R.E.-S.); (J.C.)
| | - Manuel Ponce-Alonso
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and Red Española de Investigación en Patología Infecciosa (REIPI), 28034 Madrid, Spain; (M.P.-A.); (M.I.M.); (R.C.)
| | - Hugo Barragán-Prada
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain;
| | - María Isabel Morosini
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and Red Española de Investigación en Patología Infecciosa (REIPI), 28034 Madrid, Spain; (M.P.-A.); (M.I.M.); (R.C.)
| | - Rafael Cantón
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and Red Española de Investigación en Patología Infecciosa (REIPI), 28034 Madrid, Spain; (M.P.-A.); (M.I.M.); (R.C.)
| | - Javier Cobo
- Servicio de Enfermedades Infecciosas, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and Red Española de Investigación en Patología Infecciosa (REIPI), 28034 Madrid, Spain; (R.E.-S.); (J.C.)
| | - Rosa del Campo
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), and Red Española de Investigación en Patología Infecciosa (REIPI), 28034 Madrid, Spain; (M.P.-A.); (M.I.M.); (R.C.)
- Correspondence: ; Tel.: +34-913-368-832
| |
Collapse
|
|
50
|
Rosignoli C, Petruzzellis G, Radici V, Facchin G, Girgenti M, Stella R, Isola M, Battista M, Sperotto A, Geromin A, Cerno M, Arzese A, Deias P, Tascini C, Fanin R, Patriarca F. Risk Factors and Outcome of C. difficile Infection after Hematopoietic Stem Cell Transplantation. J Clin Med 2020; 9:jcm9113673. [PMID: 33207616 PMCID: PMC7696044 DOI: 10.3390/jcm9113673] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 11/07/2020] [Accepted: 11/11/2020] [Indexed: 12/14/2022] Open
Abstract
Patients who undergo hematopoietic stem cell transplants (HSCT) are at major risk of C. difficile (CD) infection (CDI), the most common cause of nosocomial diarrhea. We conducted a retrospective study, which enrolled 481 patients who underwent autologous (220) or allogeneic HSCT (261) in a 5-year period, with the aim of identifying the incidence, risk factors and outcome of CDI between the start of conditioning and 100 days after HSCT. The overall cumulative incidence of CDI based upon clinical evidence was 5.4% (95% CI, 3.7% to 7.8%), without any significant difference between the two types of procedures. The median time between HSCT and CDI diagnosis was 12 days. Out of 26 patients, 19 (73%) with clinical and symptomatic evidence of CDI were positive also for enzymatic or molecular detection of toxigenic CD; in particular, in 5 out of 26 patients (19%) CD binary toxin was also detected. CDI diagnoses significantly increased in the period 2018-2019, since the introduction in the microbiology lab unit of the two-step diagnostic test based on GDH immunoenzymatic detection and toxin B/binary toxin/027 ribotype detection by real-time PCR. Via multivariate analysis, abdominal surgery within 10 years before HSCT (p = 0.002), antibiotic therapy within two months before HSCT (p = 0.000), HCV infection (p = 0.023) and occurrence of bacterial or fungal infections up to 100 days after HSCT (p = 0.003) were significantly associated with a higher risk of CDI development. The 26 patients were treated with first-line vancomycin (24) or fidaxomicine (2) and only 2 patients needed a second-line treatment, due to the persistence of stool positivity. No significant relationship was identified between CDI and the development of acute graft versus host disease (GVHD) after allogeneic HSCT. At a median follow-up of 25 months (range 1-65), the cumulative incidence of transplant related mortality (TRM) was 16.6% (95% CI 11.7% to 22.4%) and the 3-year overall survival (OS) was 67.0% (95% CI 61.9% to 71.6%). The development of CDI had no significant impact on TRM and OS, which were significantly impaired in the multivariate analysis by gastrointestinal and urogenital comorbidities, severe GVHD, previous infections or hospitalization within two months before HSCT, active disease at transplant and occurrence of infections after HSCT. We conclude that 20% of all episodes of diarrhea occurring up to 100 days after HSCT were related to toxigenic CD infection. Patients with a history of previous abdominal surgery or HCV infection, or those who had received broad spectrum parenteral antibacterial therapy were at major risk for CDI development. CDIs were successfully treated with vancomycin or fidaxomicin after auto-HSCT as well as after allo-HSCT.
Collapse
Affiliation(s)
- Chiara Rosignoli
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Giuseppe Petruzzellis
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Vera Radici
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Gabriele Facchin
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Marco Girgenti
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Rossella Stella
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Miriam Isola
- Istituto di Statistica, Dipartimento di Area Medica, Università di Udine, 33100 Udine, Italy;
| | - Martalisa Battista
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Alessandra Sperotto
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Antonella Geromin
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Michela Cerno
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Alessandra Arzese
- SOC Microbiologia, Azienda Sanitaria Friuli Centrale, 33100 Udine, Italy;
- Dipartimento di Area Medica, Università di Udine, 33100 Udine, Italy
| | - Paola Deias
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
| | - Carlo Tascini
- SOC Malattie Infettive, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy;
| | - Renato Fanin
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
- SOC Malattie Infettive, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy;
| | - Francesca Patriarca
- Clinica Ematologica ed Unità di Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Piazzale S. Maria della Misericordia 10, 33100 Udine, Italy; (C.R.); (G.P.); (V.R.); (G.F.); (M.G.); (R.S.); (M.B.); (A.S.); (A.G.); (M.C.); (P.D.); (R.F.)
- SOC Malattie Infettive, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy;
- Correspondence:
| |
Collapse
|