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Fumagalli A, Castells-Nobau A, Trivedi D, Garre-Olmo J, Puig J, Ramos R, Ramió-Torrentà L, Pérez-Brocal V, Moya A, Swann J, Martin-Garcia E, Maldonado R, Fernández-Real JM, Mayneris-Perxachs J. Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism. Gut Microbes 2025; 17:2455506. [PMID: 39910065 PMCID: PMC11810085 DOI: 10.1080/19490976.2025.2455506] [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: 09/30/2024] [Revised: 12/28/2024] [Accepted: 01/13/2025] [Indexed: 02/07/2025] Open
Abstract
The relationship between bacteria, cognitive function and obesity is well established, yet the role of archaeal species remains underexplored. We used shotgun metagenomics and neuropsychological tests to identify microbial species associated with cognition in a discovery cohort (IRONMET, n = 125). Interestingly, methanogen archaeas exhibited the strongest positive associations with cognition, particularly Methanobrevibacter smithii (M. smithii). Stratifying individuals by median-centered log ratios (CLR) of M. smithii (low and high M. smithii groups: LMs and HMs) revealed that HMs exhibited better cognition and distinct gut bacterial profiles (PERMANOVA p = 0.001), characterized by increased levels of Verrucomicrobia, Synergistetes and Lentisphaerae species and reduced levels of Bacteroidetes and Proteobacteria. Several of these species were linked to the cognitive test scores. These findings were replicated in a large-scale validation cohort (Aging Imageomics, n = 942). Functional analyses revealed an enrichment of energy, butyrate, and bile acid metabolism in HMs in both cohorts. Global plasma metabolomics by CIL LC-MS in IRONMET identified an enrichment of methylhistidine, phenylacetate, alpha-linolenic and linoleic acid, and secondary bile acid metabolism associated with increased levels of 3-methylhistidine, phenylacetylgluamine, adrenic acid, and isolithocholic acid in the HMs group. Phenylacetate and linoleic acid metabolism also emerged in the Aging Imageomics cohort performing untargeted HPLC-ESI-MS/MS metabolic profiling, while a targeted bile acid profiling identified again isolithocholic acid as one of the most significant bile acid increased in the HMs. 3-Methylhistidine levels were also associated with intense physical activity in a second validation cohort (IRONMET-CGM, n = 116). Finally, FMT from HMs donors improved cognitive flexibility, reduced weight, and altered SCFAs, histidine-, linoleic acid- and phenylalanine-related metabolites in the dorsal striatum of recipient mice. M. smithii seems to interact with the bacterial ecosystem affecting butyrate, histidine, phenylalanine, and linoleic acid metabolism with a positive impact on cognition, constituting a promising therapeutic target to enhance cognitive performance, especially in subjects with obesity.
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Affiliation(s)
- Andrea Fumagalli
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Girona, Spain
- Integrative Systems Medicine and Biology Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Salt, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III; Madrid, Spain
| | - Anna Castells-Nobau
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Girona, Spain
- Integrative Systems Medicine and Biology Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Salt, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III; Madrid, Spain
| | - Dakshat Trivedi
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Josep Garre-Olmo
- serra-hunter program Department of Nursing, University of Girona, Girona, Spain
| | - Josep Puig
- Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain
- Institute of Diagnostic Imaging (IDI)-Research Unit (IDIR), Parc Sanitari Pere Virgili, Barcelona, Spain
- Medical Imaging, Girona Biomedical Research Institute (IdibGi), Girona, Spain
- Department of Radiology (IDI), Dr. Josep Trueta University Hospital, Girona, Spain
| | - Rafel Ramos
- Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain
- Vascular Health Research Group of Girona (ISV-Girona), Jordi Gol Institute for Primary Care Research (Institut Universitari per a la Recerca en Atenció Primària Jordi Gol I Gorina -IDIAPJGol), Red de Investigación en Cronicidad, Atención Primaria y Promoción de la Salud-RICAPPS- ISCIII Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, Girona, Catalonia, Spain
- Research in Vascular Health Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Dr. Josep Trueta University Hospital, Girona, Spain
| | - Lluís Ramió-Torrentà
- Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain
- Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Dr. Josep Trueta University Hospital, Girona, Spain
- Neurodegeneration and Neuroinflammation Research Group, IDIBGI-CERCA, Girona, Spain
| | - Vicente Pérez-Brocal
- Area of Genomics and Health, Foundation for the Promotion of Sanitary and Biomedical Research of Valencia Region (FISABIO-Public Health), Valencia, Spain
- Biomedical Research Networking Center for Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Andrés Moya
- Area of Genomics and Health, Foundation for the Promotion of Sanitary and Biomedical Research of Valencia Region (FISABIO-Public Health), Valencia, Spain
- Biomedical Research Networking Center for Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Institute for Integrative Systems Biology (I2SysBio), University of Valencia and Spanish National Research Council (CSIC), Valencia, Spain
| | - Jonathan Swann
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Elena Martin-Garcia
- Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
| | - Rafael Maldonado
- Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
| | - José Manuel Fernández-Real
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain
- Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Girona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III; Madrid, Spain
| | - Jordi Mayneris-Perxachs
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain
- Integrative Systems Medicine and Biology Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Salt, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III; Madrid, Spain
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2
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Huang Y, Fang R, Xiong T, Li W, Yu N. The Relationship Between Gut Microbiota and Recurrent Spontaneous Abortion. Microorganisms 2025; 13:1073. [PMID: 40431246 PMCID: PMC12114443 DOI: 10.3390/microorganisms13051073] [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: 03/19/2025] [Revised: 04/20/2025] [Accepted: 05/02/2025] [Indexed: 05/29/2025] Open
Abstract
Recently, the gut microbiota has been found to be associated with multiple organs and systems in the human body, playing a key role in the occurrence and development of various diseases, such as the gut-brain axis and the gut-liver axis. However, its interaction with miscarriages remains poorly understood. This article reviews the characteristics of gut microbiota and its metabolites in patients with recurrent spontaneous abortion (RSA), the mechanism of gut microbiota inducing RSA, and potential therapeutic strategies. Therefore, it provides a new perspective on the gut microbiota in the pathogenesis and treatment of recurrent abortion, and the prospect of the future research direction of gut microbiota and recurrent abortion is proposed based on existing studies.
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Affiliation(s)
- Yiyao Huang
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; (Y.H.); (R.F.)
| | - Ruijie Fang
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; (Y.H.); (R.F.)
| | - Ting Xiong
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; (T.X.); (W.L.)
| | - Wei Li
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; (T.X.); (W.L.)
| | - Nan Yu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; (T.X.); (W.L.)
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Chen Y, Chen Z, Liang L, Li J, Meng L, Yuan W, Xie B, Zhang X, Feng L, Jia Y, Fu Z, Su P, Tong Z, Zhong J, Liu X. Multi-kingdom gut microbiota dysbiosis is associated with the development of pulmonary arterial hypertension. EBioMedicine 2025; 115:105686. [PMID: 40220715 PMCID: PMC12013117 DOI: 10.1016/j.ebiom.2025.105686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 03/07/2025] [Accepted: 03/23/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND Gut microbiota dysbiosis has been implicated in pulmonary arterial hypertension (PAH). However, the exact roles and underlying mechanisms of multi-kingdom gut microbiota, including bacteria, archaea, and fungi, in PAH remain largely unclear. METHODS The shotgun metagenomics was used to analyse multi-kingdom gut microbial communities in patients with idiopathic PAH (IPAH) and healthy controls. Furthermore, fecal microbiota transplantation (FMT) was performed to transfer gut microbiota from IPAH patients or monocrotaline (MCT)-PAH rats to normal rats and from normal rats to MCT-PAH rats. FINDINGS Gut microbiota analysis revealed substantial alterations in the bacterial, archaeal, and fungal communities in patients with IPAH compared with healthy controls. Notably, FMT from IPAH patients or MCT-PAH rats induced PAH phenotypes in recipient rats. More intriguingly, FMT from normal rats to MCT-PAH rats significantly ameliorated PAH symptoms; restored gut bacteria, archaea, and fungi composition; and shifted the plasma metabolite profiles of MCT-PAH rats toward those of normal rats. In parallel, RNA-sequencing analysis demonstrated the expression of genes involved in key signalling pathways related to PAH. A panel of multi-kingdom markers exhibited superior diagnostic accuracy compared with single-kingdom panels for IPAH. INTERPRETATION Our findings established an association between multi-kingdom gut microbiota dysbiosis and PAH, thereby indicating the therapeutic potential of FMT in PAH. More importantly, apart from gut bacteria, gut archaea and fungi were also significantly associated with PAH pathogenesis, highlighting their indispensable role in PAH. FUNDING This work was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Projects No. 2024ZD0531200, No. 2024ZD0531201 (Research on Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases, and Metabolic Diseases), the National Natural Science Foundation of China of China (No. 82170302, 82370432), Financial Budgeting Project of Beijing Institute of Respiratory Medicine (Ysbz2025004, Ysbz2025007), National clinical key speciality construction project Cardiovascular Surgery, Reform and Development Program of Beijing Institute of Respiratory Medicine (Ggyfz202417, Ggyfz202501), Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (CYFH202209).
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Affiliation(s)
- Yihang Chen
- Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China
| | - Zhenzhen Chen
- Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, 100029, China
| | - Lirong Liang
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China; Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 100020, Beijing, China
| | - Jifeng Li
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China
| | - Liukun Meng
- Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing, 100037, China
| | - Wen Yuan
- Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China
| | - Boqia Xie
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China
| | - Xun Zhang
- Department of Pharmacy, Chinese PLA General Hospital, 100039, Beijing, China
| | - Lin Feng
- Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China; Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 100020, Beijing, China
| | - Yanxiong Jia
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China; Department of Cardiac Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China
| | - Zhou Fu
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China; Department of Cardiac Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China
| | - Pixiong Su
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China; Department of Cardiac Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China
| | - Zhaohui Tong
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
| | - Jiuchang Zhong
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
| | - Xiaoyan Liu
- Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
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Jiang R, Kountz DJ, Zhang L, Krzycki JA. A cobalamin-dependent pathway of choline demethylation from the human gut acetogen Eubacterium limosum. J Biol Chem 2025:108524. [PMID: 40280423 DOI: 10.1016/j.jbc.2025.108524] [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: 11/22/2024] [Revised: 03/26/2025] [Accepted: 04/09/2025] [Indexed: 04/29/2025] Open
Abstract
Elevated serum levels of trimethylamine N-oxide (TMAO) are reported to promote the development of atherosclerosis. TMAO is produced by hepatic oxidation of trimethylamine (TMA) produced by the gut microbiome from dietary quaternary amines such as choline. Net TMA production in the gut depends on microbial enzymes that either produce or consume TMA and its precursors. Here we report the elucidation of a novel microbial pathway consuming choline without TMA production. The human gut acetogen Eubacterium limosum grows by demethylating choline to N-N-dimethylaminoethanol. Quantitative mass spectral analysis of the proteome revealed a multi-protein choline to tetrahydrofolate (THF) methyltransferase system present only in choline-grown cells. The components are encoded in a gene cluster on the genome and include MthB, an MttB superfamily member; MthC, homologous to methylotrophic cobalamin-binding proteins; MthA, homologous to cobalamin:THF methyltransferases; and MthK, a protein related to serine kinases. Together, MthB, MthC, and MthA methylate THF with phosphocholine, but not choline or other quaternary amines. MthB specifically methylates Co(I)-MthC with phosphocholine. MthK acts as a bifunctional choline kinase which can utilize ATP or the MthB demethylation product, N,N-dimethylaminoethanol phosphate, to phosphorylate choline. Together, MthK, MthB, MthC, and MthA are proposed to carry out the methylation of THF with choline. These results outline a THF methylation pathway in which choline is first activated with ATP to phosphocholine prior to demethylation to form N,N-dimethylaminoethanol phosphate. The latter can be recycled by MthK to form more phosphocholine without expending additional ATP, thus minimizing energy utilization during choline-dependent acetogenesis.
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Affiliation(s)
| | | | - Liwen Zhang
- Campus Chemical Instrument Center Mass Spectrometry and Proteomics Facility
| | - Joseph A Krzycki
- Department of Microbiology; The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210.
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Kemp JA, Schultz J, Modolon F, Ribeiro-Alves M, Rosado AS, Mafra D. Is there a correlation between TMAO plasma levels and archaea in the gut of patients undergoing hemodialysis? Int Urol Nephrol 2025; 57:1269-1275. [PMID: 39562414 DOI: 10.1007/s11255-024-04273-5] [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: 05/29/2024] [Accepted: 10/28/2024] [Indexed: 11/21/2024]
Abstract
PURPOSE Patients with chronic kidney disease (CKD) present high plasma levels of trimethylamine N-oxide (TMAO), a uremic toxin produced by gut microbiota associated with atherogenesis. Experimental studies have shown that certain methanogenic archaea members use trimethylamine (TMA), the TMAO precursor in the human gut, to produce methane, suggesting a potential strategy to reduce TMAO levels in patients with CKD. Hence, this study aimed to evaluate the association of Archaea in the gut microbiota and TMAO plasma levels in patients with CKD undergoing hemodialysis. METHODS Twenty-five patients were enrolled in the study (15 women, 53 (18) years, BMI, 25.8 (6.75) kg/m2). TMAO plasma levels were evaluated using the HPLC-EM/EM method. Fecal DNA was extracted using a commercial kit. Subsequently, we sequenced the V4 region of the 16S rRNA gene to characterize the microbial composition. NCT04600258 was retrospectively registered in September 2022. RESULTS According to the reference values in the European Uremic Toxins Work Group (EUTox) database, the patients exhibited high TMAO plasma levels, as expected. The most abundant Archaea members were assigned to the Euryarchaeota phylum, the Methanobacteriaceae family, and the genus Methanobrevibacter. A significant negative correlation between TMAO and Methanobrevibacter was observed. CONCLUSIONS To our knowledge, this study represents the first investigation into the correlation between TMAO levels and the prevalence of Archaea in patients with CKD. Our findings support the archaebiotic hypothesis, suggesting that specific members of the archaea community could play a crucial role in reducing TMA production in the human gut, potentially decreasing TMAO synthesis in CKD patients.
