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Rroji M, Spahia N, Figurek A, Spasovski G. Targeting Diabetic Atherosclerosis: The Role of GLP-1 Receptor Agonists, SGLT2 Inhibitors, and Nonsteroidal Mineralocorticoid Receptor Antagonists in Vascular Protection and Disease Modulation. Biomedicines 2025; 13:728. [PMID: 40149704 PMCID: PMC11940462 DOI: 10.3390/biomedicines13030728] [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: 02/09/2025] [Revised: 03/03/2025] [Accepted: 03/12/2025] [Indexed: 03/29/2025] Open
Abstract
Atherosclerosis is a closely related complication of diabetes mellitus (DM), driven by endothelial dysfunction, inflammation, and oxidative stress. The progression of atherosclerosis is accelerated by hyperglycemia, insulin resistance, and hyperlipidemia. Novel antidiabetic agents, SGLT2 inhibitors, and GLP-1 agonists improve glycemic control and offer cardiovascular protection, reducing the risk of major adverse cardiovascular events (MACEs) and heart failure hospitalization. These agents, along with nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), promise to mitigate metabolic disorders and their impact on endothelial function, oxidative stress, and inflammation. This review explores the potential molecular mechanisms through which these drugs may prevent the development of atherosclerosis and cardiovascular disease (CVD), supported by a summary of preclinical and clinical evidence.
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Affiliation(s)
- Merita Rroji
- Department of Nephrology, University of Medicine Tirana, 1001 Tirana, Albania
- Department of Nephrology, University Hospital Center Mother Tereza, 1001 Tirana, Albania;
| | - Nereida Spahia
- Department of Nephrology, University Hospital Center Mother Tereza, 1001 Tirana, Albania;
| | - Andreja Figurek
- Institute of Anatomy, University of Zurich, 8057 Zurich, Switzerland;
| | - Goce Spasovski
- Department of Nephrology, University Sts. Cyril and Methodius, 1000 Skopje, North Macedonia;
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Ribeiro G, Schellekens H, Cuesta-Marti C, Maneschy I, Ismael S, Cuevas-Sierra A, Martínez JA, Silvestre MP, Marques C, Moreira-Rosário A, Faria A, Moreno LA, Calhau C. A menu for microbes: unraveling appetite regulation and weight dynamics through the microbiota-brain connection across the lifespan. Am J Physiol Gastrointest Liver Physiol 2025; 328:G206-G228. [PMID: 39811913 DOI: 10.1152/ajpgi.00227.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 08/14/2024] [Accepted: 01/02/2025] [Indexed: 01/16/2025]
Abstract
Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut-microbiota-targeted approaches such as pre-, pro-, post-, and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is 1) to provide an overview of the role of the microbiota-gut-brain axis in appetite regulation across the lifespan and 2) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.
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Affiliation(s)
- Gabriela Ribeiro
- Metabolism and Nutrition Department, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- CHRC - Center for Health Technology and Services Research, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Harriët Schellekens
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Cristina Cuesta-Marti
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Ivie Maneschy
- Growth, Exercise, Nutrition and Development Research Group, Instituto Agroalimentario de Aragón, University of Zaragoza, Zaragoza, Spain
- Instituto de Investigación Sanitaria de Aragón, University of Zaragoza, Zaragoza, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Shámila Ismael
- Metabolism and Nutrition Department, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- CHRC - Center for Health Technology and Services Research, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- CINTESIS - Comprehensive Health Research Centre, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Amanda Cuevas-Sierra
- Metabolism and Nutrition Department, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- Precision Nutrition and Cardiometabolic Health, IMDEA-Food Institute (Madrid Institute for Advanced Studies), Campus of International Excellence (CEI) UAM+CSIC, Spanish National Research Council, Madrid, Spain
| | - J Alfredo Martínez
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Precision Nutrition and Cardiometabolic Health, IMDEA-Food Institute (Madrid Institute for Advanced Studies), Campus of International Excellence (CEI) UAM+CSIC, Spanish National Research Council, Madrid, Spain
| | - Marta P Silvestre
- Metabolism and Nutrition Department, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- CHRC - Center for Health Technology and Services Research, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Cláudia Marques
- Metabolism and Nutrition Department, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- CHRC - Center for Health Technology and Services Research, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - André Moreira-Rosário
- Metabolism and Nutrition Department, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- CINTESIS - Comprehensive Health Research Centre, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Ana Faria
- Metabolism and Nutrition Department, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- CHRC - Center for Health Technology and Services Research, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- CINTESIS - Comprehensive Health Research Centre, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Luis A Moreno
- Growth, Exercise, Nutrition and Development Research Group, Instituto Agroalimentario de Aragón, University of Zaragoza, Zaragoza, Spain
- Instituto de Investigación Sanitaria de Aragón, University of Zaragoza, Zaragoza, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Conceição Calhau
- Metabolism and Nutrition Department, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
- CHRC - Center for Health Technology and Services Research, Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
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Ommati MM, Jin Y, Zamiri MJ, Retana-Marquez S, Nategh Ahmadi H, Sabouri S, Song SZ, Heidari R, Wang HW. Sex-Specific Mechanisms of Fluoride-Induced Gonadal Injury: A Multi-Omics Investigation into Reproductive Toxicity and Gut Microbiota Disruption. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:2527-2550. [PMID: 39818830 DOI: 10.1021/acs.jafc.4c10190] [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: 01/19/2025]
Abstract
Fluoride, a common agricultural additive used to enhance plant resilience and pest control, poses toxicity risks when exposure surpasses safe thresholds, affecting ecosystems and human health. While its reproductive toxicity is recognized, the sex-specific and cross-generational effects remain underexplored. To address this gap, we employed an integrative approach combining transcriptomics (next-generation sequencing (NGS)), bioinformatic network analysis, gut microbiota sequencing, and in vivo functional assays. ICR mice (F0 generation), both male and female, were exposed to fluoride (100 mg/L in drinking water) for 35 days, continuing through gestation and offspring weaning. Our transcriptomic analysis revealed significant upregulation of autophagy (via the PI3K-AKT-mTOR pathway) and oxidative stress-induced mitochondrial dysfunction in gonadal tissue, with more pronounced effects observed in males. Further integrated analyses of transcriptomic and metabolomic data, supported by in vivo experiments, highlighted oxidative stress, mitochondrial dysfunction, and PI3K-AKT-mTOR pathway activation with stronger effects in males. The principal component analysis confirmed sex-specific transcriptome alterations, with males showing more substantial disruption. Additionally, 16S rRNA sequencing identified significant gut dysbiosis, particularly in males, with an increased Firmicutes/Bacteroidetes ratio and higher abundances of Oscillospirales and Anaerovoracaceae. Moreover, our study identified significant correlations between specific gut microbiota (e.g., Firmicutes, Proteobacteria) and autophagy, oxidative stress, and mitochondrial dysfunction pathways, with notable sex-dependent differences. These findings suggest that gut microbiota may play a critical role in modulating fluoride-induced reproductive toxicity, particularly through their effects on oxidative stress and cellular homeostasis. The breakdown of the gut barrier and elevated serum/gonadal lipopolysaccharide (LPS) levels in fluoride-treated mice further established a link between gut dysbiosis and fluoride-induced reproductive toxicity. These findings underscore the importance of considering sex differences in xenobiotic-induced reproductive and developmental toxicity.
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Affiliation(s)
- Mohammad Mehdi Ommati
- Henan Key Laboratory of Environmental and Animal Product Safety, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
| | - Ye Jin
- Henan Key Laboratory of Environmental and Animal Product Safety, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Mohammad Javad Zamiri
- Department of Animal Science, Shiraz Agricultural University, Shiraz 71946-84471, Iran
| | - Socorro Retana-Marquez
- Department of Biology of Reproduction, Autonomous Metropolitan University, Iztapalapa, Mexico City 09340, Mexico
| | - Hassan Nategh Ahmadi
- College of Animal Science and Veterinary Medicine, Shiraz University, Shiraz 71946-84471, Iran
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China
| | - Samira Sabouri
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China
| | - Shu Zhe Song
- Henan Key Laboratory of Environmental and Animal Product Safety, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Reza Heidari
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
| | - Hong-Wei Wang
- Henan Key Laboratory of Environmental and Animal Product Safety, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
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Sharma A, Kapur S, Kancharla P, Yang T. Sex differences in gut microbiota, hypertension, and cardiovascular risk. Eur J Pharmacol 2025; 987:177183. [PMID: 39647571 PMCID: PMC11714433 DOI: 10.1016/j.ejphar.2024.177183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 12/04/2024] [Accepted: 12/05/2024] [Indexed: 12/10/2024]
Abstract
The intricate ecosystem of the gut microbiome exhibits sex-specific differences, influencing the susceptibility to cardiovascular diseases (CVD). Imbalance within the gut microbiome compromises the gut barrier, activates inflammatory pathways, and alters the production of metabolites, all of which initiate chronic diseases including CVD. In particular, the interplay between lifestyle choices, hormonal changes, and metabolic byproducts uniquely affects sex-specific gut microbiomes, potentially shaping the risk profiles for hypertension and CVD differently in men and women. Understanding the gut microbiome's role in CVD risk offers informative reasoning behind the importance of developing tailored preventative strategies based on sex-specific differences in CVD risk. Furthermore, insight into the differential impact of social determinants and biological factors on CVD susceptibility emphasizes the necessity for more nuanced approaches. This review also outlines specific dietary interventions that may enhance gut microbiome health, offering a glimpse into potential therapeutic avenues for reducing CVD risk that require greater awareness. Imbalance in natural gut microbiomes may explain etiologies of chronic diseases; we advocate for future application to alter the gut microbiome as possible treatment of the aforementioned diseases. This review mentions the idea of altering the gut microbiome through interventions such as fecal microbiota transplantation (FMT), a major application of microbiome-based therapy that is first-line for Clostridium difficile infections and patient-specific probiotics highlights more innovative approaches to hypertension and CVD prevention. Through increased analysis of gut microbiota compositions along with patient-centric probiotics and microbiome transfers, this review advocates for future preventative strategies for hypertension.
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Affiliation(s)
- Anish Sharma
- Center for Hypertension and Precision Medicine, Microbiome Consortium, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, OH, USA
| | - Sahil Kapur
- Center for Hypertension and Precision Medicine, Microbiome Consortium, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, OH, USA
| | - Priyal Kancharla
- Center for Hypertension and Precision Medicine, Microbiome Consortium, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, OH, USA
| | - Tao Yang
- Center for Hypertension and Precision Medicine, Microbiome Consortium, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, OH, USA.
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Hernandez J, Rodriguez JB, Trak-Fellermeier MA, Galvan R, Macchi A, Martinez-Motta P, Palacios C. Suboptimal vitamin D status and overweight/obesity are associated with gut integrity and inflammation in minority children and adolescents: A cross-sectional analysis from the MetA-bone trial. Nutr Res 2025; 133:13-21. [PMID: 39662375 DOI: 10.1016/j.nutres.2024.11.006] [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: 07/10/2024] [Revised: 11/18/2024] [Accepted: 11/18/2024] [Indexed: 12/13/2024]
Abstract
Preserving gut integrity is essential to preventing the development of chronic diseases. Several factors are associated with gut integrity and inflammation in adults. However, there is limited evidence in healthy children. This study evaluated the factors associated with gut integrity and inflammation in healthy children participating in the MetA-Bone trial. We hypothesized that age, sex, race/ethnicity, diet, vitamin D, and body composition will be associated with gut integrity and inflammation. Socio-demographic variables were collected with a questionnaire. Measures included markers of gut integrity (Intestinal Fatty Acid Binding Protein; I-FABP), and inflammation (IL-17 and calprotectin) determined by ELISA in 24-h urine and serum; serum 25(OH)D concentration (commercial lab), BMI percentile, and diet (24-h recalls). Analyses included descriptive statistics, chi-square, and adjusted logistic regressions. Participants (n=138) median age was 12.4 (11.1-13.3), 53.6% were male, 9.4% were Black/African American, and 71.1% were Hispanic/Latino. Children with suboptimal vitamin D were 3.35 times more likely to present gut integrity damage (elevated I-FABP) than those with optimal status (P = .005). Overweight/obesity and fructose intake were associated with inflammation (elevated calprotectin) (P < .05). Those with lower gut integrity damage had lower odds of having higher inflammation (P = .021). Other factors were not associated with inflammation. Suboptimal vitamin D status, overweight/obesity and inflammation may compromise the gut integrity in healthy children, suggesting an impairment on the intestinal barrier repair system. More research with a longitudinal design is needed to gain a deeper understanding of the role of additional factors linked to gut integrity and inflammation in healthy children.