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Affiliation(s)
- Julie Ann Kemp
- Post-Graduate Program in Nutrition Sciences, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
| | - Júnia Schultz
- Biological and Environmental Science and Engineering (BESE), Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
| | - Fluvio Modolon
- Oceanographic Institute, University of Sao Paulo, São Paulo, SP, Brazil
| | - Marcelo Ribeiro-Alves
- HIV/AIDS Clinical Research Center, National Institute of Infectology Evandro Chagas (INI/Fiocruz), Rio de Janeiro, RJ, Brazil
| | - Alexandre S Rosado
- Biological and Environmental Science and Engineering (BESE), Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
| | - Denise Mafra
- Post-Graduate Program in Nutrition Sciences, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil
- Graduate Program in Biological Sciences-Physiology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
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Salahi A, Abd El‐Ghany WA. A Spotlight on Archaea in Humans, Livestock and Poultry: A Review. Vet Med Sci 2025; 11:e70263. [PMID: 40028749 PMCID: PMC11875071 DOI: 10.1002/vms3.70263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 12/12/2024] [Accepted: 02/04/2025] [Indexed: 03/05/2025] Open
Abstract
The microbiota includes prokaryotes (archaea and bacteria) and eukaryotes. Archaea are single-celled prokaryotes and essential part of gut microbiome. Researches on archaea in ruminants and humans are more than mono-gastric. The low abundance of archaea in the gut depends on the method used (metagenomics or meta-transcriptomic) and age of people or poultry. The lack of complete recognition of archaea is due to their small number and method of identifying them (16S rRNA gene primers). The uses of archaea include analytical kit, reduce oil pollution, archaeosomes or drugs production, vaccines agents, lipid carriers in the pharmaceutical industry and molybdenum extraction in the nuclear industry. The nutritional functions of methanogenic archaea including feed utilization (ruminants) and efficiency, hydrogen reducing (human), fat deposition and enhancement of energy harvesting in mice, CAZymes genes, cecal fermentation, syntrophic potential, carotenoid source and improved transit time and appetite and SCFAs production. Archaea acting as antibiotics (produce archaeocins, sulfolobicins and halocin KPS1) and as probiotics (archaeobiotics) can reduce TMAU (trimethylaminuria) disease, cardiovascular diseases (CVDs), and atherosclerosis, brain abscess, cancer, colorectal cancer, inflammatory bowel disease (IBD), constipation, obesity, food allergies, asthma and anti-inflammation which can be prevented by using archaea, and other functions include energy homeostasis, heat shock protein (HSP) production and reducing aging.
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Affiliation(s)
- Ahmad Salahi
- Department of Animal ScienceFaculty of AgricultureUniversity of ZanjanZanjanIran
| | - Wafaa A. Abd El‐Ghany
- Department of Poultry DiseasesFaculty of Veterinary MedicineCairo UniversityGizaEgypt
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Li T, Coker OO, Sun Y, Li S, Liu C, Lin Y, Wong SH, Miao Y, Sung JJY, Yu J. Multi-Cohort Analysis Reveals Altered Archaea in Colorectal Cancer Fecal Samples Across Populations. Gastroenterology 2025; 168:525-538.e2. [PMID: 39490771 DOI: 10.1053/j.gastro.2024.10.023] [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: 10/19/2023] [Revised: 09/03/2024] [Accepted: 10/15/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND & AIMS Archaea are important components of the host microbiome, but their roles in colorectal cancer (CRC) remain largely unclear. We aimed to elucidate the contribution of gut archaea to CRC across multiple populations. METHODS This study incorporated fecal metagenomic data from 10 independent cohorts across 7 countries and an additional in-house cohort, totaling 2101 metagenomes (748 CRC, 471 adenoma, and 882 healthy controls [HCs]). Taxonomic profiling was performed using Kraken2 against the Genome Taxonomy Database. Alterations of archaeal communities and their interactions with bacteria, as well as methanogenic functions were analyzed. A Random Forest model was used to identify multicohort diagnostic microbial biomarkers in CRC. RESULTS The overall archaeal alpha diversity shifted from HCs, patients with adenoma, to patients with CRC with the Methanobacteriota phylum enriched while the order Methanomassiliicoccales depleted. At the species level, Methanobrevibacter_A smithii and Methanobrevibacter_A sp002496065 were enriched, whereas 8 species, including Methanosphaera stadtmanae and Methanomassiliicoccus_A intestinalis, were depleted in patients with CRC across multiple cohorts. Among them, M stadtmanae, Methanobrevibacter_A sp900314695, and Methanocorpusculum sp001940805 exhibited a progressive decrease in the HC-adenoma-CRC sequence. CRC-depleted methanogenic archaea exhibited enhanced co-occurring interactions with butyrate-producing bacteria. Consistently, methanogenesis-related genes and pathways were enriched in patients with CRC. A model incorporating archaeal and bacterial biomarkers outperformed single-kingdom models in discriminating patients with CRC from healthy individuals with the area under the curve ranging from 0.744 to 0.931 in leave-one-cohort-out analysis. CONCLUSIONS This multicohort analysis uncovered significant alterations in gut archaea and their interactions with bacteria in healthy individuals, patients with adenoma, and patients with CRC. Archaeal biomarkers, combined with bacterial features, have potential as noninvasive diagnostic biomarkers for CRC.
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Affiliation(s)
- Tianhui Li
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Olabisi Oluwabukola Coker
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Yang Sun
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Disease, Yunan Geriatric Medical Center, Kunming, China
| | - Shiyu Li
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Chuanfa Liu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Yufeng Lin
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Sunny H Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Yinglei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Disease, Yunan Geriatric Medical Center, Kunming, China
| | - Joseph J Y Sung
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Jun Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
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Salas-López M, Vélez-Ixta JM, Rojas-Guerrero DL, Piña-Escobedo A, Hernández-Hernández JM, Rangel-Calvillo MN, Pérez-Cruz C, Corona-Cervantes K, Juárez-Castelán CJ, García-Mena J. Human Milk Archaea Associated with Neonatal Gut Colonization and Its Co-Occurrence with Bacteria. Microorganisms 2025; 13:85. [PMID: 39858853 PMCID: PMC11767358 DOI: 10.3390/microorganisms13010085] [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: 12/13/2024] [Revised: 12/30/2024] [Accepted: 12/31/2024] [Indexed: 01/27/2025] Open
Abstract
Archaea have been identified as early colonizers of the human intestine, appearing from the first days of life. It is hypothesized that the origin of many of these archaea is through vertical transmission during breastfeeding. In this study, we aimed to characterize the archaeal composition in samples of mother-neonate pairs to observe the potential vertical transmission. We performed a cross-sectional study characterizing the archaeal diversity of 40 human colostrum-neonatal stool samples by next-generation sequencing of V5-V6 16S rDNA libraries. Intra- and inter-sample analyses were carried out to describe the Archaeal diversity in each sample type. Human colostrum and neonatal stools presented similar core microbiota, mainly composed of the methanogens Methanoculleus and Methanosarcina. Beta diversity and metabolic prediction results suggest homogeneity between sample types. Further, the co-occurrence network analysis showed associations between Archaea and Bacteria, which might be relevant for these organisms' presence in the human milk and neonatal stool ecosystems. According to relative abundance proportions, beta diversity, and co-occurrence analyses, the similarities found imply that there is vertical transmission of archaea through breastfeeding. Nonetheless, differential abundances between the sample types suggest other relevant sources for colonizing archaea to the neonatal gut.
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Affiliation(s)
- Maricarmen Salas-López
- Departamento de Genética y Biología Molecular, Cinvestav, Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico; (M.S.-L.); (J.M.V.-I.); or (D.L.R.-G.); (A.P.-E.); (J.M.H.-H.)
| | - Juan Manuel Vélez-Ixta
- Departamento de Genética y Biología Molecular, Cinvestav, Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico; (M.S.-L.); (J.M.V.-I.); or (D.L.R.-G.); (A.P.-E.); (J.M.H.-H.)
| | - Diana Laura Rojas-Guerrero
- Departamento de Genética y Biología Molecular, Cinvestav, Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico; (M.S.-L.); (J.M.V.-I.); or (D.L.R.-G.); (A.P.-E.); (J.M.H.-H.)
- Institute of Environmental Sciences, Faculty of Biology, Jagiellonian University, Gronostajowa 7, 31-007 Kraków, Poland
| | - Alberto Piña-Escobedo
- Departamento de Genética y Biología Molecular, Cinvestav, Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico; (M.S.-L.); (J.M.V.-I.); or (D.L.R.-G.); (A.P.-E.); (J.M.H.-H.)
| | - José Manuel Hernández-Hernández
- Departamento de Genética y Biología Molecular, Cinvestav, Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico; (M.S.-L.); (J.M.V.-I.); or (D.L.R.-G.); (A.P.-E.); (J.M.H.-H.)
| | | | - Claudia Pérez-Cruz
- Departamento de Farmacología, Cinvestav, Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico;
| | - Karina Corona-Cervantes
- Departamento de Genética y Biología Molecular, Cinvestav, Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico; (M.S.-L.); (J.M.V.-I.); or (D.L.R.-G.); (A.P.-E.); (J.M.H.-H.)
- Institute for Obesity Research, Monterrey Institute of Technology and Higher Education, Monterrey 64849, Mexico
| | - Carmen Josefina Juárez-Castelán
- Departamento de Genética y Biología Molecular, Cinvestav, Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico; (M.S.-L.); (J.M.V.-I.); or (D.L.R.-G.); (A.P.-E.); (J.M.H.-H.)
| | - Jaime García-Mena
- Departamento de Genética y Biología Molecular, Cinvestav, Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico; (M.S.-L.); (J.M.V.-I.); or (D.L.R.-G.); (A.P.-E.); (J.M.H.-H.)
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Paulinetti AP, Guerieri FF, Augusto IMG, Lazaro CZ, Albanez R, Lovato G, Ratusznei SM, Domingues Rodrigues JA. Thermophilic and mesophilic anaerobic digestion of soybean molasses: A performance vs. stability trade-off. JOURNAL OF ENVIRONMENTAL MANAGEMENT 2024; 370:122508. [PMID: 39366238 DOI: 10.1016/j.jenvman.2024.122508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 09/02/2024] [Accepted: 09/12/2024] [Indexed: 10/06/2024]
Abstract
One of the factors that has a direct impact on anaerobic digestion is the applied organic loading rate (OLRA). Increasing OLRA can boost methane production but can also cause process failure. As a result, establishing the appropriate OLRA for the procedure is critical. This study evaluated the effect of increasing the OLRA using soybean molasses in a thermophilic anaerobic reactor (R-Thermo), as well as the effect of feeding strategy and co-processing with okara. Furthermore, the performance versus stability trade-off between R-Thermo and mesophilic anaerobic digestion (R-Meso) was investigated. The increase of OLRA from 10 to 15 and 20 kg-COD/m³/d led to a decrease in COD removal efficiency (90, 86, and 75%), methane yield (12.0, 11.6, and 9.9 mol-CH4/kg-COD) and an increase in total volatile acids concentration (251, 456, and 1393 mg-HAc/L, respectively). At 15 kg-COD/m³/d, R-Meso performed similarly to R-Thermo, and at 20 kg-COD/m3/d, R-Meso outperformed (81% COD removal efficiency, 9.3 mol-CH4/kg-CODrem and 154.5 mol-CH4/m3/d). Temperature greatly influenced the distribution of metabolic pathways, as shown by thermodynamic and kinetic analyses, thus impacting bacterial diversity. At 55 °C, amongst the bacterial genera, Tepidiphilus stood out (>28.2%), followed by Acetomicrobium, Coprothermobacter and Candidatus_Caldatribacterium. The OLRA clearly impacted the archaeal community; Methanothermobacter (77.4%) was favored over Methanosarcina (14.8%). Under thermophilic temperature, it seems that syntrophic acetate oxidation (SAO) bacteria might have competed for substrate with acetoclastic methanogens, while in R-Meso microorganisms responsible for the initial steps of organic matter breakdown, such as members of the Firmicutes and Proteobacteria phyla (at least 67%), were dominant. In summary, R-Meso, characterized by a more uniform distribution of metabolic pathways, as well as a diverse and well-adapted microbial consortium, have exhibited enhanced stability and outperformed R-Thermo at high-loads.
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Affiliation(s)
- Ana Paula Paulinetti
- Department of Chemical Engineering, Mauá School of Engineering, Mauá Institute of Technology, Praça Mauá 1, Zip Code 09.580-900, São Caetano do Sul/SP, Brazil; Department of Environmental Engineering Sciences, School of Engineering of São Carlos, University of São Paulo, Av. Trabalhador São-Carlense, 400 - Zip Code 13.566-590, São Carlos/SP, Brazil
| | - Fernanda Furtunato Guerieri
- Department of Chemical Engineering, Mauá School of Engineering, Mauá Institute of Technology, Praça Mauá 1, Zip Code 09.580-900, São Caetano do Sul/SP, Brazil
| | - Isabela Mehi Gaspari Augusto
- Department of Chemical Engineering, Mauá School of Engineering, Mauá Institute of Technology, Praça Mauá 1, Zip Code 09.580-900, São Caetano do Sul/SP, Brazil; Department of Environmental Engineering Sciences, School of Engineering of São Carlos, University of São Paulo, Av. Trabalhador São-Carlense, 400 - Zip Code 13.566-590, São Carlos/SP, Brazil
| | - Carolina Zampol Lazaro
- Department of Microbiology, Infectiology and Immunology, University of Montreal, H3C 3J7, Montreal/Quebec, Canada
| | - Roberta Albanez
- Department of Chemical Engineering, Mauá School of Engineering, Mauá Institute of Technology, Praça Mauá 1, Zip Code 09.580-900, São Caetano do Sul/SP, Brazil
| | - Giovanna Lovato
- Department of Chemical Engineering, Mauá School of Engineering, Mauá Institute of Technology, Praça Mauá 1, Zip Code 09.580-900, São Caetano do Sul/SP, Brazil
| | - Suzana Maria Ratusznei
- Department of Chemical Engineering, Mauá School of Engineering, Mauá Institute of Technology, Praça Mauá 1, Zip Code 09.580-900, São Caetano do Sul/SP, Brazil.
| | - José Alberto Domingues Rodrigues
- Department of Chemical Engineering, Mauá School of Engineering, Mauá Institute of Technology, Praça Mauá 1, Zip Code 09.580-900, São Caetano do Sul/SP, Brazil
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Jarmukhanov Z, Mukhanbetzhanov N, Kozhakhmetov S, Nurgaziyev M, Sailybayeva A, Bekbossynova M, Kushugulova A. The association between the gut microbiota metabolite trimethylamine N-oxide and heart failure. Front Microbiol 2024; 15:1440241. [PMID: 39391607 PMCID: PMC11464299 DOI: 10.3389/fmicb.2024.1440241] [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: 05/30/2024] [Accepted: 09/13/2024] [Indexed: 10/12/2024] Open
Abstract
This systematic review explores the relationship between the gut microbiota metabolite trimethylamine N-oxide (TMAO) and heart failure (HF), given the significant impact of TMAO on cardiovascular health. A systematic search and meta-analysis of peer-reviewed studies published from 2013 to 2024 were conducted, focusing on adult patients with heart failure and healthy controls. The review found that elevated levels of TMAO are associated with atherosclerosis, endothelial dysfunction, and increased cardiovascular disease risk, all of which can exacerbate heart failure. The analysis also highlights that high TMAO levels are linked to reduced left ventricular ejection fraction (LVEF) and glomerular filtration rate (GFR), further supporting TMAO's role as a biomarker in heart failure assessment. The findings suggest that interventions targeting gut microbiota to reduce TMAO could potentially benefit patients with heart failure, although further research is needed to evaluate the effectiveness of such approaches.