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Affiliation(s)
- Jacqueline Hernandez
- Department of Dietetics and Nutrition, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL, USA.
| | - Jose Bastida Rodriguez
- Department of Dietetics and Nutrition, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL, USA
| | - Maria Angelica Trak-Fellermeier
- Department of Dietetics and Nutrition, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL, USA
| | - Rodolfo Galvan
- Department of Dietetics and Nutrition, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL, USA
| | - Alison Macchi
- Department of Dietetics and Nutrition, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL, USA
| | - Preciosa Martinez-Motta
- Department of Dietetics and Nutrition, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL, USA
| | - Cristina Palacios
- Department of Dietetics and Nutrition, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL, USA
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Wang S, Li J, Liu WH, Li N, Liang H, Hung W, Jiang Q, Cheng R, Shen X, He F. Lacticaseibacillus paracasei K56 inhibits lipid accumulation in adipocytes by promoting lipolysis. FOOD SCIENCE AND HUMAN WELLNESS 2024; 13:3511-3521. [DOI: 10.26599/fshw.2023.9250034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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7
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Chaudhary S, Kaur P, Singh TA, Bano KS, Vyas A, Mishra AK, Singh P, Mehdi MM. The dynamic crosslinking between gut microbiota and inflammation during aging: reviewing the nutritional and hormetic approaches against dysbiosis and inflammaging. Biogerontology 2024; 26:1. [PMID: 39441393 DOI: 10.1007/s10522-024-10146-2] [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: 08/02/2024] [Accepted: 10/01/2024] [Indexed: 10/25/2024]
Abstract
The early-life gut microbiota (GM) is increasingly recognized for its contributions to human health and disease over time. Microbiota composition, influenced by factors like race, geography, lifestyle, and individual differences, is subject to change. The GM serves dual roles, defending against pathogens and shaping the host immune system. Disruptions in microbial composition can lead to immune dysregulation, impacting defense mechanisms. Additionally, GM aids digestion, releasing nutrients and influencing physiological systems like the liver, brain, and endocrine system through microbial metabolites. Dysbiosis disrupts intestinal homeostasis, contributing to age-related diseases. Recent studies are elucidating the bacterial species that characterize a healthy microbiota, defining what constitutes a 'healthy' colonic microbiota. The present review article focuses on the importance of microbiome composition for the development of homeostasis and the roles of GM during aging and the age-related diseases caused by the alteration in gut microbial communities. This article might also help the readers to find treatments targeting GM for the prevention of various diseases linked to it effectively.
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Affiliation(s)
- Sakshi Chaudhary
- Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Pardeep Kaur
- Department of Biotechnology, Chandigarh University, Mohali, Punjab, 140413, India
| | - Thokchom Arjun Singh
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Kaniz Shahar Bano
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Ashish Vyas
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Alok Kumar Mishra
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Prabhakar Singh
- Department of Biotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, 600119, India
| | - Mohammad Murtaza Mehdi
- Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India.
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Sasidharan Pillai S, Gagnon CA, Foster C, Ashraf AP. Exploring the Gut Microbiota: Key Insights Into Its Role in Obesity, Metabolic Syndrome, and Type 2 Diabetes. J Clin Endocrinol Metab 2024; 109:2709-2719. [PMID: 39040013 PMCID: PMC11479700 DOI: 10.1210/clinem/dgae499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 06/22/2024] [Accepted: 07/16/2024] [Indexed: 07/24/2024]
Abstract
The gut microbiota (GM), comprising trillions of microorganisms in the gastrointestinal tract, is a key player in the development of obesity and related metabolic disorders, such as type 2 diabetes (T2D), metabolic syndrome (MS), and cardiovascular diseases. This mini-review delves into the intricate roles and mechanisms of the GM in these conditions, offering insights into potential therapeutic strategies targeting the microbiota. The review elucidates the diversity and development of the human GM, highlighting its pivotal functions in host physiology, including nutrient absorption, immune regulation, and energy metabolism. Studies show that GM dysbiosis is linked to increased energy extraction, altered metabolic pathways, and inflammation, contributing to obesity, MS, and T2D. The interplay between dietary habits and GM composition is explored, underscoring the influence of diet on microbial diversity and metabolic functions. Additionally, the review addresses the impact of common medications and therapeutic interventions like fecal microbiota transplantation on GM composition. The evidence so far advocates for further research to delineate the therapeutic potential of GM modulation in mitigating obesity and metabolic diseases, emphasizing the necessity of clinical trials to establish effective and sustainable treatment protocols.
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Affiliation(s)
- Sabitha Sasidharan Pillai
- Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA
- Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Charles A Gagnon
- University of Alabama at Birmingham Marnix E. Heersink School of Medicine, Birmingham, AL 35294, USA
| | - Christy Foster
- Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Ambika P Ashraf
- Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Li Z, Liu Y, Wang Y, Cai Q, Wang Y, Bai Y, Liu H, Xu C, Zhang F. Sodium oligomannate's amelioration of reproductive and metabolic phenotypes in a letrozole-induced PCOS-like mouse model depends on the gut microbiome†. Biol Reprod 2024; 111:361-375. [PMID: 38630889 DOI: 10.1093/biolre/ioae058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 03/25/2024] [Accepted: 04/16/2024] [Indexed: 04/19/2024] Open
Abstract
It has been well established that there is a connection between polycystic ovary syndrome pathology and gut microbiome dysbiosis. A marine-derived oligosaccharide, GV-971, has been reported to alter gut microbiota and alleviate Aβ amyloidosis. In this study, the effects of GV-971 on polycystic ovary syndrome-like mice were explored. Mice were randomly assigned into four groups: control, letrozole, letrozole + GV-971, and control + GV-971. Glucose metabolism in polycystic ovary syndrome-like mice was ameliorated by GV-971, while the reproductive endocrine disorder of polycystic ovary syndrome-like mice was partially reversed. The messenger ribonucleic acid levels of steroidogenic enzymes in ovaries of polycystic ovary syndrome-like mice were improved. GV-971 restored the fertility of polycystic ovary syndrome-like mice and significantly increase the number of litters. Furthermore, GV-971 treatment effectively mitigated abnormal bile acid metabolism. Notably, after GV-971 intervention, gut microbiota alpha-diversity was considerably raised and the relative abundance of Firmicutes was reduced. In conclusion, the hyperinsulinemia and hyperandrogenemia of polycystic ovary syndrome-like mice were alleviated by GV-971 intervention, which was associated with mitigating bile acid metabolism and modulating gut microbiota.
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Affiliation(s)
- Zhi Li
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Yan Liu
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Yang Wang
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Qingqing Cai
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
| | - Yuhui Wang
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Yixuan Bai
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Haiou Liu
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
| | - Congjian Xu
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
- Department of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai, China
| | - Feifei Zhang
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Department of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai, China
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10
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Liang Y, Jiang Z, Fu Y, Lu S, Miao Z, Shuai M, Liang X, Gou W, Zhang K, Shi RQ, Gao C, Shi MQ, Wang XH, Hu WS, Zheng JS. Cross-Sectional and Prospective Association of Serum 25-Hydroxyvitamin D with Gut Mycobiota during Pregnancy among Women with Gestational Diabetes. Mol Nutr Food Res 2024; 68:e2400022. [PMID: 38763911 DOI: 10.1002/mnfr.202400022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 04/30/2024] [Indexed: 05/21/2024]
Abstract
SCOPE Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.
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Affiliation(s)
- Yuhui Liang
- College of Life Sciences, Zhejiang University, Hangzhou, 310058, China
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
| | - Zengliang Jiang
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, 310024, China
| | - Yuanqing Fu
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, 310024, China
| | - Sha Lu
- Department of Obstetrics and Gynecology, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, 310012, China
- Department of Obstetrics and Gynecology, The Affiliated Hangzhou Women's Hospital of Hangzhou Normal University, Hangzhou, 310012, China
| | - Zelei Miao
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, 310024, China
| | - Menglei Shuai
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
| | - Xinxiu Liang
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
| | - Wanglong Gou
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, 310024, China
| | - Ke Zhang
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
| | - Rui-Qi Shi
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
| | - Chang Gao
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
| | - Mei-Qi Shi
- Department of Nutrition, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, 310012, China
| | - Xu-Hong Wang
- Department of Nutrition, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, 310012, China
| | - Wen-Sheng Hu
- Department of Obstetrics and Gynecology, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, 310012, China
- Department of Obstetrics and Gynecology, The Affiliated Hangzhou Women's Hospital of Hangzhou Normal University, Hangzhou, 310012, China
| | - Ju-Sheng Zheng
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, China
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310030, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, 310024, China
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11
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Sechovcová H, Mahayri TM, Mrázek J, Jarošíková R, Husáková J, Wosková V, Fejfarová V. Gut microbiota in relationship to diabetes mellitus and its late complications with a focus on diabetic foot syndrome: A review. Folia Microbiol (Praha) 2024; 69:259-282. [PMID: 38095802 DOI: 10.1007/s12223-023-01119-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 12/05/2023] [Indexed: 04/11/2024]
Abstract
Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.
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Affiliation(s)
- Hana Sechovcová
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, CAS, Vídeňská, 1083, 142 20, Prague, Czech Republic
- Faculty of Agrobiology, Food and Natural Resources, Department of Microbiology, Nutrition and Dietetics, Czech University of Life Sciences, Prague, Czech Republic
| | - Tiziana Maria Mahayri
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, CAS, Vídeňská, 1083, 142 20, Prague, Czech Republic.
- Department of Veterinary Medicine, University of Sassari, 07100, Sassari, Italy.
| | - Jakub Mrázek
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, CAS, Vídeňská, 1083, 142 20, Prague, Czech Republic
| | - Radka Jarošíková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jitka Husáková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Veronika Wosková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Vladimíra Fejfarová
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Second Faculty of Medicine, Charles University, Prague, Czech Republic
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12
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Gu Y, Zheng S, Huang C, Cao X, Liu P, Zhuang Y, Li G, Hu G, Gao X, Guo X. Microbial colony sequencing combined with metabolomics revealed the effects of chronic hexavalent chromium and nickel combined exposure on intestinal inflammation in mice. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 915:169853. [PMID: 38218477 DOI: 10.1016/j.scitotenv.2023.169853] [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: 12/01/2023] [Revised: 12/30/2023] [Accepted: 12/30/2023] [Indexed: 01/15/2024]
Abstract
The pollution and toxic effects of hexavalent chromium [Cr(VI)] and divalent nickel [Ni(II)] have become worldwide public health issues. However, the potential detailed effects of chronic combined Cr(VI) and Ni exposure on colonic inflammation in mice have not been reported. In this study, 16S rDNA sequencing, metabolomics data analysis, qPCR and other related experimental techniques were used to comprehensively explore the mechanism of toxic damage and the inflammatory response of the colon in mice under the co-toxicity of chronic hexavalent chromium and nickel. The results showed that long-term exposure to Cr(VI) and/or Ni resulted in an imbalance of trace elements in the colon of mice with significant inflammatory infiltration of tissues. Moreover, Cr(VI) and/or Ni poisoning upregulated the expression levels of IL-6, IL-18, IL-1β, TNF-α, IFN-γ, JAK2 and STAT3 mRNA, and downregulated IL-10 mRNA, which was highly consistent with the trend in protein expression. Combined with multiomics analysis, Cr(VI) and/or Ni could change the α diversity and β diversity of the gut microbiota and induce significant differential changes in metabolites such as Pyroglu-Glu-Lys, Val-Asp-Arg, stearidonic acid, and 20-hydroxyarachidonic acid. They are also associated with disorders of important metabolic pathways such as lipid metabolism and amino acid metabolism. Correlation analysis revealed that there was a significant correlation between gut microbes and metabolites (P < 0.05). In summary, based on the advantages of comprehensive analysis of high-throughput sequencing sets, these results suggest that chronic exposure to Cr(VI) and Ni in combination can cause microbial flora imbalances, induce metabolic disorders, and subsequently cause colonic damage in mice. These data provide new insights into the toxicology and molecular mechanisms of Cr(VI) and Ni.
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Affiliation(s)
- Yueming Gu
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
| | - Shuangyan Zheng
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China; Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, China
| | - Cheng Huang
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
| | - Xianhong Cao
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
| | - Ping Liu
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
| | - Yu Zhuang
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
| | - Guyue Li
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
| | - Guoliang Hu
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
| | - Xiaona Gao
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
| | - Xiaoquan Guo
- Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China.
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13
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Lan Y, Hu Y, Guo Y, Ali F, Amjad N, Ouyang Q, Almutairi MH, Wang D. Microbiome analysis reveals the differences in gut fungal community between Dutch Warmblood and Mongolian horses. Microb Pathog 2024; 188:106566. [PMID: 38309310 DOI: 10.1016/j.micpath.2024.106566] [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: 08/31/2023] [Revised: 01/27/2024] [Accepted: 01/31/2024] [Indexed: 02/05/2024]
Abstract
Similar to gut bacterial community, gut fungal community are also an important part of the gut microbiota and play crucial roles in host immune regulation and metabolism. However, most studies have focused on the gut bacterial community, and research on the gut fungal community has been limited. Dutch Warmblood (DWH) and Mongolian horses (MGH) are important equine breeds, but little research has been done on their gut fungal community. Here, we assessed differences in gut fungal community between two horse species. Results showed that a total of 2159 OTUs were found in the Dutch Warmblood and Mongolian horses, of which 308 were common. Between-group analyzes of microbial diversity showed no differences in the alpha and beta diversity of gut fungal community between the two horse species. Microbiological taxonomic surveys showed that the dominant fungal phyla (Neocallimastigomycota and Ascomycota) and genera (unclassified_Neocallimastigaceae and Anaeromyces) were the same without being affected by species. Although the types of dominant fungal phyla did not change, the abundances of some fungal genera changed significantly. Results of Metastats analysis showed that there were a total of 206 fungal genera that were significantly different between the two horses, among which 78 genera showed an increase and 127 genera significantly decreased in Dutch Warmblood horses compared with Mongolian horses. In conclusion, this study investigated the composition and structure of the gut fungal community of Dutch Warmblood and Mongolian horses and found significant differences in gut fungal community between both breeds. Notably, this is the first exploration of the differences in the gut fungal community of both breeds, which may help to understand the distribution characteristics of the gut fungal community of different breeds of horses and reveal the differences in the traits of different horses.