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Affiliation(s)
- Zharkyn Jarmukhanov
- Laboratory of Microbiome, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | - Nurislam Mukhanbetzhanov
- Laboratory of Microbiome, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | - Samat Kozhakhmetov
- Laboratory of Microbiome, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | - Madiyar Nurgaziyev
- Laboratory of Microbiome, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
| | | | | | - Almagul Kushugulova
- Laboratory of Microbiome, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
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González A, Odriozola I, Fullaondo A, Odriozola A. Microbiota and detrimental protein derived metabolites in colorectal cancer. ADVANCES IN GENETICS 2024; 112:255-308. [PMID: 39396838 DOI: 10.1016/bs.adgen.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Colorectal cancer (CRC) is the third leading cancer in incidence and the second leading cancer in mortality worldwide. There is growing scientific evidence to support the crucial role of the gut microbiota in the development of CRC. The gut microbiota is the complex community of microorganisms that inhabit the host gut in a symbiotic relationship. Diet plays a crucial role in modulating the risk of CRC, with a high intake of red and processed meat being a risk factor for the development of CRC. The production of metabolites derived from protein fermentation by the gut microbiota is considered a crucial element in the interaction between red and processed meat consumption and the development of CRC. This paper examines several metabolites derived from the bacterial fermentation of proteins associated with an increased risk of CRC. These metabolites include ammonia, polyamines, trimethylamine N-oxide (TMAO), N-nitroso compounds (NOC), hydrogen sulphide (H2S), phenolic compounds (p-cresol) and indole compounds (indolimines). These compounds are depicted and reviewed for their association with CRC risk, possible mechanisms promoting carcinogenesis and their relationship with the gut microbiota. Additionally, this paper analyses the evidence related to the role of red and processed meat intake and CRC risk and the factors and pathways involved in bacterial proteolytic fermentation in the large intestine.
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Affiliation(s)
- Adriana González
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain.
| | - Iñaki Odriozola
- Health Department of Basque Government, Donostia-San Sebastián, Spain
| | - Asier Fullaondo
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Adrian Odriozola
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
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12
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Liu J, Zhang T, Liu X, Wang Q, Zhang H. Causal effect between gut microbiota and gastroesophageal reflux disease: a bidirectional two-sample Mendelian randomization study. Eur J Gastroenterol Hepatol 2024; 36:875-883. [PMID: 38625824 DOI: 10.1097/meg.0000000000002774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/18/2024]
Abstract
Previous observational studies have found that the gut microbiota is closely related to the pathogenesis of gastroesophageal reflux disease (GERD), while their causal relationship is unclear. A two-sample multivariate Mendelian randomization analysis was implemented to estimate the causal effect of gut microbiota on GERD. The gut microbiota aggregated statistics were derived from a meta-analysis of the largest available genome-wide association studies (GWAS) conducted by the MiBioGen alliance ( n = 13 266). GERD aggregated statistics were derived from published GWAS (129 080 cases and 473 524 controls). A bidirectional two-sample Mendelian randomization study was conducted to explore the causal relationship between gut microbiota and GERD using the inverse variance weighted (IVW), Mendelian randomization Egger, single model, weighted median, and weighted model. To verify the stability of the main results of Mendelian randomization analysis, we performed sensitivity analysis. Based on the results of IVW, we found that Anaerostipes was causally associated with an increased risk of GERD [odds ratio (OR): 1.09, P = 0.018]. Eight gut microbiota taxa ( Actinobacteria, Bifidobacteriales, Bifidobacteriaceae, Clostridiales vadin BB60 group, Rikenellaceae, Lachnospiraceae UCG004, Methanobrevibacter , and unknown genus id.1000000073 ) are predicted to act causally in suppressing the risk of GERD ( P < 0.05). In addition, reverse Mendelian randomization analyses revealed that the abundance of 15 gut microbiota taxon was found to be affected by GERD. No significant estimation of heterogeneity or pleiotropy is detected. Our study presents a complicated causal relationship between gut microbiota and GERD that offers guidance on the selection of appropriate probiotics as clinical interventions for GERD.
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Affiliation(s)
- Jingyu Liu
- Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China
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Cena JAD, Belmok A, Kyaw CM, Dame-Teixeira N. The Archaea domain: Exploring historical and contemporary perspectives with in silico primer coverage analysis for future research in Dentistry. Arch Oral Biol 2024; 161:105936. [PMID: 38422909 DOI: 10.1016/j.archoralbio.2024.105936] [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: 01/13/2024] [Revised: 02/07/2024] [Accepted: 02/21/2024] [Indexed: 03/02/2024]
Abstract
OBJECTIVE The complete picture of how the human microbiome interacts with its host is still largely unknown, particularly concerning microorganisms beyond bacteria. Although existing in very low abundance and not directly linked to causing diseases, archaea have been detected in various sites of the human body, including the gastrointestinal tract, oral cavity, skin, eyes, respiratory and urinary systems. But what exactly are these microorganisms? In the early 1990 s, archaea were classified as a distinct domain of life, sharing a more recent common ancestor with eukaryotes than with bacteria. While archaea's presence and potential significance in Dentistry remain under-recognized, there are concerns that they may contribute to oral dysbiosis. However, detecting archaea in oral samples presents challenges, including difficulties in culturing, the selection of DNA extraction methods, primer design, bioinformatic analysis, and databases. DESIGN This is a comprehensive review on the oral archaeome, presenting an in-depth in silico analysis of various primers commonly used for detecting archaea in human body sites. RESULTS Among several primer pairs used for detecting archaea in human samples across the literature, only one specifically designed for detecting methanogenic archaea in stool samples, exhibited exceptional coverage levels for the domain and various archaea phyla. CONCLUSIONS Our in silico analysis underscores the need for designing new primers targeting not only methanogenic archaea but also nanoarchaeal and thaumarchaeota groups to gain a comprehensive understanding of the archaeal oral community. By doing so, researchers can pave the way for further advancements in the field of oral archaeome research.
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Affiliation(s)
| | - Aline Belmok
- Institute of Biology, University of Brasilia, Brazil
| | | | - Naile Dame-Teixeira
- Department of Dentistry, School of Health Sciences, University of Brasilia, Brazil; Division of Oral Biology, School of Dentistry, University of Leeds, UK.
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14
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Liu X, Mo J, Yang X, Peng L, Zeng Y, Zheng Y, Song G. Causal relationship between gut microbiota and chronic renal failure: a two-sample Mendelian randomization study. Front Microbiol 2024; 15:1356478. [PMID: 38633704 PMCID: PMC11021586 DOI: 10.3389/fmicb.2024.1356478] [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: 12/19/2023] [Accepted: 03/20/2024] [Indexed: 04/19/2024] Open
Abstract
Background Observational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure. Methods Employing genome-wide association study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings. Results According to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71-0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08-1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02-1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03-1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00-1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02-1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09-1.28, p < 0.001) may be risk factors for chronic renal failure. However, after correction for multiple comparisons using False Discovery Rate, only the associations with Escherichia-Shigella and Howardella remain significant, indicating that the other genera have suggestive associations. Sensitivity analyses did not reveal any pleiotropy or heterogeneity. Conclusion Our two-sample Mendelian randomization study suggests that the genera Escherichia-Shigella and Howardella are risk factors for chronic renal failure, and they may serve as potential targets for future therapeutic interventions. However, the exact mechanisms of action are not yet clear, necessitating further research to elucidate their precise roles fully.
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Affiliation(s)
- Xingzheng Liu
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Jinying Mo
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Xuerui Yang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Ling Peng
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Youjia Zeng
- Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Yihou Zheng
- Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Gaofeng Song
- Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
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Ni S, Lv W, Ji Z, Wang K, Mei Y, Li Y. Progress of Crude Oil Gasification Technology Assisted by Microorganisms in Reservoirs. Microorganisms 2024; 12:702. [PMID: 38674646 PMCID: PMC11051786 DOI: 10.3390/microorganisms12040702] [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: 02/22/2024] [Revised: 03/17/2024] [Accepted: 03/26/2024] [Indexed: 04/28/2024] Open
Abstract
Crude oil gasification bacteria, including fermenting bacteria, hydrocarbon-oxidizing bacteria, reducing bacteria, and methanogenic bacteria, participate in multi-step reactions involving initial activation, intermediate metabolism, and the methanogenesis of crude oil hydrocarbons. These bacteria degrade crude oil into smaller molecules such as hydrogen, carbon dioxide, acetic acid, and formic acid. Ultimately, they convert it into methane, which can be utilized or stored as a strategic resource. However, the current challenges in crude oil gasification include long production cycles and low efficiency. This paper provides a summary of the microbial flora involved in crude oil gasification, the gasification metabolism pathways within reservoirs, and other relevant information. It specifically focuses on analyzing the factors that affect the efficiency of crude oil gasification metabolism and proposes suggestions for improving this efficiency. These studies deepen our understanding of the potential of reservoir ecosystems and provide valuable insights for future reservoir development and management.
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Affiliation(s)
- Shumin Ni
- University of Chinese Academy of Sciences, Beijing 100049, China; (S.N.); (K.W.); (Y.M.); (Y.L.)
- Institute of Porous Flow & Fluid Mechanics, Chinese Academy of Sciences, Langfang 065007, China;
| | - Weifeng Lv
- Institute of Porous Flow & Fluid Mechanics, Chinese Academy of Sciences, Langfang 065007, China;
- State Key Laboratory of Enhanced Oil Recovery, Research Institute of Petroleum Exploration and Development, CNPC, Beijing 100083, China
| | - Zemin Ji
- Institute of Porous Flow & Fluid Mechanics, Chinese Academy of Sciences, Langfang 065007, China;
| | - Kai Wang
- University of Chinese Academy of Sciences, Beijing 100049, China; (S.N.); (K.W.); (Y.M.); (Y.L.)
- Institute of Porous Flow & Fluid Mechanics, Chinese Academy of Sciences, Langfang 065007, China;
| | - Yuhao Mei
- University of Chinese Academy of Sciences, Beijing 100049, China; (S.N.); (K.W.); (Y.M.); (Y.L.)
- Institute of Porous Flow & Fluid Mechanics, Chinese Academy of Sciences, Langfang 065007, China;
| | - Yushu Li
- University of Chinese Academy of Sciences, Beijing 100049, China; (S.N.); (K.W.); (Y.M.); (Y.L.)
- Institute of Porous Flow & Fluid Mechanics, Chinese Academy of Sciences, Langfang 065007, China;
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Vita AA, Roberts KM, Gundersen A, Farris Y, Zwickey H, Bradley R, Weir TL. Relationships between Habitual Polyphenol Consumption and Gut Microbiota in the INCLD Health Cohort. Nutrients 2024; 16:773. [PMID: 38542685 PMCID: PMC10974568 DOI: 10.3390/nu16060773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/01/2024] [Accepted: 03/05/2024] [Indexed: 04/01/2024] Open
Abstract
While polyphenol consumption is often associated with an increased abundance of beneficial microbes and decreased opportunistic pathogens, these relationships are not completely described for polyphenols consumed via habitual diet, including culinary herb and spice consumption. This analysis of the International Cohort on Lifestyle Determinants of Health (INCLD Health) cohort uses a dietary questionnaire and 16s microbiome data to examine relationships between habitual polyphenol consumption and gut microbiota in healthy adults (n = 96). In this exploratory analysis, microbial taxa, but not diversity measures, differed by levels of dietary polyphenol consumption. Taxa identified as exploratory biomarkers of daily polyphenol consumption (mg/day) included Lactobacillus, Bacteroides, Enterococcus, Eubacterium ventriosum group, Ruminococcus torques group, and Sutterella. Taxa identified as exploratory biomarkers of the frequency of polyphenol-weighted herb and spice use included Lachnospiraceae UCG-001, Lachnospiraceae UCG-004, Methanobrevibacter, Lachnoclostridium, and Lachnotalea. Several of the differentiating taxa carry out activities important for human health, although out of these taxa, those with previously described pro-inflammatory qualities in certain contexts displayed inverse relationships with polyphenol consumption. Our results suggest that higher quantities of habitual polyphenol consumption may support an intestinal environment where opportunistic and pro-inflammatory bacteria are represented in a lower relative abundance compared to those with less potentially virulent qualities.
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Affiliation(s)
- Alexandra Adorno Vita
- Helfgott Research Institute, National University of Natural Medicine, Portland, OR 97201, USA
- Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523, USA
| | - Kristen M. Roberts
- School of Health and Rehabilitation Sciences, Ohio State University, Columbus, OH 43210, USA
| | - Anders Gundersen
- Helfgott Research Institute, National University of Natural Medicine, Portland, OR 97201, USA
| | - Yuliya Farris
- Pacific Northwest National Laboratory, Biological Sciences Division, Richland, WA 99352, USA
| | - Heather Zwickey
- Helfgott Research Institute, National University of Natural Medicine, Portland, OR 97201, USA
| | - Ryan Bradley
- Helfgott Research Institute, National University of Natural Medicine, Portland, OR 97201, USA
- Herbert Wertheim School of Public Health, University of California, San Diego, CA 92037, USA
| | - Tiffany L. Weir
- Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523, USA
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Cisek AA, Szymańska E, Aleksandrzak-Piekarczyk T, Cukrowska B. The Role of Methanogenic Archaea in Inflammatory Bowel Disease-A Review. J Pers Med 2024; 14:196. [PMID: 38392629 PMCID: PMC10890621 DOI: 10.3390/jpm14020196] [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: 12/31/2023] [Revised: 01/28/2024] [Accepted: 02/08/2024] [Indexed: 02/24/2024] Open
Abstract
Methanogenic archaea are a part of the commensal gut microbiota responsible for hydrogen sink and the efficient production of short-chain fatty acids. Dysbiosis of methanogens is suspected to play a role in pathogenesis of variety of diseases, including inflammatory bowel disease (IBD). Unlike bacteria, the diversity of archaea seems to be higher in IBD patients compared to healthy subjects, whereas the prevalence and abundance of gut methanogens declines in IBD, especially in ulcerative colitis. To date, studies focusing on methanogens in pediatric IBD are very limited; nevertheless, the preliminary results provide some evidence that methanogens may be influenced by the chronic inflammatory process in IBD. In this review, we demonstrated the development and diversity of the methanogenic community in IBD, both in adults and children.