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Affiliation(s)
- Yanfang Lan
- Wuhan Business University, Wuhan, 430100, China
| | - Yunyun Hu
- Wuhan Business University, Wuhan, 430100, China
| | | | - Farah Ali
- Faculty of Veterinary and Animal Sciences, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan
| | - Nouman Amjad
- Faculty of Veterinary and Animal Sciences, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan
| | | | - Mikhlid H Almutairi
- Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Dongjing Wang
- Institute of Animal Husbandry and Veterinary, Tibet Autonomous Regional Academy of Agricultural Sciences, Lhasa City, Tibet, 850009, China; State Key Laboratory of Highland Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa City, Tibet, 850009, China.
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14
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Hiltzik DM, Goodwin AM, Kurapaty SS, Inglis JE, Pagadala MS, Edelstein AI, Hsu WK. The Role of the Gut Microbiome in Orthopedic Surgery-a Narrative Review. Curr Rev Musculoskelet Med 2024; 17:37-46. [PMID: 38133764 PMCID: PMC10805751 DOI: 10.1007/s12178-023-09878-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/07/2023] [Indexed: 12/23/2023]
Abstract
PURPOSE OF REVIEW The importance of the gut microbiome has received increasing attention in recent years. New literature has revealed significant associations between gut health and various orthopedic disorders, as well as the potential for interventions targeting the gut microbiome to prevent disease and improve musculoskeletal outcomes. We provide a broad overview of available literature discussing the links between the gut microbiome and pathogenesis and management of orthopedic disorders. RECENT FINDINGS Human and animal models have characterized the associations between gut microbiome dysregulation and diseases of the joints, spine, nerves, and muscle, as well as the physiology of bone formation and fracture healing. Interventions such as probiotic supplementation and fecal transplant have shown some promise in ameliorating the symptoms or slowing the progression of these disorders. We aim to aid discussions regarding optimization of patient outcomes in the field of orthopedic surgery by providing a narrative review of the available evidence-based literature involving gut microbiome dysregulation and its effects on orthopedic disease. In general, we believe that the gut microbiome is a viable target for interventions that can augment current management models and lead to significantly improved outcomes for patients under the care of orthopedic surgeons.
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Affiliation(s)
- David M Hiltzik
- Department of Orthopaedic Surgery, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60622, USA
| | - Alyssa M Goodwin
- Department of Orthopaedic Surgery, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60622, USA
| | - Steven S Kurapaty
- Department of Orthopaedic Surgery, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60622, USA
- Department of Orthopaedic Surgery, Howard University, Washington, DC, USA
| | - Jacqueline E Inglis
- Department of Orthopaedic Surgery, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60622, USA
| | - Manasa S Pagadala
- Department of Orthopaedic Surgery, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60622, USA.
| | - Adam I Edelstein
- Department of Orthopaedic Surgery, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60622, USA
| | - Wellington K Hsu
- Department of Orthopaedic Surgery, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60622, USA
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15
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Jiao X, Liu B, Dong X, Wang S, Cai X, Zhang H, Qin Z. Exploring PLGA-OH-CATH30 Microspheres for Oral Therapy of Escherichia coli-Induced Enteritis. Biomolecules 2024; 14:86. [PMID: 38254686 PMCID: PMC10813405 DOI: 10.3390/biom14010086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/20/2023] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
Antibiotic therapy effectively addresses Escherichia coli-induced enteric diseases, but its excessive utilization results in microbial imbalance and heightened resistance. This study evaluates the therapeutic efficacy of orally administered poly (lactic-co-glycolic acid) (PLGA)-loaded antimicrobial peptide OH-CATH30 microspheres in murine bacterial enteritis. Mice were categorized into the healthy control group (CG), untreated model group (MG), OH-CATH30 treatment group (OC), PLGA-OH-CATH30 treatment group (POC), and gentamicin sulfate treatment group (GS). Except for the control group, all other experimental groups underwent Escherichia coli-induced enteritis, followed by a 5-day treatment period. The evaluation encompassed clinical symptoms, intestinal morphology, blood parameters, inflammatory response, and gut microbiota. PLGA-OH-CATH30 microspheres significantly alleviated weight loss and intestinal damage while also reducing the infection-induced increase in spleen index. Furthermore, these microspheres normalized white blood cell count and neutrophil ratio, suppressed inflammatory factors (IL-1β, IL-6, and TNF-α), and elevated the anti-inflammatory factor IL-10. Analysis of 16S rRNA sequencing results demonstrated that microsphere treatment increased the abundance of beneficial bacteria, including Phocaeicola vulgatus, in the intestinal tract while concurrently decreasing the abundance of pathogenic bacteria, such as Escherichia. In conclusion, PLGA-OH-CATH30 microspheres have the potential to ameliorate intestinal damage and modulate the intestinal microbiota, making them a promising alternative to antibiotics for treating enteric diseases induced by Escherichia coli.
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Affiliation(s)
| | | | | | | | | | | | - Zhihua Qin
- College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, China; (X.J.); (B.L.); (X.D.); (S.W.); (X.C.); (H.Z.)
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16
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Lan X, Ma J, Huang Z, Xu Y, Hu Y. Akkermansia muciniphila might improve anti-PD-1 therapy against HCC by changing host bile acid metabolism. J Gene Med 2024; 26:e3639. [PMID: 38058259 DOI: 10.1002/jgm.3639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 09/26/2023] [Accepted: 11/01/2023] [Indexed: 12/08/2023] Open
Abstract
PD-1 monoclonal antibodies (mAb) have demonstrated remarkable efficacy in a variety of cancers, including Hepatocellular carcinoma (HCC). However, the patient response rates remain suboptimal, and a significant proportion of initial responders may develop resistance to this therapeutic approach. Akkermansia muciniphila (AKK), a microorganism implicated in multiple human diseases, has been reported to be more abundant in patients who exhibit favorable responses to PD-1mAb. However, the underlying mechanism has yet to be elucidated. In our study, we found that AKK could enhance the efficacy of PD-1mAb against HCC in a tumor-bearing mouse model. It promotes HCC tumor cells apoptosis and raise the CD8+ T proportion in the tumor microenvironment. Additionally, AKK downregulates PD-L1 expression in tumor cells. Furthermore, the analysis of metabonomics demonstrates that AKK induces alterations in the host's bile acid metabolism, leading to a significant increase in serum TUDCA levels. Considering the immunosuppresive roles of TUDCA in HCC development, it is plausible to speculate that AKK may reinforce the immunotherapy of PD-1mAb against HCC through its impact on bile acid metabolism.
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Affiliation(s)
- Xiucai Lan
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiaming Ma
- Department of Health-Related Product Assessment, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Zhipeng Huang
- Department of Gastroenterology, First Hospital of Quanzhou affiliated to Fujian Medical University, Quanzhou, China
| | - Yuzhen Xu
- Department of Rehabilitation, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Yaomin Hu
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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17
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Patil RS, Tupe RS. Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis. Med Res Rev 2024; 44:365-405. [PMID: 37589449 DOI: 10.1002/med.21987] [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: 09/23/2022] [Revised: 07/12/2023] [Accepted: 08/06/2023] [Indexed: 08/18/2023]
Abstract
Diabetes and its complications, Alzheimer's disease (AD), and Parkinson's disease (PD) are increasing gradually, reflecting a global threat vis-à-vis expressing the essentiality of a substantial paradigm shift in research and remedial actions. Protein glycation is influenced by several factors, like time, temperature, pH, metal ions, and the half-life of the protein. Surprisingly, most proteins associated with metabolic and neurodegenerative disorders are generally long-lived and hence susceptible to glycation. Remarkably, proteins linked with diabetes, AD, and PD share this characteristic. This modulates protein's structure, aggregation tendency, and toxicity, highlighting renovated attention. Gut microbes and microbial metabolites marked their importance in human health and diseases. Though many scientific shreds of evidence are proposed for possible change and dysbiosis in gut flora in these diseases, very little is known about the mechanisms. Screening and unfolding their functionality in metabolic and neurodegenerative disorders is essential in hunting the gut treasure. Therefore, it is imperative to evaluate the role of glycation as a common link in diabetes and neurodegenerative diseases, which helps to clarify if modulation of nonenzymatic glycation may act as a beneficial therapeutic strategy and gut microbes/metabolites may answer some of the crucial questions. This review briefly emphasizes the common functional attributes of glycation and gut microbes, the possible linkages, and discusses current treatment options and therapeutic challenges.
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Affiliation(s)
- Rahul Shivaji Patil
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
| | - Rashmi Santosh Tupe
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Pune, Maharashtra, India
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18
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Mishra SP, Wang B, Jain S, Ding J, Rejeski J, Furdui CM, Kitzman DW, Taraphder S, Brechot C, Kumar A, Yadav H. A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut. Gut 2023; 72:1848-1865. [PMID: 36948576 PMCID: PMC10512000 DOI: 10.1136/gutjnl-2022-327365] [Citation(s) in RCA: 82] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 03/02/2023] [Indexed: 03/24/2023]
Abstract
OBJECTIVE Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability ('leaky gut') in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive. DESIGN In this study, we substantiate the causal role of the gut microbiota by use of faecal conditioned media along with faecal microbiota transplantation. Using untargeted and comprehensive approaches, we discovered the mechanism by which the obese microbiota instigates gut permeability, inflammation and abnormalities in glucose metabolism. RESULTS We demonstrated that the reduced capacity of the microbiota from both obese mice and humans to metabolise ethanolamine results in ethanolamine accumulation in the gut, accounting for induction of intestinal permeability. Elevated ethanolamine increased the expression of microRNA-miR-101a-3p by enhancing ARID3a binding on the miR promoter. Increased miR-101a-3p decreased the stability of zona occludens-1 (Zo1) mRNA, which in turn, weakened intestinal barriers and induced gut permeability, inflammation and abnormalities in glucose metabolism. Importantly, restoring ethanolamine-metabolising activity in gut microbiota using a novel probiotic therapy reduced elevated gut permeability, inflammation and abnormalities in glucose metabolism by correcting the ARID3a/miR-101a/Zo1 axis. CONCLUSION Overall, we discovered that the reduced capacity of obese microbiota to metabolise ethanolamine instigates gut permeability, inflammation and glucose metabolic dysfunctions, and restoring ethanolamine-metabolising capacity by a novel probiotic therapy reverses these abnormalities. TRIAL REGISTRATION NUMBER NCT02869659 and NCT03269032.
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Affiliation(s)
- Sidharth P Mishra
- Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, USA
- USF Center for Microbiome Research, Microbiomes Institutes, University of South Florida Morsani College of Medicine, Tampa, Florida, USA
| | - Bo Wang
- Department of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, Melbourne, Florida, USA
| | - Shalini Jain
- Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, USA
- USF Center for Microbiome Research, Microbiomes Institutes, University of South Florida Morsani College of Medicine, Tampa, Florida, USA
| | - Jingzhong Ding
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Jared Rejeski
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Cristina M Furdui
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Dalane W Kitzman
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
- Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Subhash Taraphder
- Department of Animal Genetics and Breeding, West Bengal University of Animal & Fishery Sciences, Kolkata, West Bengal, India
| | - Christian Brechot
- Deparment of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida, USA
| | - Ambuj Kumar
- Deparment of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida, USA
| | - Hariom Yadav
- Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, USA
- USF Center for Microbiome Research, Microbiomes Institutes, University of South Florida Morsani College of Medicine, Tampa, Florida, USA
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19
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Kazura W, Michalczyk K, Stygar D. The Relationship between the Source of Dietary Animal Fats and Proteins and the Gut Microbiota Condition and Obesity in Humans. Nutrients 2023; 15:3082. [PMID: 37513500 PMCID: PMC10385089 DOI: 10.3390/nu15143082] [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: 06/09/2023] [Revised: 07/04/2023] [Accepted: 07/06/2023] [Indexed: 07/30/2023] Open
Abstract
The relationship between gut microbiota and obesity is well documented in humans and animal models. Dietary factors can change the intestinal microbiota composition and influence obesity development. However, knowledge of how diet, metabolism, and intestinal microbiota interact and modulate energy metabolism and obesity development is still limited. Epidemiological studies show a link between consuming dietary proteins and fats from specific sources and obesity. Animal studies confirm that proteins and fats of different origins differ in their ability to prevent or induce obesity. Protein sources, such as meat, dairy products, vegetables, pulses, and seafood, vary in their amino acid composition. In addition, the type and level of other factors, such as fatty acids or persistent organic pollutants, vary depending on the source of dietary protein. All these factors can modulate the intestinal microbiota composition and, thus, may influence obesity development. This review summarizes selected evidence of how proteins and fats of different origins affect energy efficiency, obesity development, and intestinal microbiota, linking protein and fat-dependent changes in the intestinal microbiota with obesity.