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Affiliation(s)
- Agata Anna Cisek
- Department of Pathomorphology, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Edyta Szymańska
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | | | - Bożena Cukrowska
- Department of Pathomorphology, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
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Yue Y, Cui HB, Chu YJ, Zheng GL. Efficacy of Spleen-and-Stomach-Tonifying, Yin-Fire-Purging, and Yang-Raising Decoction Derived from the Trimethylamine N-Oxide Metabolic Pathway of Intestinal Microbiota on Macrovascular Lesions Caused by Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2024; 17:585-596. [PMID: 38347910 PMCID: PMC10859761 DOI: 10.2147/dmso.s431435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 01/11/2024] [Indexed: 02/15/2024] Open
Abstract
Objective We aimed to analyze the mechanisms underlying spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction derived from the trimethylamine N-oxide (TMAO) metabolic pathway of intestinal microbiota in the treatment of macrovascular lesions caused by type 2 diabetes mellitus (T2DM). Methods Hartley-guinea pigs were randomly divided into 3 groups-the blank, model, and intervention groups. The T2DM combined with atherosclerosis guinea pig models were established in the model and intervention groups. After successful modeling, spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction were administered intragastrically to the intervention group, while the same volume of normal saline was administered via gavage to the blank and model groups. After 6 weeks of continuous gavage, guinea pigs were sacrificed in all groups, the colon contents were obtained, and the diversity and structural differences of intestinal microbiota were analyzed via bioinformatics. Serum was collected to detect differences in lipids, TMAO, oxidative stress, and inflammation markers between groups. Results Compared to the blank group, the species diversity of the intestinal microbiota in the model and intervention groups was significantly reduced. Based on the results of Analysis of Similarities and Multiple Response Permutation Procedure, the microbiota structure of the intervention group was closer to that of the blank group. After modeling, the blood lipid levels of guinea pigs increased significantly, and drug intervention significantly reduced the levels of TC, TG, and LDL-C (P < 0.05). TMAO expression was significantly increased after modeling (P < 0.05), while drug intervention reduced TMAO expression (P < 0.05). Compared to the model group, drug intervention significantly increased the concentrations of SOD while decreasing the concentrations of MDA, ICAM-1, VCAM-1, IL-6, and hs-CRP. Conclusion Spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction can reduce the risk of macrovascular lesions in T2DM, and its mechanism may be associated with its ability to regulate the TMAO metabolic pathway of intestinal microbiota.
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Affiliation(s)
- Yue Yue
- Department of Endocrinology, The 983 Hospital of the Joint Logistics Force of the Chinese People’s Liberation Army, Tianjin, People’s Republic of China
| | - Han-Bo Cui
- Department of Diabetes, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, People’s Republic of China
| | - Yue-Jie Chu
- Department of Diabetes, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, People’s Republic of China
| | - Gui-Ling Zheng
- Department of Endocrinology, The 983 Hospital of the Joint Logistics Force of the Chinese People’s Liberation Army, Tianjin, People’s Republic of China
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Wang W, Dong Y, Guo W, Zhang X, Degen AA, Bi S, Ding L, Chen X, Long R. Linkages between rumen microbiome, host, and environment in yaks, and their implications for understanding animal production and management. Front Microbiol 2024; 15:1301258. [PMID: 38348184 PMCID: PMC10860762 DOI: 10.3389/fmicb.2024.1301258] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 01/03/2024] [Indexed: 02/15/2024] Open
Abstract
Livestock on the Qinghai-Tibetan Plateau is of great importance for the livelihood of the local inhabitants and the ecosystem of the plateau. The natural, harsh environment has shaped the adaptations of local livestock while providing them with requisite eco-services. Over time, unique genes and metabolic mechanisms (nitrogen and energy) have evolved which enabled the yaks to adapt morphologically and physiologically to the Qinghai-Tibetan Plateau. The rumen microbiota has also co-evolved with the host and contributed to the host's adaptation to the environment. Understanding the complex linkages between the rumen microbiota, the host, and the environment is essential to optimizing the rumen function to meet the growing demands for animal products while minimizing the environmental impact of ruminant production. However, little is known about the mechanisms of host-rumen microbiome-environment linkages and how they ultimately benefit the animal in adapting to the environment. In this review, we pieced together the yak's adaptation to the Qinghai-Tibetan Plateau ecosystem by summarizing the natural selection and nutritional features of yaks and integrating the key aspects of its rumen microbiome with the host metabolic efficiency and homeostasis. We found that this homeostasis results in higher feed digestibility, higher rumen microbial protein production, higher short-chain fatty acid (SCFA) concentrations, and lower methane emissions in yaks when compared with other low-altitude ruminants. The rumen microbiome forms a multi-synergistic relationship among the rumen microbiota services, their communities, genes, and enzymes. The rumen microbial proteins and SCFAs act as precursors that directly impact the milk composition or adipose accumulation, improving the milk or meat quality, resulting in a higher protein and fat content in yak milk and a higher percentage of protein and abundant fatty acids in yak meat when compared to dairy cow or cattle. The hierarchical interactions between the climate, forage, rumen microorganisms, and host genes have reshaped the animal's survival and performance. In this review, an integrating and interactive understanding of the host-rumen microbiome environment was established. The understanding of these concepts is valuable for agriculture and our environment. It also contributes to a better understanding of microbial ecology and evolution in anaerobic ecosystems and the host-environment linkages to improve animal production.
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Affiliation(s)
- Weiwei Wang
- Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang, Guizhou, China
- State Key Laboratory of Grassland Agro-Ecosystems, College of Ecology, Lanzhou University, Lanzhou, China
| | - Yuntao Dong
- Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang, Guizhou, China
| | - Wei Guo
- Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang, Guizhou, China
- State Key Laboratory of Grassland Agro-Ecosystems, College of Ecology, Lanzhou University, Lanzhou, China
| | - Xiao Zhang
- Tianjin Key Laboratory of Conservation and Utilization of Animal Diversity, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - A. Allan Degen
- Desert Animal Adaptations and Husbandry, Wyler Department of Dryland Agriculture, Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Sisi Bi
- State Key Laboratory of Grassland Agro-Ecosystems, College of Ecology, Lanzhou University, Lanzhou, China
| | - Luming Ding
- State Key Laboratory of Grassland Agro-Ecosystems, College of Ecology, Lanzhou University, Lanzhou, China
| | - Xiang Chen
- Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang, Guizhou, China
| | - Ruijun Long
- State Key Laboratory of Grassland Agro-Ecosystems, College of Ecology, Lanzhou University, Lanzhou, China
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20
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Xie F, Zhao S, Zhan X, Zhou Y, Li Y, Zhu W, Pope PB, Attwood GT, Jin W, Mao S. Unraveling the phylogenomic diversity of Methanomassiliicoccales and implications for mitigating ruminant methane emissions. Genome Biol 2024; 25:32. [PMID: 38263062 PMCID: PMC10804542 DOI: 10.1186/s13059-024-03167-0] [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: 03/14/2023] [Accepted: 01/07/2024] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Methanomassiliicoccales are a recently identified order of methanogens that are diverse across global environments particularly the gastrointestinal tracts of animals; however, their metabolic capacities are defined via a limited number of cultured strains. RESULTS Here, we profile and analyze 243 Methanomassiliicoccales genomes assembled from cultured representatives and uncultured metagenomes recovered from various biomes, including the gastrointestinal tracts of different animal species. Our analyses reveal the presence of numerous undefined genera and genetic variability in metabolic capabilities within Methanomassiliicoccales lineages, which is essential for adaptation to their ecological niches. In particular, gastrointestinal tract Methanomassiliicoccales demonstrate the presence of co-diversified members with their hosts over evolutionary timescales and likely originated in the natural environment. We highlight the presence of diverse clades of vitamin transporter BtuC proteins that distinguish Methanomassiliicoccales from other archaeal orders and likely provide a competitive advantage in efficiently handling B12. Furthermore, genome-centric metatranscriptomic analysis of ruminants with varying methane yields reveal elevated expression of select Methanomassiliicoccales genera in low methane animals and suggest that B12 exchanges could enable them to occupy ecological niches that possibly alter the direction of H2 utilization. CONCLUSIONS We provide a comprehensive and updated account of divergent Methanomassiliicoccales lineages, drawing from numerous uncultured genomes obtained from various habitats. We also highlight their unique metabolic capabilities involving B12, which could serve as promising targets for mitigating ruminant methane emissions by altering H2 flow.
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Affiliation(s)
- Fei Xie
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Shengwei Zhao
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Xiaoxiu Zhan
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Yang Zhou
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Yin Li
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Weiyun Zhu
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Phillip B Pope
- Department of Animal and Aquacultural Sciences, Faculty of Biosciences, Norwegian University of Life Sciences, Ås, Norway
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway
| | - Graeme T Attwood
- AgResearch Limited, Grasslands Research Centre, Palmerston North, New Zealand
| | - Wei Jin
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
| | - Shengyong Mao
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
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Guerra A. Human associated Archaea: a neglected microbiome worth investigating. World J Microbiol Biotechnol 2024; 40:60. [PMID: 38172371 DOI: 10.1007/s11274-023-03842-7] [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: 07/22/2023] [Accepted: 11/14/2023] [Indexed: 01/05/2024]
Abstract
The majority of research in the field of human microbiota has predominantly focused on bacterial and fungal communities. Conversely, the human archaeome has received scant attention and remains poorly studied, despite its potential role in human diseases. Archaea have the capability to colonize various human body sites, including the gastrointestinal tract, skin, vagina, breast milk, colostrum, urinary tract, lungs, nasal and oral cavities. This colonization can occur through vertical transmission, facilitated by the transfer of breast milk or colostrum from mother to child, as well as through the consumption of dairy products, organic produce, salty foods, and fermented items. The involvement of these microorganisms in diseases, such as periodontitis, might be attributed to their production of toxic compounds and the detoxification of growth inhibitors for pathogens. However, the precise mechanisms through which these contributions occur remain incompletely understood, necessitating further studies to assess their impact on human health.
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Zeng Z, Qiu J, Chen Y, Liang D, Wei F, Fu Y, Zhang J, Wei X, Zhang X, Tao J, Lin L, Zheng J. Altered Gut Microbiota as a Potential Risk Factor for Coronary Artery Disease in Diabetes: A Two-Sample Bi-Directional Mendelian Randomization Study. Int J Med Sci 2024; 21:376-395. [PMID: 38169662 PMCID: PMC10758148 DOI: 10.7150/ijms.92131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 12/08/2023] [Indexed: 01/05/2024] Open
Abstract
The current body of research points to a notable correlation between an imbalance in gut microbiota and the development of type 2 diabetes mellitus (T2D) as well as its consequential ailment, coronary artery disease (CAD). The complexities underlying the association, especially in the context of diabetic coronary artery disease (DCAD), are not yet fully understood, and the causal links require further clarification. In this study, a bidirectional Mendelian randomization (MR) methodology was utilized to explore the causal relationships between gut microbiota, T2D, and CAD. By analyzing data from the DIAGRAM, GERA, UKB, FHS, and mibioGen cohorts and examining GWAS databases, we sought to uncover genetic variants linked to T2D, CAD, and variations in gut microbiota and metabolites, aiming to shed light on the potential mechanisms connecting gut microbiota with DCAD. Our investigation uncovered a marked causal link between the presence of Oxalobacter formigenes and an increased incidence of both T2D and CAD. Specifically, a ten-unit genetic predisposition towards T2D was found to be associated with a 6.1% higher probability of an increase in the Oxalobacteraceae family's presence (β = 0.061, 95% CI = 0.002-0.119). In a parallel finding, an augmented presence of Oxalobacter was related to an 8.2% heightened genetic likelihood of CAD (β = 0.082, 95% CI = 0.026-0.137). This evidence indicates a critical pathway by which T2D can potentially raise the risk of CAD via alterations in gut microbiota. Additionally, our analyses reveal a connection between CAD risk and Methanobacteria, thus providing fresh perspectives on the roles of TMAO and carnitine in the etiology of CAD. The data also suggest a direct causal relationship between increased levels of certain metabolites - proline, lysophosphatidylcholine, asparagine, and salicylurate - and the prevalence of both T2D and CAD. Sensitivity assessments reinforce the notion that changes in Oxalobacter formigenes could pose a risk for DCAD. There is also evidence to suggest that DCAD may, in turn, affect the gut microbiota's makeup. Notably, a surge in serum TMAO levels in individuals with CAD, coinciding with a reduced presence of methanogens, has been identified as a potentially significant factor for future examination.
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Affiliation(s)
- Zhaopei Zeng
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junxiong Qiu
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yu Chen
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Diefei Liang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Feng Wei
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Cardiothoracic Surgery, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, China
| | - Yuan Fu
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiarui Zhang
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiexiao Wei
- Department of Cardiology, Chinese PLA General Hospital, Beijing, China
| | - Xinyi Zhang
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jun Tao
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Liling Lin
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junmeng Zheng
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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Borrel G, Fadhlaoui K, Ben Hania W, Gaci N, Pehau-Arnaudet G, Chaudhary PP, Vandekerckove P, Ballet N, Alric M, O’Toole PW, Fardeau ML, Ollivier B, Brugère JF. Methanomethylophilus alvi gen. nov., sp. nov., a Novel Hydrogenotrophic Methyl-Reducing Methanogenic Archaea of the Order Methanomassiliicoccales Isolated from the Human Gut and Proposal of the Novel Family Methanomethylophilaceae fam. nov. Microorganisms 2023; 11:2794. [PMID: 38004804 PMCID: PMC10673518 DOI: 10.3390/microorganisms11112794] [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: 10/28/2023] [Revised: 11/09/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
The methanogenic strain Mx-05T was isolated from the human fecal microbiome. A phylogenetic analysis based on the 16S rRNA gene and protein marker genes indicated that the strain is affiliated with the order Methanomassiliicoccales. It shares 86.9% 16S rRNA gene sequence identity with Methanomassiliicoccus luminyensis, the only member of this order previously isolated. The cells of Mx-05T were non-motile cocci, with a diameter range of 0.4-0.7 μm. They grew anaerobically and reduced methanol, monomethylamine, dimethylamine, and trimethylamine into methane, using H2 as an electron donor. H2/CO2, formate, ethanol, and acetate were not used as energy sources. The growth of Mx-05T required an unknown medium factor(s) provided by Eggerthella lenta and present in rumen fluid. Mx-05T grew between 30 °C and 40 °C (optimum 37 °C), over a pH range of 6.9-8.3 (optimum pH 7.5), and between 0.02 and 0.34 mol.L-1 NaCl (optimum 0.12 mol.L-1 NaCl). The genome is 1.67 Mbp with a G+C content of 55.5 mol%. Genome sequence annotation confirmed the absence of the methyl branch of the H4MPT Wood-Ljungdahl pathway, as described for other Methanomassiliicoccales members. Based on an average nucleotide identity analysis, we propose strain Mx-05T as being a novel representative of the order Methanomassiliicoccales, within the novel family Methanomethylophilaceae, for which the name Methanomethylophilus alvi gen. nov, sp. nov. is proposed. The type strain is Mx-05T (JCM 31474T).