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Affiliation(s)
- Wojciech Kazura
- Department of Physiology, Faculty of Medical Sciences, Medical University of Silesia, Jordana Street 19, 41-808 Zabrze, Poland
| | - Katarzyna Michalczyk
- Department of Physiology, Faculty of Medical Sciences, Medical University of Silesia, Jordana Street 19, 41-808 Zabrze, Poland
| | - Dominika Stygar
- Department of Physiology, Faculty of Medical Sciences, Medical University of Silesia, Jordana Street 19, 41-808 Zabrze, Poland
- SLU University Animal Hospital, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden
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20
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Ciarambino T, Crispino P, Leto G, Minervini G, Para O, Giordano M. Microbiota and Glucidic Metabolism: A Link with Multiple Aspects and Perspectives. Int J Mol Sci 2023; 24:10409. [PMID: 37373556 DOI: 10.3390/ijms241210409] [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: 05/22/2023] [Revised: 06/12/2023] [Accepted: 06/14/2023] [Indexed: 06/29/2023] Open
Abstract
The global prevalence of overweight and obesity has dramatically increased in the last few decades, with a significant socioeconomic burden. In this narrative review, we include clinical studies aiming to provide the necessary knowledge on the role of the gut microbiota in the development of diabetic pathology and glucose-metabolism-related disorders. In particular, the role of a certain microbial composition of the fermentative type seems to emerge without a specific link to the development in certain subjects of obesity and the chronic inflammation of the adipose tissues, which underlies the pathological development of all the diseases related to glucose metabolism and metabolic syndrome. The gut microbiota plays an important role in glucose tolerance. Conclusion. New knowledge and new information is presented on the development of individualized therapies for patients affected by all the conditions related to reduced glucose tolerance and insulin resistance.
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Affiliation(s)
- Tiziana Ciarambino
- Internal Medicine Department, Hospital of Marcianise, ASL Caserta, 81037 Caserta, Italy
| | - Pietro Crispino
- Internal Medicine Department, Hospital of Latina, ASL Latina, 04100 Latina, Italy
| | - Gaetano Leto
- Department of Experimental Medicine, University La Sapienza Roma, 00185 Rome, Italy
| | - Giovanni Minervini
- Internal Medicine Department, Hospital of Lagonegro, AOR San Carlo, 85042 Lagonegro, Italy
| | - Ombretta Para
- Internal Emergency Department, Hospital of Careggi, University of Florence, 50121 Florence, Italy
| | - Mauro Giordano
- Department of Medical Science, University of Campania, L. Vanvitelli, 81100 Naples, Italy
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21
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Manilla V, Santopaolo F, Gasbarrini A, Ponziani FR. Type 2 Diabetes Mellitus and Liver Disease: Across the Gut-Liver Axis from Fibrosis to Cancer. Nutrients 2023; 15:nu15112521. [PMID: 37299482 DOI: 10.3390/nu15112521] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/23/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
Type 2 diabetes mellitus is a widespread disease worldwide, and is one of the cornerstones of metabolic syndrome. The existence of a strong relationship between diabetes and the progression of liver fibrosis has been demonstrated by several studies, using invasive and noninvasive techniques. Patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) show faster progression of fibrosis than patients without diabetes. Many confounding factors make it difficult to determine the exact mechanisms involved. What we know so far is that both liver fibrosis and T2DM are expressions of metabolic dysfunction, and we recognize similar risk factors. Interestingly, both are promoted by metabolic endotoxemia, a low-grade inflammatory condition caused by increased endotoxin levels and linked to intestinal dysbiosis and increased intestinal permeability. There is broad evidence on the role of the gut microbiota in the progression of liver disease, through both metabolic and inflammatory mechanisms. Therefore, dysbiosis that is associated with diabetes can act as a modifier of the natural evolution of NAFLD. In addition to diet, hypoglycemic drugs play an important role in this scenario, and their benefit is also the result of effects exerted in the gut. Here, we provide an overview of the mechanisms that explain why diabetic patients show a more rapid progression of liver disease up to hepatocellular carcinoma (HCC), focusing especially on those involving the gut-liver axis.
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Affiliation(s)
- Vittoria Manilla
- Digestive Disease Center-CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Santopaolo
- Digestive Disease Center-CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center-CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Digestive Disease Center-CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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22
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Planchette AL, Schmidt C, Burri O, Gomez de Agüero M, Radenovic A, Mylonas A, Extermann J. Optical imaging of the small intestine immune compartment across scales. Commun Biol 2023; 6:352. [PMID: 37002381 PMCID: PMC10066397 DOI: 10.1038/s42003-023-04642-3] [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: 03/24/2022] [Accepted: 02/28/2023] [Indexed: 04/03/2023] Open
Abstract
The limitations of 2D microscopy constrain our ability to observe and understand tissue-wide networks that are, by nature, 3-dimensional. Optical projection tomography (OPT) enables the acquisition of large volumes (ranging from micrometres to centimetres) in various tissues. We present a multi-modal workflow for the characterization of both structural and quantitative parameters of the mouse small intestine. As proof of principle, we evidence its applicability for imaging the mouse intestinal immune compartment and surrounding mucosal structures. We quantify the volumetric size and spatial distribution of Isolated Lymphoid Follicles (ILFs) and quantify the density of villi throughout centimetre-long segments of intestine. Furthermore, we exhibit the age and microbiota dependence for ILF development, and leverage a technique that we call reverse-OPT for identifying and homing in on regions of interest. Several quantification capabilities are displayed, including villous density in the autofluorescent channel and the size and spatial distribution of the signal of interest at millimetre-scale volumes. The concatenation of 3D imaging with reverse-OPT and high-resolution 2D imaging allows accurate localisation of ROIs and adds value to interpretations made in 3D. Importantly, OPT may be used to identify sparsely-distributed regions of interest in large volumes whilst retaining compatibility with high-resolution microscopy modalities, including confocal microscopy. We believe this pipeline to be approachable for a wide-range of specialties, and to provide a new method for characterisation of the mouse intestinal immune compartment.
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Affiliation(s)
- Arielle Louise Planchette
- Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
| | - Cédric Schmidt
- HEPIA/HES-SO, University of Applied Sciences of Western Switzerland, Rue de la Prairie 4, 1202, Geneva, Switzerland
| | - Olivier Burri
- BioImaging & Optics Platform, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland
| | - Mercedes Gomez de Agüero
- Host-microbial interactions group, Institute of Systems Immunology, Max Planck research group, University of Würzburg, Würzburg, Germany
- Mucosal Immunology Group, Department for Biomedical Research, University of Bern, Bern, Switzerland
| | - Aleksandra Radenovic
- Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
| | - Alessio Mylonas
- Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland
| | - Jérôme Extermann
- HEPIA/HES-SO, University of Applied Sciences of Western Switzerland, Rue de la Prairie 4, 1202, Geneva, Switzerland
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23
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Mu J, Guo Z, Wang X, Wang X, Fu Y, Li X, Zhu F, Hu G, Ma X. Seaweed polysaccharide relieves hexavalent chromium-induced gut microbial homeostasis. Front Microbiol 2023; 13:1100988. [PMID: 36726569 PMCID: PMC9884827 DOI: 10.3389/fmicb.2022.1100988] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 12/15/2022] [Indexed: 01/19/2023] Open
Abstract
Heavy metals released in the environment pose a huge threat to soil and water quality, food safety and public health. Additionally, humans and other mammals may also be directly exposed to heavy metals or exposed to heavy metals through the food chain, which seriously threatens the health of animals and humans. Chromium, especially hexavalent chromium [Cr (VI)], as a common heavy metal, has been shown to cause serious environmental pollution as well as intestinal damage. Thus, increasing research is devoted to finding drugs to mitigate the negative health effects of hexavalent chromium exposure. Seaweed polysaccharides have been demonstrated to have many pharmacological effects, but whether it can alleviate gut microbial dysbiosis caused by hexavalent chromium exposure has not been well characterized. Here, we hypothesized that seaweed polysaccharides could alleviate hexavalent chromium exposure-induced poor health in mice. Mice in Cr and seaweed polysaccharide treatment group was compulsively receive K2Cr2O7. At the end of the experiment, all mice were euthanized, and colon contents were collected for DNA sequencing analysis. Results showed that seaweed polysaccharide administration can restore the gut microbial dysbiosis and the reduction of gut microbial diversity caused by hexavalent chromium exposure in mice. Hexavalent chromium exposure also caused significant changes in the gut microbial composition of mice, including an increase in some pathogenic bacteria and a decrease in beneficial bacteria. However, seaweed polysaccharides administration could ameliorate the composition of gut microbiota. In conclusion, this study showed that seaweed polysaccharides can restore the negative effects of hexavalent chromium exposure in mice, including gut microbial dysbiosis. Meanwhile, this research also lays the foundation for the application of seaweed polysaccharides.
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Affiliation(s)
- Jinghao Mu
- Department of Urology, Chinese PLA General Hospital, Beijing, China,Department of Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhenhuan Guo
- Zhengzhou Key Laboratory of Immunopharmacology of Traditional Chinese Veterinary Medicines, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China,*Correspondence: Zhenhuan Guo, ✉
| | - Xiujun Wang
- Zhengzhou Key Laboratory of Immunopharmacology of Traditional Chinese Veterinary Medicines, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
| | - Xuefei Wang
- Zhengzhou Key Laboratory of Immunopharmacology of Traditional Chinese Veterinary Medicines, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
| | - Yunxing Fu
- Zhengzhou Key Laboratory of Immunopharmacology of Traditional Chinese Veterinary Medicines, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
| | - Xianghui Li
- Zhengzhou Key Laboratory of Immunopharmacology of Traditional Chinese Veterinary Medicines, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
| | - Fuli Zhu
- Zhengzhou Key Laboratory of Immunopharmacology of Traditional Chinese Veterinary Medicines, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
| | - Guangyuan Hu
- Zhengzhou Key Laboratory of Immunopharmacology of Traditional Chinese Veterinary Medicines, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
| | - Xia Ma
- Zhengzhou Key Laboratory of Immunopharmacology of Traditional Chinese Veterinary Medicines, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China,Xia Ma, ✉
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24
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Wu C, Hu Q, Peng X, Luo J, Zhang G. Marine Fish Protein Peptide Regulating Potassium Oxonate-Induced Intestinal Dysfunction in Hyperuricemia Rats Helps Alleviate Kidney Inflammation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:320-330. [PMID: 36530149 DOI: 10.1021/acs.jafc.2c04017] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
The metabolic disease hyperuricemia (HUA) is characterized by a disturbance in purine metabolism. Peptides, such as marine fish-derived peptides, have previously been shown to be effective in alleviating HUA. In this study, HUA rats were induced by potassium oxonate with 100 mg/kg (L), 200 mg/kg (M), and 400 mg/kg (H) of marine fish protein peptide (MFPP). The results showed that MFPP could effectively reduce the serum uric acid (SUA) levels compared with the model group rats; kidney histopathology and the levels of inflammatory factors (TNF-α, IL-6, and IL-10) indicated that MFPP attenuated HUA-induced kidney inflammation. Meanwhile, MFPP restored the abundance of beneficial bacteria, including Lactobacillus, Blautia, Colidextribacter, and Intestinimonas. MFPP further repaired the intestinal barrier by recovering the expression of gene Ildr2 encoding the tricellular tight junction protein ILDR2 and the immune-related genes Ccr7 and Nr4a3 and also regulated the expression of Entpd8 and Cyp27b1 to restore kidney function and uric acid metabolism. MFPP was proved to have potential as a therapeutic strategy to be included in dietary intervention to relieve HUA.
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Affiliation(s)
- Changyu Wu
- Department of Food Science and Engineering, Jinan University, Guangzhou, 510632 Guangdong, China
| | - Qing Hu
- Department of Food Science and Engineering, Jinan University, Guangzhou, 510632 Guangdong, China
| | - Xichun Peng
- Department of Food Science and Engineering, Jinan University, Guangzhou, 510632 Guangdong, China
| | - Jianming Luo
- Department of Food Science and Engineering, Jinan University, Guangzhou, 510632 Guangdong, China
| | - Guangwen Zhang
- Department of Food Science and Engineering, Jinan University, Guangzhou, 510632 Guangdong, China
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25
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Chen N, Zhang J, Wang Z. Effects of middle-aged and elderly people's self-efficacy on health promotion behaviors: Mediating effects of sports participation. Front Psychol 2023; 13:889063. [PMID: 36687818 PMCID: PMC9845723 DOI: 10.3389/fpsyg.2022.889063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 11/28/2022] [Indexed: 01/06/2023] Open
Abstract
Objective This study explores the relationship between self-efficacy, sports participation, and health promotion behavior for middle-aged and elderly people. Therefore, it provides a theoretical reference for improving the quality of life for middle-aged and elderly adults and promoting a healthy lifestyle for the elderly. Methods A total of 591 (men: 36.2%; women: 63.8%; age: above 50 years) middle-aged and elderly adults from five cities of Henan Province were selected as the research objects by convenient sampling. The self-efficacy, sports participation, and health promotion behavior scales were used for the questionnaire survey. Amos24.0 was used to test the structural equation model, intermediary function test, and bootstrap analysis. Results: The self-efficacy of middle-aged and elderly people positively impacted health promotion behavior. The path coefficient was 0.439. Sports participation played a partial intermediary role between self-efficacy and health promotion behavior (χ 2/df = 1.785, root mean square error of approximation = 0.036, root mean square residual = 0.021, goodness-of-fit index = 0.967, comparative fit index = 0.976, Tucker-Lewis Index = 0.971) The proportion of intermediary effect was 26.34% (0.100, 0.225). Conclusion (1) Self-efficacy can significantly and positively affect health promotion behavior for middle-aged and elderly people; (2) sports participation plays a partial intermediary role between self-efficacy and health promotion behavior. From this point of view, we can enhance the self-efficacy of middle-aged and elderly people and improve their healthy life behavior by advancing sports participation. Thus, it provides theoretical support and practical guidance for promoting national health.
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Affiliation(s)
- Nan Chen
- School of Physical Education, Anyang Institute of Technology, Anyang, China
| | - Jia Zhang
- School of Physical Education, Chongqing University, Chongqing, China
| | - Zhiyong Wang
- Pain Department, Anyang City Third People’s Hospital, Anyang, China
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26
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Zhang Y, Wang T, Wan Z, Bai J, Xue Y, Dai R, Wang M, Peng Q. Alterations of the intestinal microbiota in age-related macular degeneration. Front Microbiol 2023; 14:1069325. [PMID: 37089564 PMCID: PMC10113553 DOI: 10.3389/fmicb.2023.1069325] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 03/09/2023] [Indexed: 04/25/2023] Open
Abstract
Purpose Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50. Recently, intestinal microbiota has been reported to be involved in the pathogenesis of ocular diseases. The purpose of this study was to discover more about the involvement of the intestinal microbiota in AMD patients. Methods Fecal samples from 30 patients with AMD (AMD group) and 17 age- and sex-matched healthy controls (control group) without any fundus disease were collected. DNA extraction, PCR amplification, and 16S rRNA gene sequencing of the samples were performed to identify intestinal microbial alterations. Further, we used BugBase for phenotypic prediction and PICRUSt2 for KEGG Orthology (KO) as well as metabolic feature prediction. Results The intestinal microbiota was found to be significantly altered in the AMD group. The AMD group had a significantly lower level of Firmicutes and relatively higher levels of Proteobacteria and Bacteroidota compared to those in the control group. At the genus level, the AMD patient group showed a considerably higher proportion of Escherichia-Shigella and lower proportions of Blautia and Anaerostipes compared with those in the control group. Phenotypic prediction revealed obvious differences in the four phenotypes between the two groups. PICRUSt2 analysis revealed KOs and pathways associated with altered intestinal microbiota. The abundance of the top eight KOs in the AMD group was higher than that in the control group. These KOs were mainly involved in lipopolysaccharide biosynthesis. Conclusion The findings of this study indicated that AMD patients had different gut microbiota compared with healthy controls, and that AMD pathophysiology might be linked to changes in gut-related metabolic pathways. Therefore, intestinal microbiota might serve as non-invasive indicators for AMD clinical diagnosis and possibly also as AMD treatment targets.
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Affiliation(s)
- Yuanyuan Zhang
- Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Tianyu Wang
- Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhongqi Wan
- Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jianhao Bai
- Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yawen Xue
- Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Rushun Dai
- Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
- *Correspondence: Rushun Dai,
| | - Minli Wang
- Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Minli Wang,
| | - Qing Peng
- Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Qing Peng,
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27
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Xu XJ, Lang JD, Yang J, Long B, Liu XD, Zeng XF, Tian G, You X. Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study. Front Immunol 2023; 14:1100816. [PMID: 36875075 PMCID: PMC9975759 DOI: 10.3389/fimmu.2023.1100816] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 02/06/2023] [Indexed: 02/17/2023] Open
Abstract
Background Autism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has been hypothesized to involve in the pathophysiology of a subtype of ASD. Methods A cohort of 105 ASD children were recruited and grouped based on IFN-γ levels derived from ex vivo stimulated γδT cells. Fecal samples were collected and analyzed with a metagenomic approach. Comparison of autistic symptoms and gut microbiota composition was made between subgroups. Enriched KEGG orthologues markers and pathogen-host interactions based on metagenome were also analyzed to reveal the differences in functional features. Results The autistic behavioral symptoms were more severe for children in the IFN-γ-high group, especially in the body and object use, social and self-help, and expressive language performance domains. LEfSe analysis of gut microbiota revealed an overrepresentation of Selenomonadales, Negatiyicutes, Veillonellaceae and Verrucomicrobiaceae and underrepresentation of Bacteroides xylanisolvens and Bifidobacterium longum in children with higher IFN-γ level. Decreased metabolism function of carbohydrate, amino acid and lipid in gut microbiota were found in the IFN-γ-high group. Additional functional profiles analyses revealed significant differences in the abundances of genes encoding carbohydrate-active enzymes between the two groups. And enriched phenotypes related to infection and gastroenteritis and underrepresentation of one gut-brain module associated with histamine degradation were also found in the IFN-γ-High group. Results of multivariate analyses revealed relatively good separation between the two groups. Conclusions Levels of IFN-γ derived from γδT cell could serve as one of the potential candidate biomarkers to subtype ASD individuals to reduce the heterogeneity associated with ASD and produce subgroups which are more likely to share a more similar phenotype and etiology. A better understanding of the associations among immune function, gut microbiota composition and metabolism abnormalities in ASD would facilitate the development of individualized biomedical treatment for this complex neurodevelopmental disorder.
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Affiliation(s)
- Xin-Jie Xu
- Medical Science Research Center, Research Center for Translational Medicine, Department of Scientific Research, Peking Union Medical College Hospital, Beijing, China.,Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ji-Dong Lang
- Precision Medicine Center, Geneis Beijing Co., Ltd., Beijing, China
| | - Jun Yang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bo Long
- Medical Science Research Center, Research Center for Translational Medicine, Department of Scientific Research, Peking Union Medical College Hospital, Beijing, China
| | - Xu-Dong Liu
- Medical Science Research Center, Research Center for Translational Medicine, Department of Scientific Research, Peking Union Medical College Hospital, Beijing, China
| | - Xiao-Feng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Geng Tian
- Precision Medicine Center, Geneis Beijing Co., Ltd., Beijing, China
| | - Xin You
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.,Autism Special Fund, Peking Union Medical Foundation, Beijing, China
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28
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Zhang Y, Liu Y, Ma H, Sun M, Wang X, Jin S, Yuan X. Insufficient or excessive dietary carbohydrates affect gut health through change in gut microbiota and regulation of gene expression of gut epithelial cells in grass carp (Ctenopharyngodon idella). FISH & SHELLFISH IMMUNOLOGY 2023; 132:108442. [PMID: 36410648 DOI: 10.1016/j.fsi.2022.11.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 11/11/2022] [Accepted: 11/17/2022] [Indexed: 06/16/2023]
Abstract
Dietary carbohydrate levels can affect gut health, but the roles played by gut microbiota and gut epithelial cells, and their interactions remain unclear. In this experiment, we investigated gut health, gut microbiota, and the gene expression profiles of gut epithelial cells in grass carp consuming diets with different carbohydrate levels. Compared to the moderate-carbohydrate diet, low-carbohydrate diet significantly increased the relative abundance of pathogenic bacteria (Ralstonia and Elizabethkingia) and decreased the abundance of metabolism in cofactors and vitamins, implying a dysregulated gut microbiota and compromised metabolic function. Moreover, low-carbohydrate diet inhibited the expression levels of key genes in autophagy-related pathways in gut epithelial cells, which might directly lead to reduced clearance of defective organelles and pathogenic microorganisms. These aforementioned factors may be responsible for the imperfect organization of the intestinal tract. High-carbohydrate diet also significantly increased the abundance of pathogenic bacteria (Flavobacterium), which directly contributed to a decrease in the abundance of immune system of the microbiota. Furthermore, the active pathways of staphylococcus aureus infection and complement and coagulation cascades, as well as the inhibition of the glutathione metabolism pathway were observed. Above results implied that high-carbohydrate diet might ultimately cause severe gut damage by affecting immune function of microbiota, mentioned immune-related pathways, and the antioxidant capacity. Finally, the correlation network diagram revealed strong correlations of the differentially immune-related gene major histocompatibility complex class I antigen (MR1) with Enhydrobacter and Ruminococcus_gnavus_group in low-carbohydrate diet group, and Arenimonas in high-carbohydrate diet group, respectively, suggesting that MR1 might be a central target for immune responses in gut epithelial cells induced by gut microbiota at different levels of dietary carbohydrate. All these results provided insight in the development of antagonistic probiotics and target genes to improve the utilization of carbohydrate.
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Affiliation(s)
- Yanpeng Zhang
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Yucheng Liu
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Huan Ma
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Manjie Sun
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Xin Wang
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Shengzhen Jin
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China
| | - Xiaochen Yuan
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, Anhui, China.
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29
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Wang P, Zhang X, Zheng X, Gao J, Shang M, Xu J, Liang H. Folic Acid Protects against Hyperuricemia in C57BL/6J Mice via Ameliorating Gut-Kidney Axis Dysfunction. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:15787-15803. [PMID: 36473110 DOI: 10.1021/acs.jafc.2c06297] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Emerging lines of research evidence point to a vital role of gut-kidney axis in the development of hyperuricemia (HUA), which has been identified as an increasing burden worldwide due to the high prevalence. The involved crosstalk which links the metabolic and immune-related pathways is mainly responsible for maintaining the axial homeostasis of uric acid (UA) metabolism. Nowadays, the urate-lowering drugs only aim to treat acute gouty arthritis as a result of their controversial clinical application in HUA. In this study, we established the HUA model of C57BL/6J mice to evaluate the effectiveness of folic acid on UA metabolism and further explored the underlying mechanisms. Folic acid attenuated the kidney tissue injury and excretion dysfunction, as well as the typical fibrosis in HUA mice. Molecular docking results also revealed the structure-activity relationship of the folic acid metabolic unit and the UA transporters GLUT9 and URAT1, implying the potential interaction. Also, folic acid alleviated HUA-induced Th17/Treg imbalance and intestinal tissue damage and inhibited the active state of the TLR4/NF-κB signaling pathway, which is closely associated with the circulating LPS level caused by the impaired intestinal permeability. Furthermore, the changes of intestinal microecology induced by HUA were restored by folic acid, including the alteration in the structure and species composition of the gut microbiome community, and metabolite short-chain fatty acids. Collectively, this study revealed that folic acid intervention exerted improving effects on HUA by ameliorating gut-kidney axis dysfunction.
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Affiliation(s)
- Peng Wang
- Department of Nutrition and Food Hygiene, College of Public Health, Qingdao University, Ning Xia Road 308, Qingdao 266071, China
| | - Xiaoqi Zhang
- Department of Nutrition and Food Hygiene, College of Public Health, Qingdao University, Ning Xia Road 308, Qingdao 266071, China
| | - Xian Zheng
- Department of Nutrition and Food Hygiene, College of Public Health, Qingdao University, Ning Xia Road 308, Qingdao 266071, China
| | - Jingru Gao
- Department of Nutrition and Food Hygiene, College of Public Health, Qingdao University, Ning Xia Road 308, Qingdao 266071, China
| | - Mengfei Shang
- Department of Nutrition and Food Hygiene, College of Public Health, Qingdao University, Ning Xia Road 308, Qingdao 266071, China
| | - Jinghan Xu
- Department of Nutrition and Food Hygiene, College of Public Health, Qingdao University, Ning Xia Road 308, Qingdao 266071, China
| | - Hui Liang
- Department of Nutrition and Food Hygiene, College of Public Health, Qingdao University, Ning Xia Road 308, Qingdao 266071, China
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Shi J, Qiu H, Xu Q, Ma Y, Ye T, Kuang Z, Qu N, Kan C, Hou N, Han F, Sun X. Integrated multi-omics analyses reveal effects of empagliflozin on intestinal homeostasis in high-fat-diet mice. iScience 2022; 26:105816. [PMID: 36636340 PMCID: PMC9830204 DOI: 10.1016/j.isci.2022.105816] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/25/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
Obesity has become a global epidemic, associated with several chronic complications. The intestinal microbiome is a critical regulator of metabolic homeostasis and obesity. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has putative anti-obesity effects. In this study, we used multi-omics analysis to determine whether empagliflozin regulates metabolism in an obese host through the intestinal microbiota. Compared with obese mice, the empagliflozin-treated mice had a higher species diversity of gut microbiota, characterized by a reduction in the Firmicutes/Bacteroides ratio. Metabolomic analysis unambiguously identified 1,065 small molecules with empagliflozin affecting metabolites mainly enriched in amino acid metabolism, such as tryptophan metabolism. RNA sequencing results showed that immunoglobulin A and peroxisome proliferator-activated receptor signaling pathways in the intestinal immune network were activated after empagliflozin treatment. This integrative analysis highlighted that empagliflozin maintains intestinal homeostasis by modulating gut microbiota diversity and tryptophan metabolism. This will inform the development of therapies for obesity based on host-microbe interactions.