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Affiliation(s)
- Guillaume Borrel
- Institut Pasteur, Université Paris Cité, Evolutionary Biology of the Microbial Cell, 75015 Paris, France
| | - Khaled Fadhlaoui
- Aix Marseille Univ., Université de Toulon, CNRS, IRD, MIO, 13288 Marseille, France; (K.F.); (B.O.)
- Université Clermont Auvergne, INRA, MEDIS, 63000 Clermont-Ferrand, France
- Université Clermont Auvergne, CNRS, UMR 6023 CNRS-UCA, Laboratoire Microorganismes: Génome et Environnement LMGE, 63000 Clermont-Ferrand, France
| | - Wajdi Ben Hania
- Aix Marseille Univ., Université de Toulon, CNRS, IRD, MIO, 13288 Marseille, France; (K.F.); (B.O.)
- Université d’Auvergne, EA CIDAM, 63000 Clermont-Ferrand, France (J.-F.B.)
| | - Nadia Gaci
- Université d’Auvergne, EA CIDAM, 63000 Clermont-Ferrand, France (J.-F.B.)
| | - Gérard Pehau-Arnaudet
- Institut Pasteur, Université Paris Cité, Ultrastructural Bioimaging, 75015 Paris, France
| | - Prem Prashant Chaudhary
- Université d’Auvergne, EA CIDAM, 63000 Clermont-Ferrand, France (J.-F.B.)
- Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | | | - Nathalie Ballet
- Lesaffre International, Lesaffre Group, 59700 Marcq-en-Barœul, France
| | - Monique Alric
- Université d’Auvergne, EA CIDAM, 63000 Clermont-Ferrand, France (J.-F.B.)
| | | | - Marie-Laure Fardeau
- Aix Marseille Univ., Université de Toulon, CNRS, IRD, MIO, 13288 Marseille, France; (K.F.); (B.O.)
| | - Bernard Ollivier
- Aix Marseille Univ., Université de Toulon, CNRS, IRD, MIO, 13288 Marseille, France; (K.F.); (B.O.)
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Wu X, Li Q, Cai J, Huang H, Ma S, Tan H. Longitudinal change of gut microbiota in hypertensive disorders in pregnancy: a nested case-control and Mendelian randomization study. Sci Rep 2023; 13:16986. [PMID: 37813882 PMCID: PMC10562506 DOI: 10.1038/s41598-023-43780-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 09/28/2023] [Indexed: 10/11/2023] Open
Abstract
Mounting evidence has shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP), however, most studies only focused on one time point in pregnancy. In this study, we conducted a nested case-control study utilizing a follow-up cohort, resulting in the collection of 47 HDP patients and 30 healthy controls. The GM profiles were explored using 16S rRNA sequencing at three time points during pregnancy. The diversity analysis of GM showed no significant difference between HDP patients and controls, however, we found 21 differential GM during pregnancy. Trend analysis showed that there are statistical differences in the relative abundance of Thermomonas, Xanthomonas, and Phenylobacteriumat during pregnancy in the gestational hypertension group, and of Xanthomonas, Polycyclovorans, and Phenylobacterium in the control group. The correlation study found that six genera of GM are related to blood pressure. Furthermore, the MR analysis identified the causal relationship between Methanobrevibacter and pre-eclampsia (PE). This study first explored the longitudinal change of GM in HDP patients during pregnancy, found the differential GM, and detected the causal association. Our findings may promote the prevention and treatment of HDP from the perspective of GM and provide valuable insights into the pathogenesis of HDP.
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Affiliation(s)
- Xinrui Wu
- School of Medicine, Jishou University, Jishou, China
- Xiangya School of Public Health, Central South University, Changsha, China
| | - Qi Li
- Xiangxi Center for Disease Control and Prevention, Jishou, China
| | - Jiawang Cai
- School of Medicine, Jishou University, Jishou, China
| | | | - Shujuan Ma
- Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China.
| | - Hongzhuan Tan
- Xiangya School of Public Health, Central South University, Changsha, China.
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Ciccone MM, Lepera ME, Guaricci AI, Forleo C, Cafiero C, Colella M, Palmirotta R, Santacroce L. Might Gut Microbiota Be a Target for a Personalized Therapeutic Approach in Patients Affected by Atherosclerosis Disease? J Pers Med 2023; 13:1360. [PMID: 37763128 PMCID: PMC10532785 DOI: 10.3390/jpm13091360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/01/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023] Open
Abstract
In recent years, the increasing number of studies on the relationship between the gut microbiota and atherosclerosis have led to significant interest in this subject. The gut microbiota, its metabolites (metabolome), such as TMAO, and gut dysbiosis play an important role in the development of atherosclerosis. Furthermore, inflammation, originating from the intestinal tract, adds yet another mechanism by which the human ecosystem is disrupted, resulting in the manifestation of metabolic diseases and, by extension, cardiovascular diseases. The scientific community must understand and elucidate these mechanisms in depth, to gain a better understanding of the relationship between atherosclerosis and the gut microbiome and to promote the development of new therapeutic targets in the coming years. This review aims to present the knowledge acquired so far, to trigger others to further investigate this intriguing topic.
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Affiliation(s)
- Marco Matteo Ciccone
- Cardiology Unit, Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (M.M.C.); (M.E.L.); (A.I.G.); (C.F.)
| | - Mario Erminio Lepera
- Cardiology Unit, Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (M.M.C.); (M.E.L.); (A.I.G.); (C.F.)
| | - Andrea Igoren Guaricci
- Cardiology Unit, Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (M.M.C.); (M.E.L.); (A.I.G.); (C.F.)
| | - Cinzia Forleo
- Cardiology Unit, Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (M.M.C.); (M.E.L.); (A.I.G.); (C.F.)
| | - Concetta Cafiero
- Area of Molecular Pathology, Anatomic Pathology Unit, Fabrizio Spaziani Hospital, 03100 Frosinone, Italy;
| | - Marica Colella
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (M.C.); (L.S.)
| | - Raffele Palmirotta
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (M.C.); (L.S.)
| | - Luigi Santacroce
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (M.C.); (L.S.)
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Volmer JG, McRae H, Morrison M. The evolving role of methanogenic archaea in mammalian microbiomes. Front Microbiol 2023; 14:1268451. [PMID: 37727289 PMCID: PMC10506414 DOI: 10.3389/fmicb.2023.1268451] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 08/18/2023] [Indexed: 09/21/2023] Open
Abstract
Methanogenic archaea (methanogens) represent a diverse group of microorganisms that inhabit various environmental and host-associated microbiomes. These organisms play an essential role in global carbon cycling given their ability to produce methane, a potent greenhouse gas, as a by-product of their energy production. Recent advances in culture-independent and -dependent studies have highlighted an increased prevalence of methanogens in the host-associated microbiome of diverse animal species. Moreover, there is increasing evidence that methanogens, and/or the methane they produce, may play a substantial role in human health and disease. This review addresses the expanding host-range and the emerging view of host-specific adaptations in methanogen biology and ecology, and the implications for host health and disease.
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Affiliation(s)
- James G. Volmer
- Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, QLD, Australia
| | - Harley McRae
- Faculty of Medicine, University of Queensland Frazer Institute, Translational Research Institute, Woolloongabba, QLD, Australia
| | - Mark Morrison
- Faculty of Medicine, University of Queensland Frazer Institute, Translational Research Institute, Woolloongabba, QLD, Australia
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Aparici-Carratalá D, Esclapez J, Bautista V, Bonete MJ, Camacho M. Archaea: current and potential biotechnological applications. Res Microbiol 2023; 174:104080. [PMID: 37196775 DOI: 10.1016/j.resmic.2023.104080] [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: 01/29/2023] [Revised: 05/08/2023] [Accepted: 05/10/2023] [Indexed: 05/19/2023]
Abstract
Archaea are microorganisms with great ability to colonize some of the most inhospitable environments in nature, managing to survive in places with extreme characteristics for most microorganisms. Its proteins and enzymes are stable and can act under extreme conditions in which other proteins and enzymes would degrade. These attributes make them ideal candidates for use in a wide range of biotechnological applications. This review describes the most important applications, both current and potential, that archaea present in Biotechnology, classifying them according to the sector to which the application is directed. It also analyzes the advantages and disadvantages of its use.
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Affiliation(s)
- David Aparici-Carratalá
- Department of Biochemistry and Molecular Biology and Soil Science and Agricultural Chemistry, Biochemistry and Molecular Biology Area, Faculty of Science, University of Alicante, Carretera de San Vicente del Raspeig s/n, San Vicente del Raspeig, Alicante, 03690, Spain.
| | - Julia Esclapez
- Department of Biochemistry and Molecular Biology and Soil Science and Agricultural Chemistry, Biochemistry and Molecular Biology Area, Faculty of Science, University of Alicante, Carretera de San Vicente del Raspeig s/n, San Vicente del Raspeig, Alicante, 03690, Spain.
| | - Vanesa Bautista
- Department of Biochemistry and Molecular Biology and Soil Science and Agricultural Chemistry, Biochemistry and Molecular Biology Area, Faculty of Science, University of Alicante, Carretera de San Vicente del Raspeig s/n, San Vicente del Raspeig, Alicante, 03690, Spain.
| | - María-José Bonete
- Department of Biochemistry and Molecular Biology and Soil Science and Agricultural Chemistry, Biochemistry and Molecular Biology Area, Faculty of Science, University of Alicante, Carretera de San Vicente del Raspeig s/n, San Vicente del Raspeig, Alicante, 03690, Spain.
| | - Mónica Camacho
- Department of Biochemistry and Molecular Biology and Soil Science and Agricultural Chemistry, Biochemistry and Molecular Biology Area, Faculty of Science, University of Alicante, Carretera de San Vicente del Raspeig s/n, San Vicente del Raspeig, Alicante, 03690, Spain.
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Feehan B, Ran Q, Dorman V, Rumback K, Pogranichniy S, Ward K, Goodband R, Niederwerder MC, Lee STM. Novel complete methanogenic pathways in longitudinal genomic study of monogastric age-associated archaea. Anim Microbiome 2023; 5:35. [PMID: 37461084 DOI: 10.1186/s42523-023-00256-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 07/11/2023] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND Archaea perform critical roles in the microbiome system, including utilizing hydrogen to allow for enhanced microbiome member growth and influencing overall host health. With the majority of microbiome research focusing on bacteria, the functions of archaea are largely still under investigation. Understanding methanogenic functions during the host lifetime will add to the limited knowledge on archaeal influence on gut and host health. In our study, we determined lifelong archaea dynamics, including detection and methanogenic functions, while assessing global, temporal and host distribution of our novel archaeal metagenome-assembled genomes (MAGs). We followed 7 monogastric swine throughout their life, from birth to adult (1-156 days of age), and collected feces at 22 time points. The samples underwent gDNA extraction, Illumina sequencing, bioinformatic quality and assembly processes, MAG taxonomic assignment and functional annotation. MAGs were utilized in downstream phylogenetic analysis for global, temporal and host distribution in addition to methanogenic functional potential determination. RESULTS We generated 1130 non-redundant MAGs, representing 588 unique taxa at the species level, with 8 classified as methanogenic archaea. The taxonomic classifications were as follows: orders Methanomassiliicoccales (5) and Methanobacteriales (3); genera UBA71 (3), Methanomethylophilus (1), MX-02 (1), and Methanobrevibacter (3). We recovered the first US swine Methanobrevibacter UBA71 sp006954425 and Methanobrevibacter gottschalkii MAGs. The Methanobacteriales MAGs were identified primarily during the young, preweaned host whereas Methanomassiliicoccales primarily in the adult host. Moreover, we identified our methanogens in metagenomic sequences from Chinese swine, US adult humans, Mexican adult humans, Swedish adult humans, and paleontological humans, indicating that methanogens span different hosts, geography and time. We determined complete metabolic pathways for all three methanogenic pathways: hydrogenotrophic, methylotrophic, and acetoclastic. This study provided the first evidence of acetoclastic methanogenesis in archaea of monogastric hosts which indicated a previously unknown capability for acetate utilization in methanogenesis for monogastric methanogens. Overall, we hypothesized that the age-associated detection patterns were due to differential substrate availability via the host diet and microbial metabolism, and that these methanogenic functions are likely crucial to methanogens across hosts. This study provided a comprehensive, genome-centric investigation of monogastric-associated methanogens which will further improve our understanding of microbiome development and functions.
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Affiliation(s)
- Brandi Feehan
- Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Qinghong Ran
- Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Victoria Dorman
- Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Kourtney Rumback
- Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Sophia Pogranichniy
- Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Kaitlyn Ward
- Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Robert Goodband
- Department of Animal Sciences and Industry, College of Agriculture, Kansas State University, Manhattan, KS, 66506, USA
| | | | - Sonny T M Lee
- Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, KS, 66506, USA.