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Affiliation(s)
- Junfeng Shi
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Hongyan Qiu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Qian Xu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Yuting Ma
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Tongtong Ye
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Zengguang Kuang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Na Qu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Chengxia Kan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Ningning Hou
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Fang Han
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China,Department of Pathology, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Corresponding author
| | - Xiaodong Sun
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, Shandong 261031, China,Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China,Corresponding author
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Fat Quality Impacts the Effect of a High-Fat Diet on the Fatty Acid Profile, Life History Traits and Gene Expression in Drosophila melanogaster. Cells 2022; 11:cells11244043. [PMID: 36552807 PMCID: PMC9776686 DOI: 10.3390/cells11244043] [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: 11/15/2022] [Revised: 12/08/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Feeding a high-fat diet (HFD) has been shown to alter phenotypic and metabolic parameters in Drosophila melanogaster. However, the impact of fat quantity and quality remains uncertain. We first used butterfat (BF) as an example to investigate the effects of increasing dietary fat content (3-12%) on male and female fruit flies. Although body weight and body composition were not altered by any BF concentration, health parameters, such as lifespan, fecundity and larval development, were negatively affected in a dose-dependent manner. When fruit flies were fed various 12% HFDs (BF, sunflower oil, olive oil, linseed oil, fish oil), their fatty acid profiles shifted according to the dietary fat qualities. Moreover, fat quality was found to determine the effect size of the response to an HFD for traits, such as lifespan, climbing activity, or fertility. Consistently, we also found a highly fat quality-specific transcriptional response to three exemplary HFD qualities with a small overlap of only 30 differentially expressed genes associated with the immune/stress response and fatty acid metabolism. In conclusion, our data indicate that not only the fat content but also the fat quality is a crucial factor in terms of life-history traits when applying an HFD in D. melanogaster.
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Ginsenoside compound K increases glucagon-like peptide-1 release and L-cell abundance in db/db mice through TGR5/YAP signaling. Int Immunopharmacol 2022; 113:109405. [DOI: 10.1016/j.intimp.2022.109405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 10/11/2022] [Accepted: 10/28/2022] [Indexed: 11/11/2022]
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Li J, Lv JL, Cao XY, Zhang HP, Tan YJ, Chu T, Zhao LL, Liu Z, Ren YS. Gut microbiota dysbiosis as an inflammaging condition that regulates obesity-related retinopathy and nephropathy. Front Microbiol 2022; 13:1040846. [PMID: 36406423 PMCID: PMC9666733 DOI: 10.3389/fmicb.2022.1040846] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 10/17/2022] [Indexed: 01/21/2023] Open
Abstract
Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage. Epidemiological data demonstrated that the high morbidity of T2DM occurs as a result of obesity and gradually develops into serious complications. To date, the mechanisms that underlie this observation are still ill-defined. In view of the effect of obesity on the gut microflora, Leprdb/db mice underwent antibiotic treatment and microbiota transplants to modify the gut microbiome to investigate whether microbes are involved in the development of diabetic nephropathy (DN) and/or diabetic retinopathy (DR). The mouse feces were collected for bacterial 16S ribosomal RNA gene sequencing. Cytokines including TNF-α, TGF-β1, IFN-γ, IL-1β, IL-6, IL-17A, IL-10, and VEGFA were detected by enzyme-linked immunosorbent assay (ELISA), flow cytometry, real-time PCR and immunofluorescent assay. Eyes and kidney were collected for histopathological assay. Intestinal permeability was also detected using Evans Blue. The results showed that obesity influenced metabolic variables (including fast/fed glucose, insulin, and triglyceride), retinopathy and nephropathy, and the gut microbiota. Obesity mainly reduced the ratio of Bacteroidetes/Firmicutes and influenced relative abundance of Proteobacteria, Actinobacteria, and Spirochetes. Obesity also increased intestinal permeability, metabolic endotoxemia, cytokines, and VEGFA. Microbiota transplants confirm that obesity aggravates retinopathy and nephropathy through the gut microbiota. These findings suggest that obesity exacerbates retinopathy and nephropathy by inducing gut microbiota dysbiosis, which further enhanced intestinal permeability and chronic low-grade inflammation.
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Affiliation(s)
- Jie Li
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, Binzhou Medical University, Yantai, China
| | - Jun-lin Lv
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, Binzhou Medical University, Yantai, China
| | - Xin-yue Cao
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, Binzhou Medical University, Yantai, China
| | - Hai-ping Zhang
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, China
| | - Yu-jun Tan
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, Binzhou Medical University, Yantai, China
| | - Ting Chu
- School of Life Sciences, Jiangsu Normal University, Xuzhou, China
| | - Li-li Zhao
- State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, China
| | - Zhong Liu
- State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, China,*Correspondence: Zhong Liu,
| | - Yu-shan Ren
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, Binzhou Medical University, Yantai, China,Yu-shan Ren,
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Chen K, Gao Z, Ding Q, Tang C, Zhang H, Zhai T, Xie W, Jin Z, Zhao L, Liu W. Effect of natural polyphenols in Chinese herbal medicine on obesity and diabetes: Interactions among gut microbiota, metabolism, and immunity. Front Nutr 2022; 9:962720. [PMID: 36386943 PMCID: PMC9651142 DOI: 10.3389/fnut.2022.962720] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 09/20/2022] [Indexed: 08/30/2023] Open
Abstract
With global prevalence, metabolic diseases, represented by obesity and type 2 diabetes mellitus (T2DM), have a huge burden on human health and medical expenses. It is estimated that obese population has doubled in recent 40 years, and population with diabetes will increase 1.5 times in next 25 years, which has inspired the pursuit of economical and effective prevention and treatment methods. Natural polyphenols are emerging as a class of natural bioactive compounds with potential beneficial effects on the alleviation of obesity and T2DM. In this review, we investigated the network interaction mechanism of "gut microbial disturbance, metabolic disorder, and immune imbalance" in both obesity and T2DM and systemically summarized their multiple targets in the treatment of obesity and T2DM, including enrichment of the beneficial gut microbiota (genera Bifidobacterium, Akkermansia, and Lactobacillus) and upregulation of the levels of gut microbiota-derived metabolites [short-chain fatty acids (SCFAs)] and bile acids (BAs). Moreover, we explored their effect on host glucolipid metabolism, the AMPK pathway, and immune modulation via the inhibition of pro-inflammatory immune cells (M1-like Mϕs, Th1, and Th17 cells); proliferation, recruitment, differentiation, and function; and related cytokines (TNF-α, IL-1β, IL-6, IL-17, and MCP-1). We hope to provide evidence to promote the clinical application of natural polyphenols in the management of obesity and T2DM.
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Affiliation(s)
- Keyu Chen
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Zezheng Gao
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiyou Ding
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Cheng Tang
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Haiyu Zhang
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Tiangang Zhai
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Weinan Xie
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Zishan Jin
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Linhua Zhao
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wenke Liu
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Dong Y, Wang P, Yang X, Chen M, Li J. Potential of gut microbiota for lipopolysaccharide biosynthesis in European women with type 2 diabetes based on metagenome. Front Cell Dev Biol 2022; 10:1027413. [PMID: 36303603 PMCID: PMC9592851 DOI: 10.3389/fcell.2022.1027413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 09/27/2022] [Indexed: 11/16/2022] Open
Abstract
The abnormal accumulation of lipopolysaccharide (LPS) plays a crucial role in promoting type 2 diabetes (T2D). However, the capability of the gut microbiota to produce LPS in patients with T2D is still unclear, and evidence characterizing the patterns of gut microbiota with LPS productivity remains rare. This study aimed to uncover the profiles of LPS-biosynthesis-related enzymes and pathways, and explore the potential of LPS-producing gut microbiota in T2D. The gut metagenomic sequencing data from a European female cohort with normal glucose tolerance or untreated T2D were analyzed in this study. The sequence search revealed that the relative abundance of the critical enzymes responsible for LPS biosynthesis was significantly high in patients with T2D, especially for N-acetylglucosamine deacetylase, 3-deoxy-D-manno-octulosonic-acid transferase, and lauroyl-Kdo2-lipid IVA myristoyltransferase. The functional analysis indicated that a majority of pathways involved in LPS biosynthesis were augmented in patients with T2D. A total of 1,173 species from 335 genera containing the gene sequences of LPS enzymes, including LpxA/B/C/D/H/K/L/M and/or WaaA, coexisted in controls and patients with T2D. Critical taxonomies with discriminative fecal abundance between groups were revealed, which exhibited different associations with enzymes. Moreover, the identified gut microbial markers had correlations with LPS enzymes and were subsequently associated with microbial pathways. The present findings delineated the potential capability of gut microbiota toward LPS biosynthesis in European women and highlighted a gut microbiota−based mechanistic link between the disturbance in LPS biosynthesis and T2D. The restoration of LPS levels through gut microbiota manipulation might offer potential approaches for preventing and treating T2D.
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Yang W, Jannatun N, Zeng Y, Liu T, Zhang G, Chen C, Li Y. Impacts of microplastics on immunity. FRONTIERS IN TOXICOLOGY 2022; 4:956885. [PMID: 36238600 PMCID: PMC9552327 DOI: 10.3389/ftox.2022.956885] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 08/24/2022] [Indexed: 11/13/2022] Open
Abstract
Most disposable plastic products are degraded slowly in the natural environment and continually turned to microplastics (MPs) and nanoplastics (NPs), posing additional environmental hazards. The toxicological assessment of MPs for marine organisms and mammals has been reported. Thus, there is an urgent need to be aware of the harm of MPs to the human immune system and more studies about immunological assessments. This review focuses on how MPs are produced and how they may interact with the environment and our body, particularly their immune responses and immunotoxicity. MPs can be taken up by cells, thus disrupting the intracellular signaling pathways, altering the immune homeostasis and finally causing damage to tissues and organs. The generation of reactive oxygen species is the mainly toxicological mechanisms after MP exposure, which may further induce the production of danger-associated molecular patterns (DAMPs) and associate with the processes of toll-like receptors (TLRs) disruption, cytokine production, and inflammatory responses in immune cells. MPs effectively interact with cell membranes or intracellular proteins to form a protein-corona, and combine with external pollutants, chemicals, and pathogens to induce greater toxicity and strong adverse effects. A comprehensive research on the immunotoxicity effects and mechanisms of MPs, including various chemical compositions, shapes, sizes, combined exposure and concentrations, is worth to be studied. Therefore, it is urgently needed to further elucidate the immunological hazards and risks of humans that exposed to MPs.
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Affiliation(s)
- Wenjie Yang
- Laboratory of Immunology and Nanomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Nahar Jannatun
- Laboratory of Immunology and Nanomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Yanqiao Zeng
- Laboratory of Immunology and Nanomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Tinghao Liu
- Laboratory of Immunology and Nanomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Guofang Zhang
- Laboratory of Immunology and Nanomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Chunying Chen
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nano Safety, National Centre for Nanoscience and Technology of China, Chinese Academy of Sciences, Beijing, China
- GBA Research Innovation Institute for Nanotechnology, Guangzhou, Guangdong, China
| | - Yang Li
- Laboratory of Immunology and Nanomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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Liu K, Zou J, Fan H, Hu H, You Z. Causal effects of gut microbiota on diabetic retinopathy: A Mendelian randomization study. Front Immunol 2022; 13:930318. [PMID: 36159877 PMCID: PMC9496187 DOI: 10.3389/fimmu.2022.930318] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 08/18/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundPrevious researches have implicated a vital association between gut microbiota (GM) and diabetic retinopathy (DR) based on the association of the “gut-retina” axis. But their causal relationship has not been elucidated.MethodsInstrumental variables of 211 GM taxa were obtained from genome wide association study (GWAS), and Mendelian randomization study was carried out to estimate their effects on DR risk from FinnGen GWAS (14,584 DR cases and 202,082 controls). Inverse variance weighted (IVW) is the main method to analyze causality, and MR results are verified by several sensitive analyses.ResultsAs for 211 GM taxa, IVW results confirmed that family-Christensenellaceae (P = 1.36×10-2) and family-Peptococcaceae (P = 3.13×10-2) were protective factors for DR. Genus-Ruminococcaceae_UCG_011 (P = 4.83×10-3), genus-Eubacterium_rectale_group (P = 3.44×10-2) and genus-Adlercreutzia (P = 4.82×10-2) were correlated with the risk of DR. At the phylum, class and order levels, we found no GM taxa that were causally related to DR (P>0.05). Heterogeneity (P>0.05) and pleiotropy (P>0.05) analysis confirmed the robustness of MR results.ConclusionWe confirmed that there was a potential causal relationship between some GM taxa and DR, which highlights the association of the “gut-retina” axis and offered new insights into the GM-mediated mechanism of DR. Further explorations of their association are required and will lead to find new biomarkers for targeted prevention strategies of DR.