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Liu J, Zhou S, Wang Y, Liu J, Sun S, Sun Y, Xu P, Xu X, Zhu B, Wu H. ZeXieYin Formula alleviates TMAO-induced cognitive impairment by restoring synaptic plasticity damage. JOURNAL OF ETHNOPHARMACOLOGY 2023; 314:116604. [PMID: 37178985 DOI: 10.1016/j.jep.2023.116604] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 04/29/2023] [Accepted: 05/03/2023] [Indexed: 05/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Treating cognitive impairment is a challenging and necessary research topic. ZeXieYin Formula (ZXYF), is a traditional herbal formula documented in the book of HuangDiNeiJing. Our previous studies demonstrated the ameliorative effects of ZXYF on atherosclerosis by reducing the plasma trimethylamine oxide (TMAO) level. TMAO is a metabolite of gut microorganisms, our recent research found that the increasing level of TMAO may have adverse effects on cognitive functions. AIM OF THE STUDY Our study mainly focused on the therapeutic effects of ZXYF on TMAO-induced cognitive impairment in mice and explored its underlying mechanism. MATERIALS AND METHODS After the TMAO-induced cognitive impairment mice models were established, we applied behavioral tests to estimate the learning and memory ability of the ZXYF intervention mice. Liquid chromatography-mass spectrometry (LC-MS) was used to quantify the TMAO levels in plasma and the brain. The effects of ZXYF on the hippocampal synaptic structure and the neurons were observed by transmission electron microscopy (TEM) and Nissl staining. In addition, western-blotting (WB) and immunohistochemical (IHC) staining were used to detect the level of related proteins in the synaptic structure and further verify the changes in synaptic plasticity and the mTOR pathway after ZXYF administration. RESULTS Behavioral tests showed that the learning and memory ability of mice impaired after a period of TMAO intervention and ZXYF could alleviate these changes. A series of results showed that ZXYF partly restored the damage of hippocampal synapse and neurons in TMAO-induced mice, at the same time, the expression of synapse-related proteins and mTOR pathway-related proteins were significantly regulated compared with the damage caused by TMAO. CONCLUSION ZXYF could alleviate TMAO-induced cognitive impairment by improving synaptic function, reducing neuronal damage, regulating synapse-associated proteins, and regulating the mTOR signaling pathway.
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Affiliation(s)
- Jing Liu
- College of Traditional Chinese Medicine and College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China
| | - Shihan Zhou
- College of Traditional Chinese Medicine and College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China
| | - Yanqing Wang
- College of Traditional Chinese Medicine and College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China
| | - Jinling Liu
- College of Traditional Chinese Medicine and College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China
| | - SuPing Sun
- College of Traditional Chinese Medicine and College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China
| | - Yan Sun
- College of Traditional Chinese Medicine and College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China
| | - Ping Xu
- College of Traditional Chinese Medicine and College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China
| | - Xu Xu
- Nantong TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Nantong, Jiangsu, 226001, China
| | - Boran Zhu
- College of Traditional Chinese Medicine and College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China.
| | - Haoxin Wu
- College of Traditional Chinese Medicine and College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China; Key Laboratory of Integrative Biomedicine for Brain Diseases, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210046, China.
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Shanmugham M, Bellanger S, Leo CH. Gut-Derived Metabolite, Trimethylamine-N-oxide (TMAO) in Cardio-Metabolic Diseases: Detection, Mechanism, and Potential Therapeutics. Pharmaceuticals (Basel) 2023; 16:ph16040504. [PMID: 37111261 PMCID: PMC10142468 DOI: 10.3390/ph16040504] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 03/17/2023] [Accepted: 03/23/2023] [Indexed: 03/30/2023] Open
Abstract
Trimethylamine N-oxide (TMAO) is a biologically active gut microbiome-derived dietary metabolite. Recent studies have shown that high circulating plasma TMAO levels are closely associated with diseases such as atherosclerosis and hypertension, and metabolic disorders such as diabetes and hyperlipidemia, contributing to endothelial dysfunction. There is a growing interest to understand the mechanisms underlying TMAO-induced endothelial dysfunction in cardio-metabolic diseases. Endothelial dysfunction mediated by TMAO is mainly driven by inflammation and oxidative stress, which includes: (1) activation of foam cells; (2) upregulation of cytokines and adhesion molecules; (3) increased production of reactive oxygen species (ROS); (4) platelet hyperreactivity; and (5) reduced vascular tone. In this review, we summarize the potential roles of TMAO in inducing endothelial dysfunction and the mechanisms leading to the pathogenesis and progression of associated disease conditions. We also discuss the potential therapeutic strategies for the treatment of TMAO-induced endothelial dysfunction in cardio-metabolic diseases.
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Affiliation(s)
- Meyammai Shanmugham
- Science, Math & Technology, Singapore University of Technology & Design, 8 Somapah Road, Singapore 487372, Singapore
| | - Sophie Bellanger
- A*STAR Skin Research Labs, Agency for Science, Technology and Research, Singapore 138648, Singapore
| | - Chen Huei Leo
- Science, Math & Technology, Singapore University of Technology & Design, 8 Somapah Road, Singapore 487372, Singapore
- Correspondence: ; Tel.: +65-6434-8213
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Song D, Wang X, Ma Y, Liu NN, Wang H. Beneficial insights into postbiotics against colorectal cancer. Front Nutr 2023; 10:1111872. [PMID: 36969804 PMCID: PMC10036377 DOI: 10.3389/fnut.2023.1111872] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/21/2023] [Indexed: 03/12/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent and life-threatening cancer types with limited therapeutic options worldwide. Gut microbiota has been recognized as the pivotal determinant in maintaining gastrointestinal (GI) tract homeostasis, while dysbiosis of gut microbiota contributes to CRC development. Recently, the beneficial role of postbiotics, a new concept in describing microorganism derived substances, in CRC has been uncovered by various studies. However, a comprehensive characterization of the molecular identity, mechanism of action, or routes of administration of postbiotics, particularly their role in CRC, is still lacking. In this review, we outline the current state of research toward the beneficial effects of gut microbiota derived postbiotics against CRC, which will represent the key elements of future precision-medicine approaches in the development of novel therapeutic strategies targeting gut microbiota to improve treatment outcomes in CRC.
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Affiliation(s)
| | | | | | - Ning-Ning Liu
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hui Wang
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Ramírez GA, Bar-Shalom R, Furlan A, Romeo R, Gavagnin M, Calabrese G, Garber AI, Steindler L. Bacterial aerobic methane cycling by the marine sponge-associated microbiome. MICROBIOME 2023; 11:49. [PMID: 36899421 PMCID: PMC9999580 DOI: 10.1186/s40168-023-01467-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 01/13/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Methanotrophy by the sponge-hosted microbiome has been mainly reported in the ecological context of deep-sea hydrocarbon seep niches where methane is either produced geothermically or via anaerobic methanogenic archaea inhabiting the sulfate-depleted sediments. However, methane-oxidizing bacteria from the candidate phylum Binatota have recently been described and shown to be present in oxic shallow-water marine sponges, where sources of methane remain undescribed. RESULTS Here, using an integrative -omics approach, we provide evidence for sponge-hosted bacterial methane synthesis occurring in fully oxygenated shallow-water habitats. Specifically, we suggest methane generation occurs via at least two independent pathways involving methylamine and methylphosphonate transformations that, concomitantly to aerobic methane production, generate bioavailable nitrogen and phosphate, respectively. Methylphosphonate may be sourced from seawater continuously filtered by the sponge host. Methylamines may also be externally sourced or, alternatively, generated by a multi-step metabolic process where carnitine, derived from sponge cell debris, is transformed to methylamine by different sponge-hosted microbial lineages. Finally, methanotrophs specialized in pigment production, affiliated to the phylum Binatota, may provide a photoprotective function, closing a previously undescribed C1-metabolic loop that involves both the sponge host and specific members of the associated microbial community. CONCLUSION Given the global distribution of this ancient animal lineage and their remarkable water filtration activity, sponge-hosted methane cycling may affect methane supersaturation in oxic coastal environments. Depending on the net balance between methane production and consumption, sponges may serve as marine sources or sinks of this potent greenhouse gas. Video Abstract.
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Affiliation(s)
- Gustavo A Ramírez
- Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, 199 Aba Khoushy Ave., Mount Carmel, Haifa, Israel
- Present address: Department of Biological Sciences, California State University, Los Angeles, CA, USA
| | - Rinat Bar-Shalom
- Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, 199 Aba Khoushy Ave., Mount Carmel, Haifa, Israel
| | - Andrea Furlan
- Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, 199 Aba Khoushy Ave., Mount Carmel, Haifa, Israel
| | - Roberto Romeo
- Istituto Nazionale di Oceanografia e di Geofisica Sperimentale, Trieste, Italy
| | - Michelle Gavagnin
- Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, 199 Aba Khoushy Ave., Mount Carmel, Haifa, Israel
| | - Gianluca Calabrese
- Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, 199 Aba Khoushy Ave., Mount Carmel, Haifa, Israel
| | - Arkadiy I Garber
- School of Life Science, Arizona State University, Tempe, AZ, USA
| | - Laura Steindler
- Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, 199 Aba Khoushy Ave., Mount Carmel, Haifa, Israel.
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Improved Quantitative Real-Time PCR Protocol for Detection and Quantification of Methanogenic Archaea in Stool Samples. Microorganisms 2023; 11:microorganisms11030660. [PMID: 36985233 PMCID: PMC10051802 DOI: 10.3390/microorganisms11030660] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/24/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Methanogenic archaea are an important component of the human and animal intestinal microbiota, and yet their presence is rarely reported in publications describing the subject. One of the methods of quantifying the prevalence of methanogens is quantitative real-time PCR (qPCR) of the methanogen-specific mcrA gene, and one of the possible reasons for detection failure is usually a methodology bias. Here, we refined the existing protocol by changing one of the primers and improving the conditions of the qPCR reaction. As a result, at the expense of a slightly lower yet acceptable PCR efficiency, the new assay was characterized by increased specificity and sensitivity and a wider linear detection range of 7 orders of magnitude. The lowest copy number of mcrA quantified at a frequency of 100% was 21 copies per reaction. The other validation parameters tested, such as reproducibility and linearity, also gave satisfactory results. Overall, we were able to minimize the negative impacts of primer dimerization and other cross-reactions on qPCR and increase the number of not only detectable but also quantifiable stool samples—or in this case, chicken droppings.
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Zhang L, Yu F, Xia J. Trimethylamine N-oxide: role in cell senescence and age-related diseases. Eur J Nutr 2023; 62:525-541. [PMID: 36219234 DOI: 10.1007/s00394-022-03011-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 09/21/2022] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Hayflick and Moorhead first demonstrated cell senescence as the irreversible growth arrest of cells after prolonged cultivation. Telomere shortening and oxidative stress are the fundamental mechanisms that drive cell senescence. Increasing studies have shown that TMAO is closely associated with cellular aging and age-related diseases. An emerging body of evidence from animal models, especially mice, has identified that TMAO contributes to senescence from multiple pathways and appears to accelerate many neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. However, the specific mechanism of how TMAO speeds aging is still not completely clear. MATERIAL AND METHODS In this review, we summarize some key findings in TMAO, cell senescence, and age-related diseases. We focused particular attention on the potential mechanisms for clinical transformation to find ways to interfere with the aging process. CONCLUSION TMAO can accelerate cell senescence by causing mitochondrial damage, superoxide formation, and promoting the generation of pro-inflammatory factors.
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Affiliation(s)
- Lin Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.,Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
| | - Fang Yu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China
| | - Jian Xia
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China. .,Clinical Research Center for Cerebrovascular Disease of Hunan Province, Central South University, Changsha, Hunan, China. .,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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Constantino-Jonapa LA, Espinoza-Palacios Y, Escalona-Montaño AR, Hernández-Ruiz P, Amezcua-Guerra LM, Amedei A, Aguirre-García MM. Contribution of Trimethylamine N-Oxide (TMAO) to Chronic Inflammatory and Degenerative Diseases. Biomedicines 2023; 11:431. [PMID: 36830968 PMCID: PMC9952918 DOI: 10.3390/biomedicines11020431] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/23/2023] [Accepted: 01/27/2023] [Indexed: 02/05/2023] Open
Abstract
Trimethylamine N-oxide (TMAO) is a metabolite produced by the gut microbiota and has been mainly associated with an increased incidence of cardiovascular diseases (CVDs) in humans. There are factors that affect one's TMAO level, such as diet, drugs, age, and hormones, among others. Gut dysbiosis in the host has been studied recently as a new approach to understanding chronic inflammatory and degenerative diseases, including cardiovascular diseases, metabolic diseases, and Alzheimer's disease. These disease types as well as COVID-19 are known to modulate host immunity. Diabetic and obese patients have been observed to have an increase in their level of TMAO, which has a direct correlation with CVDs. This metabolite is attributed to enhancing the inflammatory pathways through cholesterol and bile acid dysregulation, promoting foam cell formation. Additionally, TMAO activates the transcription factor NF-κB, which, in turn, triggers cytokine production. The result can be an exaggerated inflammatory response capable of inducing endoplasmic reticulum stress, which is responsible for various diseases. Due to the deleterious effects that this metabolite causes in its host, it is important to search for new therapeutic agents that allow a reduction in the TMAO levels of patients and that, thus, allow patients to be able to avoid a severe cardiovascular event. The present review discussed the synthesis of TMAO and its contribution to the pathogenesis of various inflammatory diseases.
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Affiliation(s)
- Luis A. Constantino-Jonapa
- Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, UNAM, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico
| | - Yoshua Espinoza-Palacios
- Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, UNAM, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico
| | - Alma R. Escalona-Montaño
- Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, UNAM, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico
| | - Paulina Hernández-Ruiz
- Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, UNAM, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico
| | - Luis M. Amezcua-Guerra
- Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
- Interdisciplinary Internal Medicine Unit, Careggi University Hospital, 50134 Florence, Italy
| | - María M. Aguirre-García
- Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, UNAM, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México 14080, Mexico
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Dai Q, Ding J, Cui X, Zhu Y, Chen H, Zhu L. Beyond bacteria: Reconstructing microorganism connections and deciphering the predicted mutualisms in mammalian gut metagenomes. Ecol Evol 2023; 13:e9829. [PMID: 36844675 PMCID: PMC9944162 DOI: 10.1002/ece3.9829] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 01/24/2023] [Accepted: 01/30/2023] [Indexed: 02/24/2023] Open
Abstract
Numerous gut microbial studies have focused on bacteria. However, archaea, viruses, fungi, protists, and nematodes are also regular residents of the gut ecosystem. Little is known about the composition and potential interactions among these six kingdoms in the same samples. Here, we unraveled the complex connection among them using approximately 123 gut metagenomes from 42 mammalian species (including carnivores, omnivores, and herbivores). We observed high variation in bacterial and fungal families and relatively low variation in archaea, viruses, protists, and nematodes. We found that some fungi in the mammalian intestine might come from environmental sources (e.g., soil and dietary plants), and some might be native to the intestine (e.g., the occurrence of Neocallimastigomycetes). The Methanobacteriaceae and Plasmodiidae families (archaea and protozoa, respectively) were predominant in these metagenomes, whereas Onchocercidae and Trichuridae were the two most common nematodes, and Siphoviridae and Myoviridae the two most common virus families in these mammalian gut metagenomes. Interestingly, most of the pairwise co-occurrence patterns were significantly positive among these six kingdoms, and significantly negative networks mainly occurred between fungi and prokaryotes (both bacteria and archaea). Our study revealed some inconvenient characteristics in the mammalian gut microorganism ecosystem: (1) the community formed by members of the analyzed kingdoms reflects the life history of the host and the potential threat posed by pathogenic protists and nematodes in mammals; and (2) the networks suggest the existence of predicted mutualism among members of these six kingdoms and of the predicted competition, mainly among fungi and other kingdoms.
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Affiliation(s)
- Qinlong Dai
- Sichuan Liziping National Natural ReserveShimianChina
| | | | - Xinyuan Cui
- College of Life ScienceNanjing Normal UniversityNanjingChina
| | - Yudong Zhu
- Sichuan Liziping National Natural ReserveShimianChina
| | - Hua Chen
- Mingke Biotechnology (Hangzhou) Co., Ltd.HangzhouChina
| | - Lifeng Zhu
- College of PharmacyNanjing University of Chinese MedicineNanjingChina
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Li J, Kang PT, Jiang R, Lee JY, Soares JA, Krzycki JA, Chan MK. Insights into pyrrolysine function from structures of a trimethylamine methyltransferase and its corrinoid protein complex. Commun Biol 2023; 6:54. [PMID: 36646841 PMCID: PMC9842639 DOI: 10.1038/s42003-022-04397-3] [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: 05/02/2022] [Accepted: 12/21/2022] [Indexed: 01/18/2023] Open
Abstract
The 22nd genetically encoded amino acid, pyrrolysine, plays a unique role in the key step in the growth of methanogens on mono-, di-, and tri-methylamines by activating the methyl group of these substrates for transfer to a corrinoid cofactor. Previous crystal structures of the Methanosarcina barkeri monomethylamine methyltransferase elucidated the structure of pyrrolysine and provide insight into its role in monomethylamine activation. Herein, we report the second structure of a pyrrolysine-containing protein, the M. barkeri trimethylamine methyltransferase MttB, and its structure bound to sulfite, a substrate analog of trimethylamine. We also report the structure of MttB in complex with its cognate corrinoid protein MttC, which specifically receives the methyl group from the pyrrolysine-activated trimethylamine substrate during methanogenesis. Together these structures provide key insights into the role of pyrrolysine in methyl group transfer from trimethylamine to the corrinoid cofactor in MttC.
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Affiliation(s)
- Jiaxin Li
- grid.10784.3a0000 0004 1937 0482School of Life Sciences, and Center of Novel Biomaterials, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Patrick T. Kang
- grid.261103.70000 0004 0459 7529Department of Integrative Medical Sciences, College of Medicine, Northeast Ohio Medical University, Rootstown, OH 44272 USA ,grid.261331.40000 0001 2285 7943Ohio State University Biochemistry Program, Columbus, OH 43210 USA
| | - Ruisheng Jiang
- grid.261331.40000 0001 2285 7943Department of Microbiology, The Ohio State University, Columbus, OH 43210 USA
| | - Jodie Y. Lee
- grid.261331.40000 0001 2285 7943Department of Microbiology, The Ohio State University, Columbus, OH 43210 USA ,grid.422834.b0000 0004 0387 4571TechLab, Inc., Blacksburg, VA 24060 USA
| | - Jitesh A. Soares
- grid.261331.40000 0001 2285 7943Department of Microbiology, The Ohio State University, Columbus, OH 43210 USA ,grid.286879.a0000 0001 1090 0879Division of Scientific Advancement, American Chemical Society, Washington, DC 20036 USA
| | - Joseph A. Krzycki
- grid.261331.40000 0001 2285 7943Ohio State University Biochemistry Program, Columbus, OH 43210 USA ,grid.261331.40000 0001 2285 7943Department of Microbiology, The Ohio State University, Columbus, OH 43210 USA
| | - Michael K. Chan
- grid.10784.3a0000 0004 1937 0482School of Life Sciences, and Center of Novel Biomaterials, The Chinese University of Hong Kong, Shatin, Hong Kong, China ,grid.261331.40000 0001 2285 7943Ohio State University Biochemistry Program, Columbus, OH 43210 USA
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Liu X, He G, Lan Y, Guo W, Liu X, Li J, Liu A, He M, Liu X, Fan Z, Zhang Y. Virome and metagenomic analysis reveal the distinct distribution of microbiota in human fetal gut during gestation. Front Immunol 2023; 13:1079294. [PMID: 36685560 PMCID: PMC9850102 DOI: 10.3389/fimmu.2022.1079294] [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: 10/25/2022] [Accepted: 12/14/2022] [Indexed: 01/07/2023] Open
Abstract
Studies have shown that fetal immune cell activation may result from potential exposure to microbes, although the presence of microbes in fetus has been a controversial topic. Here, we combined metagenomic and virome techniques to investigate the presence of bacteria and viruses in fetal tissues (small intestine, cecum, and rectum). We found that the fetal gut is not a sterile environment and has a low abundance but metabolically rich microbiome. Specifically, Proteobacteria and Actinobacteria were the dominant bacteria phyla of fetal gut. In total, 700 species viruses were detected, and Human betaherpesvirus 5 was the most abundant eukaryotic viruses. Especially, we first identified Methanobrevibacter smithii in fetal gut. Through the comparison with adults' gut microbiota we found that Firmicutes and Bacteroidetes gradually became the main force of gut microbiota during the process of growth and development. Interestingly, 6 antibiotic resistance genes were shared by the fetus and adults. Our results indicate the presence of microbes in the fetal gut and demonstrate the diversity of bacteria, archaea and viruses, which provide support for the studies related to early fetal immunity. This study further explores the specific composition of viruses in the fetal gut and the similarities between fetal and adults' gut microbiota, which is valuable for understanding human fetal immunity development during gestation.
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Affiliation(s)
- Xu Liu
- Key Laboratory of Bioresources and Ecoenvironment, Ministry of Education, College of Life Sciences, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China,Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, China
| | - Guolin He
- Key Laboratory of Bioresources and Ecoenvironment, Ministry of Education, College of Life Sciences, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China,Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Yue Lan
- Key Laboratory of Bioresources and Ecoenvironment, Ministry of Education, College of Life Sciences, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Weijie Guo
- Key Laboratory of Bioresources and Ecoenvironment, Ministry of Education, College of Life Sciences, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Xuyuan Liu
- Key Laboratory of Bioresources and Ecoenvironment, Ministry of Education, College of Life Sciences, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Jing Li
- Key Laboratory of Bioresources and Ecoenvironment, Ministry of Education, College of Life Sciences, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Anqing Liu
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China
| | - Miao He
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China
| | - Xinhui Liu
- Key Laboratory of Bioresources and Ecoenvironment, Ministry of Education, College of Life Sciences, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China,Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Zhenxin Fan
- Key Laboratory of Bioresources and Ecoenvironment, Ministry of Education, College of Life Sciences, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China,Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, China,*Correspondence: Yaoyao Zhang, ; Zhenxin Fan,
| | - Yaoyao Zhang
- Key Laboratory of Bioresources and Ecoenvironment, Ministry of Education, College of Life Sciences, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China,Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China,*Correspondence: Yaoyao Zhang, ; Zhenxin Fan,
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Koning M, Herrema H, Nieuwdorp M, Meijnikman AS. Targeting nonalcoholic fatty liver disease via gut microbiome-centered therapies. Gut Microbes 2023; 15:2226922. [PMID: 37610978 PMCID: PMC10305510 DOI: 10.1080/19490976.2023.2226922] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 06/13/2023] [Accepted: 06/14/2023] [Indexed: 08/25/2023] Open
Abstract
Humans possess abundant amounts of microorganisms, including bacteria, fungi, viruses, and archaea, in their gut. Patients with nonalcoholic fatty liver disease (NAFLD) exhibit alterations in their gut microbiome and an impaired gut barrier function. Preclinical studies emphasize the significance of the gut microbiome in the pathogenesis of NAFLD. In this overview, we explore how adjusting the gut microbiome could serve as an innovative therapeutic strategy for NAFLD. We provide a summary of current information on untargeted techniques such as probiotics and fecal microbiota transplantation, as well as targeted microbiome-focused therapies including engineered bacteria, prebiotics, postbiotics, and phages for the treatment of NAFLD.
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Affiliation(s)
- Mijra Koning
- Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences Diabetes, Amsterdam, The Netherlands
| | - Hilde Herrema
- Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands
- Amsterdam Gastroenterology and Metabolism, Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences Diabetes, Amsterdam, The Netherlands
| | - Abraham S. Meijnikman
- Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences Diabetes, Amsterdam, The Netherlands
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Hoegenauer C, Hammer HF, Mahnert A, Moissl-Eichinger C. Methanogenic archaea in the human gastrointestinal tract. Nat Rev Gastroenterol Hepatol 2022; 19:805-813. [PMID: 36050385 DOI: 10.1038/s41575-022-00673-z] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/26/2022] [Indexed: 12/24/2022]
Abstract
The human microbiome is strongly interwoven with human health and disease. Besides bacteria, viruses and eukaryotes, numerous archaea are located in the human gastrointestinal tract and are responsible for methane production, which can be measured in clinical methane breath analyses. Methane is an important readout for various diseases, including intestinal methanogen overgrowth. Notably, the archaea responsible for methane production are largely overlooked in human microbiome studies due to their non-bacterial biology and resulting detection issues. As such, their importance for health and disease remains largely unclear to date, in particular as not a single archaeal representative has been deemed to be pathogenic. In this Perspective, we discuss the current knowledge on the clinical relevance of methanogenic archaea. We explain the archaeal unique response to antibiotics and their negative and positive effects on human physiology, and present the current understanding of the use of methane as a diagnostic marker.
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Affiliation(s)
- Christoph Hoegenauer
- Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Heinz F Hammer
- Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Alexander Mahnert
- Diagnostic and Research Department of Microbiology, Hygiene and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Christine Moissl-Eichinger
- Diagnostic and Research Department of Microbiology, Hygiene and Environmental Medicine, Medical University of Graz, Graz, Austria.
- BioTechMed Graz, Graz, Austria.
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Li X, Song J, Shi X, Huang M, Liu L, Yi G, Yang N, Xu G, Zheng J. FMO3 deficiency of duck leads to decreased lipid deposition and increased antibacterial activity. J Anim Sci Biotechnol 2022; 13:119. [DOI: 10.1186/s40104-022-00777-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 09/06/2022] [Indexed: 11/17/2022] Open
Abstract
Abstract
Background
Most duck eggs possess a fishy odor, indicating that ducks generally exhibit impaired trimethylamine (TMA) metabolism. TMA accumulation is responsible for this unpleasant odor, and TMA metabolism plays an essential role in trimethylaminuria (TMAU), also known as fish odor syndrome. In this study, we focused on the unusual TMA metabolism mechanism in ducks, and further explored the unclear reasons leading to the debilitating TMA metabolism.
Methods
To achieve this, transcriptome, proteome, and metagenome analyses were first integrated based on the constructed duck populations with high and low TMA metabolism abilities. Additionally, further experiments were conducted to validate the hypothesis regarding the limited flavin-containing monooxygenase 3 (FMO3) metabolism ability of ducks.
Results
The study demonstrated that liver FMO3 and cecal microbes, including Akkermansia and Mucispirillum, participated in TMA metabolism in ducks. The limited oxidation ability of FMO3 explains the weakening of TMA metabolism in ducks. Nevertheless, it decreases lipid deposition and increases antibacterial activity, contributing to its survival and reproduction during the evolutionary adaptation process.
Conclusions
This study demonstrated the function of FMO3 and intestinal microbes in regulating TMA metabolism and illustrated the biological significance of FMO3 impairment in ducks.
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42
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Li P, Wang H, Guo L, Gou X, Chen G, Lin D, Fan D, Guo X, Liu Z. Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study. BMC Med 2022; 20:443. [PMID: 36380372 PMCID: PMC9667679 DOI: 10.1186/s12916-022-02657-x] [Citation(s) in RCA: 271] [Impact Index Per Article: 90.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 11/08/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on preeclampsia-eclampsia is unknown. METHODS A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis (n=13,266) conducted by the MiBioGen consortium. The summary statistics of preeclampsia-eclampsia were obtained from the FinnGen consortium R7 release data (5731 cases and 160,670 controls). Inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted model, MR-PRESSO, and cML-MA were used to examine the causal association between gut microbiota and preeclampsia-eclampsia. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be causally associated with preeclampsia-eclampsia in forward Mendelian randomization analysis. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. RESULTS Inverse variance weighted estimates suggested that Bifidobacterium had a protective effect on preeclampsia-eclampsia (odds ratio = 0.76, 95% confidence interval: 0.64-0.89, P = 8.03 × 10-4). In addition, Collinsella (odds ratio = 0.77, 95% confidence interval: 0.60-0.98, P = 0.03), Enterorhabdus (odds ratio = 0.76, 95% confidence interval: 0.62-0.93, P = 8.76 × 10-3), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63-0.91, P = 2.43 × 10-3), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65-0.92, P = 3.77 × 10-3), and Tyzzerella 3 (odds ratio = 0.85, 95% confidence interval: 0.74-0.97, P = 0.01) presented a suggestive association with preeclampsia-eclampsia. According to the results of reverse MR analysis, no significant causal effect of preeclampsia-eclampsia was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. CONCLUSIONS This two-sample Mendelian randomization study found that Bifidobacterium was causally associated with preeclampsia-eclampsia. Further randomized controlled trials are needed to clarify the protective effect of probiotics on preeclampsia-eclampsia and their specific protective mechanisms.
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Affiliation(s)
- Pengsheng Li
- Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China.,Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi, Foshan, 528000, Guangdong, China
| | - Haiyan Wang
- Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China.,Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi, Foshan, 528000, Guangdong, China.,Biobank, Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China
| | - Lan Guo
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Xiaoyan Gou
- Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China.,Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi, Foshan, 528000, Guangdong, China.,Biobank, Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China
| | - Gengdong Chen
- Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China.,Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi, Foshan, 528000, Guangdong, China
| | - Dongxin Lin
- Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China.,Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi, Foshan, 528000, Guangdong, China
| | - Dazhi Fan
- Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China.,Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi, Foshan, 528000, Guangdong, China
| | - Xiaoling Guo
- Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi, Foshan, 528000, Guangdong, China
| | - Zhengping Liu
- Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China. .,Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi, Foshan, 528000, Guangdong, China.