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Affiliation(s)
- Kangcheng Liu
- Jiangxi Province Division of National Clinical Research Center for Ocular Diseases, Jiangxi Clinical Research Center for Ophthalmic Disease, Jiangxi Research Institute of Ophthalmology and Visual Science, Affiliated Eye Hospital of Nanchang University, Nanchang, China
| | - Jing Zou
- Hunan Key Laboratory of Ophthalmology, Eye Center of Xiangya Hospital, Central South University, Changsha, China
| | - Huimin Fan
- Jiangxi Province Division of National Clinical Research Center for Ocular Diseases, Jiangxi Clinical Research Center for Ophthalmic Disease, Jiangxi Research Institute of Ophthalmology and Visual Science, Affiliated Eye Hospital of Nanchang University, Nanchang, China
| | - Hanying Hu
- Jiangxi Province Division of National Clinical Research Center for Ocular Diseases, Jiangxi Clinical Research Center for Ophthalmic Disease, Jiangxi Research Institute of Ophthalmology and Visual Science, Affiliated Eye Hospital of Nanchang University, Nanchang, China
| | - Zhipeng You
- Jiangxi Province Division of National Clinical Research Center for Ocular Diseases, Jiangxi Clinical Research Center for Ophthalmic Disease, Jiangxi Research Institute of Ophthalmology and Visual Science, Affiliated Eye Hospital of Nanchang University, Nanchang, China
- *Correspondence: Zhipeng You,
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Dong J, Ping L, Cao T, Sun L, Liu D, Wang S, Huo G, Li B. Immunomodulatory effects of the Bifidobacterium longum BL-10 on lipopolysaccharide-induced intestinal mucosal immune injury. Front Immunol 2022; 13:947755. [PMID: 36091059 PMCID: PMC9450040 DOI: 10.3389/fimmu.2022.947755] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/27/2022] [Indexed: 12/12/2022] Open
Abstract
The intestine is the largest digestive and immune organ in the human body, with an intact intestinal mucosal barrier. Bifidobacterium longum is the specific gut commensals colonized in the human gut for boosting intestinal immunity to defend against intestinal mucosal immune injury. In the LPS-induced intestinal injury model, the Bifidobacterium longum BL-10 was suggested to boost the intestinal immune. Detailly, compared with the LPS-induced mice, the BL10 group significantly reduced intestine (jejunum, ileum, and colon) tissue injury, pro-inflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-6, IL-17, IL-22, and IL-12) levels and myeloperoxidase activities. Moreover, the B. longum BL-10 significantly increased the number of immunocytes (CD4+ T cells, IgA plasma cells) and the expression of tight junction protein (Claudin1 and Occludin). B. longum BL-10 regulated the body's immune function by regulating the Th1/Th2 and Th17/Treg balance, which showed a greater impact on the Th1/Th2 balance. Moreover, the results also showed that B. longum BL-10 significantly down-regulated the intestinal protein expression of TLR4, p-IκB, and NF-κB p65. The B. longum BL-10 increased the relative abundance of the genera, including Lachnospiraceae_NK4A136_group and Clostridia_UCG-014, which were related to declining the levels of intestinal injury. Overall, these results indicated that the B. longum BL-10 had great functionality in reducing LPS-induced intestinal mucosal immune injury.
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Affiliation(s)
| | | | | | | | | | - Song Wang
- Food College, Northeast Agricultural University, Harbin, China
| | - Guicheng Huo
- Food College, Northeast Agricultural University, Harbin, China
| | - Bailiang Li
- Food College, Northeast Agricultural University, Harbin, China
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Kidney Bean Fermented Broth Alleviates Hyperlipidemic by Regulating Serum Metabolites and Gut Microbiota Composition. Nutrients 2022; 14:nu14153202. [PMID: 35956378 PMCID: PMC9370468 DOI: 10.3390/nu14153202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 07/29/2022] [Accepted: 07/30/2022] [Indexed: 11/26/2022] Open
Abstract
Hyperlipidemia with fat accumulation and weight gain causes metabolic diseases and endangers human body health easily which is accompanied by metabolic abnormalities and intestinal flora disorders. In this study, the kidney bean fermented broth (KBF) was used in rats that were fed a high-fat diet to induce hyperlipidemia in order to subsequently analyse the serum metabolomics and gut microbiota modulatoration. The results show that the contents of the total polyphenols and total flavonoids in the KBF were up three and one times, while energy and carbohydrates decreased. In the HFD-induced hyperlipidemic model, body weight, organ weight, and the level of blood lipids (ALT, AST, TG, TC) were lower in rats treated with KBF than in the controls. Metabonomics indicate that there were significant differences in serum metabolomics between the KBF and the HFD. KBF could significantly improve the glycerophospholipids, taurine, and hypotaurine metabolism and amino acid metabolism of hyperlipidemic rats and then improve the symptoms of hypersterol and fat accumulation in rats. The relative abundance of beneficial bacteria increased while pathogenic bacteria decreased after the intervention of KBF. KBF ameliorates dyslipidemia of HFD-induced hyperlipidemic via modulating the blood metabolism and the intestinal microbiota. Collectively, these findings suggest that KBF could be developed as a functional food for anti-hyperlipidemia.
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Xiao L, Sun Y, Tsao R. Paradigm Shift in Phytochemicals Research: Evolution from Antioxidant Capacity to Anti-Inflammatory Effect and to Roles in Gut Health and Metabolic Syndrome. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:8551-8568. [PMID: 35793510 DOI: 10.1021/acs.jafc.2c02326] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Food bioactive components, particularly phytochemicals with antioxidant capacity, have been extensively studied over the past two decades. However, as new analytical and molecular biological tools advance, antioxidants related research has undergone significant paradigm shifts. This review is a high-level overview of the evolution of phytochemical antioxidants research. Early research used chemical models to assess the antioxidant capacity of different phytochemicals, which provided important information about the health potential, but the results were overused and misinterpreted despite the lack of biological relevance (Antioxidants v1.0). This led to findings in the anti-inflammatory properties and modulatory effects of cell signaling of phytochemicals (Antioxidants v2.0). Recent advances in the role of diet in modulating gut microbiota have suggested a new phase of food bioactives research along the phytochemicals-gut microbiota-intestinal metabolites-low-grade inflammation-metabolic syndrome axis (Antioxidants v3.0). Polyphenols and carotenoids were discussed in-depth, and future research directions were also provided.
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Affiliation(s)
- Lihua Xiao
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, Jiangxi, China
| | - Yong Sun
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, Jiangxi, China
| | - Rong Tsao
- Guelph Research and Development Centre, Agricultural and Agri-Food Canada, 93 Stone Road West, Guelph, ON N1G 5C9, Canada
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Kang CQ, Meng QY, Dang W, Shao YJ, Lu HL. Effects of chronic exposure to the fungicide vinclozolin on gut microbiota community in an aquatic turtle. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2022; 239:113621. [PMID: 35569300 DOI: 10.1016/j.ecoenv.2022.113621] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/01/2022] [Accepted: 05/07/2022] [Indexed: 06/15/2023]
Abstract
Environmental issues associated with the widespread use of agricultural chemicals are being seriously concerned. Of them, toxicological impacts of fungicides in aquatic organisms are often overlooked. Here, soft-shelled turtle (Pelodiscus sinensis) hatchlings were exposed to different concentrations of vinclozolin (0, 5, 50, 500 and 5000 μg/L) for 60 days to investigate the impact of fungicide exposure on their gut microbial composition and diversity. Vinclozolin exposure significantly affected the composition of the gut microbiota in hatchling turtles. Unexpectedly, gut bacterial diversity and richness of vinclozolin-exposed turtles (but not for the 5000 μg/L-exposed group) were relatively higher than control ones. At the phylum level, the abundance of Firmicutes was decreased, while that of Proteobacteria was increased in high-concentration groups. At the genus level, some bacterial genera including Cellulosilyticum, Romboutsia and Clostridium_sensu_stricto, were significantly changed after vinclozolin exposure; and some uniquely observed in high-concentration groups. Gene function predictions showed that genes related to amino acid metabolism were less abundant, while those related to energy metabolism more abundant in high-concentration groups. The prevalence of some pathogens inevitably affected gut health status of vinclozolin-exposed turtles. Such gut microbiota dysbiosis might be potentially linked with hepatic metabolite changes induced by vinclozolin exposure.
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Affiliation(s)
- Chun-Quan Kang
- Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China
| | - Qin-Yuan Meng
- Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China
| | - Wei Dang
- Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China
| | - Yong-Jian Shao
- Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China
| | - Hong-Liang Lu
- Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China.
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Milenkovic D, Capel F, Combaret L, Comte B, Dardevet D, Evrard B, Guillet C, Monfoulet LE, Pinel A, Polakof S, Pujos-Guillot E, Rémond D, Wittrant Y, Savary-Auzeloux I. Targeting the gut to prevent and counteract metabolic disorders and pathologies during aging. Crit Rev Food Sci Nutr 2022; 63:11185-11210. [PMID: 35730212 DOI: 10.1080/10408398.2022.2089870] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Impairment of gut function is one of the explanatory mechanisms of health status decline in elderly population. These impairments involve a decline in gut digestive physiology, metabolism and immune status, and associated to that, changes in composition and function of the microbiota it harbors. Continuous deteriorations are generally associated with the development of systemic dysregulations and ultimately pathologies that can worsen the initial health status of individuals. All these alterations observed at the gut level can then constitute a wide range of potential targets for development of nutritional strategies that can impact gut tissue or associated microbiota pattern. This can be key, in a preventive manner, to limit gut functionality decline, or in a curative way to help maintaining optimum nutrients bioavailability in a context on increased requirements, as frequently observed in pathological situations. The aim of this review is to give an overview on the alterations that can occur in the gut during aging and lead to the development of altered function in other tissues and organs, ultimately leading to the development of pathologies. Subsequently is discussed how nutritional strategies that target gut tissue and gut microbiota can help to avoid or delay the occurrence of aging-related pathologies.
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Affiliation(s)
- Dragan Milenkovic
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Frédéric Capel
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Lydie Combaret
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Blandine Comte
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Dominique Dardevet
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Bertrand Evrard
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Christelle Guillet
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | | | - Alexandre Pinel
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Sergio Polakof
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Estelle Pujos-Guillot
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Didier Rémond
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
| | - Yohann Wittrant
- Human Nutrition Unit, UMR1019, University Clermont Auvergne, INRAE, Clermont-Ferrand, France
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Coccurello R, Marrone MC, Maccarrone M. The Endocannabinoids-Microbiota Partnership in Gut-Brain Axis Homeostasis: Implications for Autism Spectrum Disorders. Front Pharmacol 2022; 13:869606. [PMID: 35721203 PMCID: PMC9204215 DOI: 10.3389/fphar.2022.869606] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 04/20/2022] [Indexed: 11/13/2022] Open
Abstract
The latest years have witnessed a growing interest towards the relationship between neuropsychiatric disease in children with autism spectrum disorders (ASD) and severe alterations in gut microbiota composition. In parallel, an increasing literature has focused the attention towards the association between derangement of the endocannabinoids machinery and some mechanisms and symptoms identified in ASD pathophysiology, such as alteration of neural development, immune system dysfunction, defective social interaction and stereotypic behavior. In this narrative review, we put together the vast ground of endocannabinoids and their partnership with gut microbiota, pursuing the hypothesis that the crosstalk between these two complex homeostatic systems (bioactive lipid mediators, receptors, biosynthetic and hydrolytic enzymes and the entire bacterial gut ecosystem, signaling molecules, metabolites and short chain fatty acids) may disclose new ideas and functional connections for the development of synergic treatments combining “gut-therapy,” nutritional intervention and pharmacological approaches. The two separate domains of the literature have been examined looking for all the plausible (and so far known) overlapping points, describing the mutual changes induced by acting either on the endocannabinoid system or on gut bacteria population and their relevance for the understanding of ASD pathophysiology. Both human pathology and symptoms relief in ASD subjects, as well as multiple ASD-like animal models, have been taken into consideration in order to provide evidence of the relevance of the endocannabinoids-microbiota crosstalk in this major neurodevelopmental disorder.