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Mudimela S, Vishwanath NK, Pillai A, Morales R, Marrelli SP, Barichello T, Giridharan VV. Clinical significance and potential role of trimethylamine N-oxide in neurological and neuropsychiatric disorders. Drug Discov Today 2022; 27:103334. [PMID: 35998800 PMCID: PMC10392962 DOI: 10.1016/j.drudis.2022.08.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 04/18/2022] [Accepted: 08/09/2022] [Indexed: 11/23/2022]
Abstract
In the past three decades, research on the gut microbiome and its metabolites, such as trimethylamines (TMA), trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), bile acids, tryptophan and indole derivatives, has attracted the attention of many scientists and industrialists. Among these metabolites, TMAO is produced from dietary choline, phosphatidylcholine, carnitine,andbetaine. TMAO and other gut metabolites, such as TMA and SCFAs, reach the brain by crossing the blood-brain barrier (BBB) and are involved in brain development, neurogenesis, and behavior. Gut-microbiota composition is influenced by diet, lifestyle, antibiotics, and age. Several studies have confirmed that altered TMAO levels contribute to metabolic, vascular, psychiatric, and neurodegenerative disorders. This review focuses on how altered TMAO levels impact oxidative stress, microglial activation, and the apoptosis of neurons, and may lead to neuroinflammation, which can subsequently result in the development of psychiatric, cognitive, and behavioral disorders.
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Affiliation(s)
- Sowjanya Mudimela
- Faculty of Pharmaceutical Sciences, PES University, HN-Campus, Bengaluru, Karnataka, India
| | | | - Anilkumar Pillai
- Pathophysiology of Neuropsychiatric Disorders Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center at Houston (UTHealth), Houston, TX, USA; Research and Development, Charlie Norwood VA Medical Center, Augusta, GA, USA; Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Rodrigo Morales
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Centro Integrativo de Biologia y Quimica Aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago, Chile
| | - Sean P Marrelli
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Tatiana Barichello
- Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center at Houston (UTHealth), Houston, TX, USA; Faillace Department of Psychiatry and Behavioral Sciences, Translational Psychiatry Program, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Experimental Physiopathology Laboratory, Graduate Program in Health Sciences, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Vijayasree V Giridharan
- Faillace Department of Psychiatry and Behavioral Sciences, Translational Psychiatry Program, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
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Francisco AJ. Helicobacter Pylori Infection Induces Intestinal Dysbiosis That Could Be Related to the Onset of Atherosclerosis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:9943158. [PMID: 36317116 PMCID: PMC9617700 DOI: 10.1155/2022/9943158] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 10/05/2022] [Accepted: 10/06/2022] [Indexed: 11/17/2022]
Abstract
Cardiovascular diseases represent one of the first causes of death around the world, and atherosclerosis is one of the first steps in the development of them. Although these problems occur mainly in elderly, the incidence in younger people is being reported, and an undetermined portion of patients without the classic risk factors develop subclinical atherosclerosis at earlier stages of life. Recently, both the H. pylori infection and the intestinal microbiota have been linked to atherosclerosis. The mechanisms behind those associations are poorly understood, but some of the proposed explanations are (a) the effect of the chronic systemic inflammation induced by H. pylori, (b) a direct action over the endothelial cells by the cytotoxin associated gene A protein, and (c) alterations of the lipid metabolism and endothelial dysfunction induced by H. pylori infection. Regarding the microbiota, several studies show that induction of atherosclerosis is related to high levels of Trimethylamine N-oxide. In this review, we present the information published about the effects of H. pylori over the intestinal microbiota and their relationship with atherosclerosis and propose a hypothesis to explain the nature of these associations. If H. pylori contributes to atherosclerosis, then interventions for eradication and restoration of the gut microbiota at early stages could represent a way to prevent disease progression.
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Affiliation(s)
- Avilés-Jiménez Francisco
- Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Pediatría. Centro Médico Nacional Siglo XXI. IMSS, Ciudad de México, Mexico
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Sun C, Wang Z, Hu L, Zhang X, Chen J, Yu Z, Liu L, Wu M. Targets of statins intervention in LDL-C metabolism: Gut microbiota. Front Cardiovasc Med 2022; 9:972603. [PMID: 36158845 PMCID: PMC9492915 DOI: 10.3389/fcvm.2022.972603] [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: 06/18/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
Increasing researches have considered gut microbiota as a new “metabolic organ,” which mediates the occurrence and development of metabolic diseases. In addition, the liver is an important organ of lipid metabolism, and abnormal lipid metabolism can cause the elevation of blood lipids. Among them, elevated low-density lipoprotein cholesterol (LDL-C) is related with ectopic lipid deposition and metabolic diseases, and statins are widely used to lower LDL-C. In recent years, the gut microbiota has been shown to mediate statins efficacy, both in animals and humans. The effect of statins on microbiota abundance has been deeply explored, and the pathways through which statins reduce the LDL-C levels by affecting the abundance of microbiota have gradually been explored. In this review, we discussed the interaction between gut microbiota and cholesterol metabolism, especially the cholesterol-lowering effect of statins mediated by gut microbiota, via AMPK-PPARγ-SREBP1C/2, FXR and PXR-related, and LPS-TLR4-Myd88 pathways, which may help to explain the individual differences in statins efficacy.
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Affiliation(s)
- ChangXin Sun
- Beijing University of Chinese Medicine, Beijing, China
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - ZePing Wang
- Beijing University of Chinese Medicine, Beijing, China
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - LanQing Hu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - XiaoNan Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - JiYe Chen
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - ZongLiang Yu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - LongTao Liu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: LongTao Liu
| | - Min Wu
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Min Wu
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Mafra D, Ribeiro M, Fonseca L, Regis B, Cardozo LFMF, Fragoso Dos Santos H, Emiliano de Jesus H, Schultz J, Shiels PG, Stenvinkel P, Rosado A. Archaea from the gut microbiota of humans: Could be linked to chronic diseases? Anaerobe 2022; 77:102629. [PMID: 35985606 DOI: 10.1016/j.anaerobe.2022.102629] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 07/31/2022] [Accepted: 08/11/2022] [Indexed: 11/01/2022]
Abstract
Archaea comprise a unique domain of organisms with distinct biochemical and genetic differences from bacteria. Methane-forming archaea, methanogens, constitute the predominant group of archaea in the human gut microbiota, with Methanobrevibacter smithii being the most prevalent. However, the effect of methanogenic archaea and their methane production on chronic disease remains controversial. As perturbation of the microbiota is a feature of chronic conditions, such as cardiovascular disease, neurodegenerative diseases and chronic kidney disease, assessing the influence of archaea could provide a new clue to mitigating adverse effects associated with dysbiosis. In this review, we will discuss the putative role of archaea in the gut microbiota in humans and the possible link to chronic diseases.
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Affiliation(s)
- Denise Mafra
- Graduate Program in Biological Sciences - Physiology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, (RJ), Brazil; Graduate Program in Nutrition Sciences, Fluminense Federal University (UFF), Niterói, Brazil; Graduate Program in Medical Sciences, Fluminense Federal University (UFF), Niterói, Brazil.
| | - Marcia Ribeiro
- Graduate Program in Nutrition Sciences, Fluminense Federal University (UFF), Niterói, Brazil
| | - Larissa Fonseca
- Graduate Program in Medical Sciences, Fluminense Federal University (UFF), Niterói, Brazil
| | - Bruna Regis
- Graduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Brazil
| | - Ludmila F M F Cardozo
- Graduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Brazil
| | | | | | - Junia Schultz
- Microbial Ecogenomics and Biotechnology Laboratory, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Makkah, 23955, Saudi Arabia
| | - Paul G Shiels
- Wolfson Wohl Translational Research Centre, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1QH, UK
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Stockholm, Sweden
| | - Alexandre Rosado
- Microbial Ecogenomics and Biotechnology Laboratory, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Makkah, 23955, Saudi Arabia
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Abstract
Trillions of microorganisms, including bacteria, archaea, fungi, and viruses, live in or on the human body. Microbe-microbe and microbe-host interactions are often influenced by diffusible and microbe-associated small molecules. Over the past few years, it has become evident that these interactions have a substantial impact on human health and disease. In this Perspective, we summarize the research involving the discovery of methanogenic and non-methanogenic archaea associated with the human body. In particular, we emphasize the importance of some archaeal metabolites in mediating intra- and interspecies interactions in the ecological environment of the human body. A deep understanding of the archaeal metabolites as well as their biological functions may reveal in more detail whether and how archaea are involved in maintaining human health and/or causing certain diseases.
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Affiliation(s)
- Mingwei Cai
- Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China
| | - Xiaoyu Tang
- Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China
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Xiong X, Rao Y, Tu X, Wang Z, Gong J, Yang Y, Wu H, Liu X. Gut archaea associated with bacteria colonization and succession during piglet weaning transitions. BMC Vet Res 2022; 18:243. [PMID: 35751084 PMCID: PMC9229118 DOI: 10.1186/s12917-022-03330-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 05/27/2022] [Indexed: 11/10/2022] Open
Abstract
Background Host-associated gut microbial communities are key players in shaping the fitness and health of animals. However, most current studies have focused on the gut bacteria, neglecting important gut fungal and archaeal components of these communities. Here, we investigated the gut fungi and archaea community composition in Large White piglets using shotgun metagenomic sequencing, and systematically evaluated how community composition association with gut microbiome, functional capacity, and serum metabolites varied across three weaning periods. Results We found that Mucoromycota, Ascomycota and Basidiomycota were the most common fungi phyla and Euryarchaeota was the most common archaea phyla across individuals. We identified that Methanosarcina siciliae was the most significantly different archaea species among three weaning periods, while Parasitella parasitica, the only differential fungi species, was significantly and positively correlated with Methanosarcina siciliae enriched in day 28 group. The random forest analysis also identified Methanosarcina siciliae and Parasitella parasitica as weaning-biased archaea and fungi at the species level. Additionally, Methanosarcina siciliae was significantly correlated with P. copri and the shifts of functional capacities of the gut microbiome and several CAZymes in day 28 group. Furthermore, characteristic successional alterations in gut archaea, fungi, bacteria, and serum metabolites with each weaning step revealed a weaning transition coexpression network, e.g., Methanosarcina siciliae and P. copri were positively and significantly correlated with 15-HEPE, 8-O-Methyloblongine, and Troxilin B3. Conclusion Our findings provide a deep insight into the interactions among gut archaea, fungi, bacteria, and serum metabolites and will present a theoretical framework for understanding gut bacterial colonization and succession association with archaea during piglet weaning transitions. Supplementary Information The online version contains supplementary material available at 10.1186/s12917-022-03330-4.
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Affiliation(s)
- Xinwei Xiong
- Institute of Biological Technology, Nanchang Normal University, Nanchang, Jiangxi, 330032, People's Republic of China.
| | - Yousheng Rao
- Institute of Biological Technology, Nanchang Normal University, Nanchang, Jiangxi, 330032, People's Republic of China
| | - Xutang Tu
- Institute of Biological Technology, Nanchang Normal University, Nanchang, Jiangxi, 330032, People's Republic of China
| | - Zhangfeng Wang
- Institute of Biological Technology, Nanchang Normal University, Nanchang, Jiangxi, 330032, People's Republic of China
| | - Jishang Gong
- Institute of Biological Technology, Nanchang Normal University, Nanchang, Jiangxi, 330032, People's Republic of China
| | - Yanbei Yang
- Institute of Biological Technology, Nanchang Normal University, Nanchang, Jiangxi, 330032, People's Republic of China
| | - Haobin Wu
- Institute of Biological Technology, Nanchang Normal University, Nanchang, Jiangxi, 330032, People's Republic of China
| | - Xianxian Liu
- Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, People's Republic of China.
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Mohammadzadeh R, Mahnert A, Duller S, Moissl-Eichinger C. Archaeal key-residents within the human microbiome: characteristics, interactions and involvement in health and disease. Curr Opin Microbiol 2022; 67:102146. [PMID: 35427870 DOI: 10.1016/j.mib.2022.102146] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/25/2022] [Accepted: 03/01/2022] [Indexed: 12/13/2022]
Abstract
Since the introduction of Archaea as new domain of life more than 40 years ago, they are no longer regarded as eccentric inhabitants of extreme ecosystems. These microorganisms are widespread in various moderate ecosystems, including eukaryotic hosts such as humans. Indeed, members of the archaeal community are now recognized as paramount constituents of human microbiome, while their definite role in disease or health is not fully elucidated and no archaeal pathogen has been reported. Here, we present a brief overview of archaea residing in and on the human body, with a specific focus on common lineages including Methanobrevibacter, Methanosphaeraand Methanomassilococcales.
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Affiliation(s)
- Rokhsareh Mohammadzadeh
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
| | - Alexander Mahnert
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
| | - Stefanie Duller
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
| | - Christine Moissl-Eichinger
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria; BioTechMed, 8010 Graz, Austria.
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Cai M, Kandalai S, Tang X, Zheng Q. Contributions of Human-Associated Archaeal Metabolites to Tumor Microenvironment and Carcinogenesis. Microbiol Spectr 2022; 10:e0236721. [PMID: 35225671 PMCID: PMC9045267 DOI: 10.1128/spectrum.02367-21] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 01/13/2022] [Indexed: 12/14/2022] Open
Abstract
There is increasing awareness that archaea are interrelated with human diseases (including cancer). Archaea utilize unique metabolic pathways to produce a variety of metabolites that serve as a direct link to host-microbe interactions. However, knowledge on the diversity of human-associated archaea is still extremely limited, and less is known about the pathological effects of their metabolites to the tumor microenvironment and carcinogenesis. In the present study, we performed a large-scale analysis of archaea and their cancer-related metabolites across different body sites using >44,000 contigs with length >1,000 bp. Taxonomy annotation revealed that the occurrence and diversity of archaea are higher in two body sites, the gut and the oral cavity. Unlike other human-associated microbes, the nonmetric multidimensional scaling (NMDS) and permutational multivariate analysis of variance (PERMANOVA) analyses have shown no difference of archaeal compositions between Easterners and Westerners. Likewise, protein annotation suggests that genes encoding cancer-related metabolites (e.g., short-chain fatty acids and polyamines) are more prevalent and diverse in gut and oral samples. Archaea carrying these metabolites are restricted to Euryarchaeota and the TACK superphylum (Thaumarchaeota, Aigarchaeota, Crenarchaeota, and Korarchaeota), especially methanogenic archaea, such as Methanobacteria. IMPORTANCE More evidence suggests that archaea are associated with human disease, including cancer. Here, we present the first framework of the diversity and distribution of human-associated archaea across human body sites, such as gut and oral cavity, using long contigs. Furthermore, we unveiled the potential archaeal metabolites linking to different lineages that might influence the tumor microenvironment and carcinogenesis. These results could open a new door to the guidance of diagnosing cancer and developing new treatment strategies.
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Affiliation(s)
- Mingwei Cai
- Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China
| | - Shruthi Kandalai
- Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
| | - Xiaoyu Tang
- Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China
- School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China
| | - Qingfei Zheng
- Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
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