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Affiliation(s)
- Roberto Coccurello
- Institute for Complex Systems (ISC), National Council of Research (CNR), Rome, Italy
- European Center for Brain Research/Santa Lucia Foundation IRCCS, Rome, Italy
- *Correspondence: Roberto Coccurello, ; Mauro Maccarrone,
| | - Maria Cristina Marrone
- Ministry of University and Research, Mission Unity for Recovery and Resilience Plan, Rome, Italy
| | - Mauro Maccarrone
- European Center for Brain Research/Santa Lucia Foundation IRCCS, Rome, Italy
- Department of Biotechnological and Applied Clinical and Sciences, University of L’Aquila, L’Aquila, Italy
- *Correspondence: Roberto Coccurello, ; Mauro Maccarrone,
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44
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Eco-Evolutionary Dynamics of the Human-Gut Microbiota Symbiosis in a Changing Nutritional Environment. Evol Biol 2022. [DOI: 10.1007/s11692-022-09569-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
AbstractThe operational harmony between living beings and their circumstances, their ever-changing environment, is a constitutive condition of their existence. Nutrition and symbiosis are two essential aspects of this harmony. Disruption of the symbiosis between host and gut microbiota, the so-called dysbiosis, as well as the inadequate diet from which it results, contribute to the etiology of immunometabolic disorders. Research into the development of these diseases is highly influenced by our understanding of the evolutionary roots of metabolic functioning, thereby considering that chronic non-communicable diseases arise from an evolutionary mismatch. However, the lens has been mostly directed toward energy availability and metabolism, but away from our closest environmental factor, the gut microbiota. Thus, this paper proposes a narrative thread that places symbiosis in an evolutionary perspective, expanding the traditional framework of humans’ adaptation to their food environment.
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Tian F, Huang S, Xu W, Chen L, Su J, Ni H, Feng X, Chen J, Wang X, Huang Q. Compound K attenuates hyperglycemia by enhancing glucagon-like peptide-1 secretion through activating TGR5 via the remodeling of gut microbiota and bile acid metabolism. J Ginseng Res 2022; 46:780-789. [PMID: 36312739 PMCID: PMC9597441 DOI: 10.1016/j.jgr.2022.03.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 02/25/2022] [Accepted: 03/29/2022] [Indexed: 01/06/2023] Open
Abstract
Background Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.
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Affiliation(s)
- Fengyuan Tian
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Shuo Huang
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Wangda Xu
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Lan Chen
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jianming Su
- Department of Emergency, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Haixiang Ni
- Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, China
| | - Xiaohong Feng
- Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, China
| | - Jie Chen
- Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, China
| | - Xi Wang
- Central Laboratory, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
- Corresponding author. Central Laboratory, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310006, China.
| | - Qi Huang
- Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, China
- Corresponding author. Department of Endocrinology, First Affiliated Hospital of Zhejiang, Chinese Medicine University. Hangzhou, 310006, China.
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46
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Yeo E, Brubaker PL, Sloboda DM. The intestine and the microbiota in maternal glucose homeostasis during pregnancy. J Endocrinol 2022; 253:R1-R19. [PMID: 35099411 PMCID: PMC8942339 DOI: 10.1530/joe-21-0354] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 01/31/2022] [Indexed: 11/23/2022]
Abstract
It is now well established that, beyond its role in nutrient processing and absorption, the intestine and its accompanying gut microbiome constitute a major site of immunological and endocrine regulation that mediates whole-body metabolism. Despite the growing field of host-microbe research, few studies explore what mechanisms govern this relationship in the context of pregnancy. During pregnancy, significant maternal metabolic adaptations are made to accommodate the additional energy demands of the developing fetus and to prevent adverse pregnancy outcomes. Recent data suggest that the maternal gut microbiota may play a role in these adaptations, but changes to maternal gut physiology and the underlying intestinal mechanisms remain unclear. In this review, we discuss selective aspects of intestinal physiology including the role of the incretin hormone, glucagon-like peptide 1 (GLP-1), and the role of the maternal gut microbiome in the maternal metabolic adaptations to pregnancy. Specifically, we discuss how bacterial components and metabolites could mediate the effects of the microbiota on host physiology, including nutrient absorption and GLP-1 secretion and action, and whether these mechanisms may change maternal insulin sensitivity and secretion during pregnancy. Finally, we discuss how these pathways could be altered in disease states during pregnancy including maternal obesity and diabetes.
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Affiliation(s)
- Erica Yeo
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Patricia L Brubaker
- Department of Physiology, University of Toronto, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Deborah M Sloboda
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
- Department of Obstetrics, Gynecology and Pediatrics, McMaster University, Hamilton, ON, Canada
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47
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Gao H, Luo Z, Ji Y, Tang K, Jin Z, Ly C, Sears DD, Mahata S, Ying W. Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice. Nat Commun 2022; 13:565. [PMID: 35091566 PMCID: PMC8799656 DOI: 10.1038/s41467-022-28239-2] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 01/12/2022] [Indexed: 12/13/2022] Open
Abstract
Various microbial products leaked from gut lumen exacerbate tissue inflammation and metabolic disorders in obesity. Vsig4+ macrophages are key players preventing infiltration of bacteria and their products into host tissues. However, roles of islet Vsig4+ macrophages in the communication between microbiota and β cells in pathogenesis of obesity-associated islet abnormalities are unknown. Here, we find that bacterial DNAs are enriched in β cells of individuals with obesity. Intestinal microbial DNA-containing extracellular vesicles (mEVs) readily pass through obese gut barrier and deliver microbial DNAs into β cells, resulting in elevated inflammation and impaired insulin secretion by triggering cGAS/STING activation. Vsig4+ macrophages prevent mEV infiltration into β cells through a C3-dependent opsonization, whereas loss of Vsig4 leads to microbial DNA enrichment in β cells after mEV treatment. Removal of microbial DNAs blunts mEV effects. Loss of Vsig4+ macrophages leads to microbial DNA accumulation in β cells and subsequently obesity-associated islet abnormalities.
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Affiliation(s)
- Hong Gao
- Division of Endocrinology & Metabolism, University of California, San Diego, La Jolla, CA, 92093, USA
| | - Zhenlong Luo
- Division of Endocrinology & Metabolism, University of California, San Diego, La Jolla, CA, 92093, USA
- Department of Gastroenterology, Tongji Hospital, Tongji medical College, Huazhong University of Science and Technology, 430030, Wuhan, China
| | - Yudong Ji
- Division of Endocrinology & Metabolism, University of California, San Diego, La Jolla, CA, 92093, USA
- Department of Anesthesiology, Institute of Anesthesiology and Critical Care, Union Hospital, Tongji medical College, Huazhong University of Science and Technology, 430022, Wuhan, China
| | - Kechun Tang
- VA San Diego Healthcare System, La Jolla, CA, 92093, USA
| | - Zhongmou Jin
- Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, USA
| | - Crystal Ly
- Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, USA
| | - Dorothy D Sears
- College of Health Solutions, Arizona State University, Phoenix, AZ, 85004, USA
- Department of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA
- Department of Family Medicine, University of California, San Diego, La Jolla, CA, 92093, USA
- Moores Cancer Center, University of California, San Diego, La Jolla, 92093, CA, USA
| | - Sushil Mahata
- Division of Endocrinology & Metabolism, University of California, San Diego, La Jolla, CA, 92093, USA
- VA San Diego Healthcare System, La Jolla, CA, 92093, USA
| | - Wei Ying
- Division of Endocrinology & Metabolism, University of California, San Diego, La Jolla, CA, 92093, USA.
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48
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Li KP, Yuan M, Wu YL, Pineda M, Zhang CM, Chen YF, Chen ZQ, Rong XL, Turnbull JE, Guo J. A high-fat High-fructose Diet Dysregulates the Homeostatic Crosstalk Between Gut Microbiome, Metabolome and Immunity in an Experimental Model of Obesity. Mol Nutr Food Res 2022; 66:e2100950. [PMID: 35072983 DOI: 10.1002/mnfr.202100950] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/30/2021] [Indexed: 11/07/2022]
Abstract
SCOPE Ample evidence supports the prominent role of gut-liver axis in perpetuating pathological networks of high-fat high-fructose (HFF) diet induced metabolic disorders, however, the molecular mechanisms are still not fully understood. Herein, we aim to present a holistic delineation and scientific explanation for the crosstalk between the gut and liver, including the potential mediators involved in orchestrating the metabolic and immune systems. METHODS An experimental obesity associated metaflammation rat model was induced with a HFF diet. An integrative multi-omics analysis was then performed. Following the clues illustrated by the multi-omics discoveries, putative pathways were subsequently validated by RT-qPCR and Western blotting. RESULTS HFF diet led to obese phenotypes in rats, as well as histopathological changes. Integrated omics analysis showed there existed a strong interdependence among gut microbiota composition, intestinal metabolites and innate immunity regulation in the liver. Some carboxylic acids might contribute to gut-liver communication. Moreover, activation of the hepatic LPS-TLR4 pathway in obesity was confirmed. CONCLUSIONS HFF-intake disturbs gut flora homeostasis. Crosstalk between gut microbiota and innate immune system mediated hepatic metaflammation in obese rats, associated with LPS-TLR4 signaling pathway activation. Moreover, α-hydroxyisobutyric acid and some other organic acids may play a role as messengers in the liver-gut axis. High-fat high-fructose diet (HFF) induces obesity associated chronic inflammation; HFF dysregulates the rat intestinal metabolome and gut microbiota composition; HFF impacts hepatic expression of genes involved in innate immunity; Modulation of gut microbiota composition and innate immunity are connected partly via TLR4 signalling; Small molecular carboxylic acids are potential mediators of gut-liver axis communication in chronic obesity. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Kun-Ping Li
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Min Yuan
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Yong-Lin Wu
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Miguel Pineda
- Institute of infection, immunity & inflammation, University of Glasgow, University Place, Glasgow, G12 8TA, UK
| | - Chu-Mei Zhang
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Yan-Fen Chen
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Zhi-Quan Chen
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Xiang-Lu Rong
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
| | - Jeremy E Turnbull
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK
| | - Jiao Guo
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Key Laboratory of Glycolipid Metabolic Diseases, Ministry of Education, Guangzhou, 510006, China
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49
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Barbu E, Popescu MR, Popescu AC, Balanescu SM. Inflammation as A Precursor of Atherothrombosis, Diabetes and Early Vascular Aging. Int J Mol Sci 2022; 23:963. [PMID: 35055149 PMCID: PMC8778078 DOI: 10.3390/ijms23020963] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/12/2022] [Accepted: 01/13/2022] [Indexed: 02/07/2023] Open
Abstract
Vascular disease was for a long time considered a disease of the old age, but it is becoming increasingly clear that a cumulus of factors can cause early vascular aging (EVA). Inflammation plays a key role in vascular stiffening and also in other pathologies that induce vascular damage. There is a known and confirmed connection between inflammation and atherosclerosis. However, it has taken a long time to prove the beneficial effects of anti-inflammatory drugs on cardiovascular events. Diabetes can be both a product of inflammation and a cofactor implicated in the progression of vascular disease. When diabetes and inflammation are accompanied by obesity, this ominous trifecta leads to an increased incidence of atherothrombotic events. Research into earlier stages of vascular disease, and documentation of vulnerability to premature vascular disease, might be the key to success in preventing clinical events. Modulation of inflammation, combined with strict control of classical cardiovascular risk factors, seems to be the winning recipe. Identification of population subsets with a successful vascular aging (supernormal vascular aging-SUPERNOVA) pattern could also bring forth novel therapeutic interventions.
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Affiliation(s)
| | - Mihaela-Roxana Popescu
- Department of Cardiology, Elias Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, 011461 Bucharest, Romania; (E.B.); (S.-M.B.)
| | - Andreea-Catarina Popescu
- Department of Cardiology, Elias Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, 011461 Bucharest, Romania; (E.B.); (S.-M.B.)
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50
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Huan P, Wang L, He Z, He J. The Role of Gut Microbiota in the Progression of Parkinson's Disease and the Mechanism of Intervention by Traditional Chinese Medicine. Neuropsychiatr Dis Treat 2022; 18:1507-1520. [PMID: 35923300 PMCID: PMC9341349 DOI: 10.2147/ndt.s367016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 07/07/2022] [Indexed: 11/29/2022] Open
Abstract
Parkinson's disease (PD) is a common degenerative disease of the nervous system that seriously affects the quality of life of the patients. The pathogenesis of PD is not yet fully clear. Previous studies have confirmed that patients with PD exhibit obvious gut microbiota imbalance, while intervention of PD by regulating the gut microbiota has become an important approach to the prevention and treatment of this disease. Traditional Chinese medicine (TCM) has been shown to be safe and effective in treating PD. It has the advantages of affecting multiple targets. Studies have shown TCM can regulate gut microbiota. However, the specific mechanism of action is still unclear. Therefore, this article will mainly discuss the association of the alteration of the gut microbiota and the incidence of PD, the advantages of TCM in treating PD, and the mechanism of regulating gut microbiota by TCM to treat PD. It will clarify the target and mechanism of TCM treating PD by acting gut microbiota and provided a novel methodology for the prevention and treatment of PD.
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Affiliation(s)
- Pengfei Huan
- School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.,Shanghai Key Laboratory of Health Identification and Assessment, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China
| | - Li Wang
- School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.,Shanghai Key Laboratory of Health Identification and Assessment, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China
| | - Zhuqing He
- School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.,Shanghai Key Laboratory of Health Identification and Assessment, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China
| | - Jiancheng He
- School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.,Shanghai Key Laboratory of Health Identification and Assessment, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China
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