Role and Mechanism of Gut Microbiota in Human Disease

Frontiers in Cellular and Infection Microbiology, Journal Year: 2021, Volume and Issue: 11

Published: March 17, 2021

The human gut microbiome is a huge microbial community that plays an irreplaceable role in life. With the further development of research, influence intestinal flora on diseases has been gradually excavated. Gut microbiota (GM) dysbiosis adverse health effects body will lead to variety chronic diseases. underlying mechanisms GM are incredibly complicated. This review focuses regulation and mechanism neurodegenerative diseases, cardiovascular metabolic gastrointestinal thus providing potential target for prevention treatment disease.

Language: Английский

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Gut-liver axis: Pathophysiological concepts and clinical implications

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1700 - 1718

Published: Oct. 7, 2022

Language: Английский

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Bile acid metabolism and signaling, the microbiota, and metabolic disease

Pharmacology & Therapeutics, Journal Year: 2022, Volume and Issue: 237, P. 108238 - 108238

Published: July 2, 2022

Language: Английский

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Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(10), P. 1752 - 1766.e8

Published: Aug. 16, 2023

Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged distinct mechanistic pathways implicated in development NAFLD. Here, we report group gut microbiota-modified bile acids (BAs), hyodeoxycholic acid (HDCA) species, are negatively correlated with presence and severity HDCA treatment has been shown to alleviate NAFLD multiple mouse models by inhibiting intestinal farnesoid X receptor (FXR) upregulating hepatic CYP7B1. Additionally, significantly increased abundances probiotic species such Parabacteroides distasonis, which enhances lipid catabolism through acid-hepatic peroxisome proliferator-activated alpha (PPARα) signaling, turn upregulates FXR. These findings suggest therapeutic potential for treating NAFLD, unique mechanism simultaneously activating CYP7B1 PPARα.

Language: Английский

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Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(5), P. 2129 - 2149

Published: Dec. 22, 2021

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, actually, new concept metaflammation has been proposed to define the state metabolism connected immunological adaptations. Amongst continuously increased list systemic metabolites in regulation immune system, bile acids (BAs) represent distinct class implicated whole process CMD development because its multifaceted roles shaping immunometabolism. BAs can directly modulate system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, are key determinants maintaining dynamic communication between host microbiota. Importantly, targeting Farnesoid X receptor (FXR) other nuclear receptors play regulating homeostasis lipids, glucose, amino acids. axis per se susceptible intervention, thereby may constitute reciprocal regulatory loop metaflammation. We thus propose that represents core coordinator integrating immunometabolism CMD. provide an updated summary intensive discussion about how shape both innate adaptive function as inflammation conditions

Language: Английский

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Hyocholic acid species as novel biomarkers for metabolic disorders

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: March 5, 2021

Hyocholic acid (HCA) is a major bile (BA) species in the BA pool of pigs, known for its exceptional resistance to spontaneous development diabetic phenotypes. HCA and derivatives are also present human blood urine. We investigate whether profiles can predict metabolic disorders. find first cohort (n = 1107) that both obesity diabetes associated with lower serum concentrations species. A separate study 91) validates this finding further reveals individuals pre-diabetes levels feces. Serum increase patients after gastric bypass surgery 38) remission two years surgery. The results replicated independent, prospective cohorts 132 n 207), where found be strong predictors disorders 5 10 years, respectively. These findings underscore association diabetes, demonstrate feasibility using assess future risk developing abnormalities.

Language: Английский

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Gut Microbiota and Type 2 Diabetes Mellitus: Association, Mechanism, and Translational Applications

Mediators of Inflammation, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 12

Published: Aug. 17, 2021

Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology, including type 2 diabetes mellitus (T2DM). Metabolites and bacterial components of gut affect the initiation progression T2DM by regulating inflammation, immunity, metabolism. Short-chain fatty acids, secondary bile acid, imidazole propionate, branched-chain amino lipopolysaccharide are main molecules related T2DM. Many studies have investigated T2DM, particularly those butyrate-producing bacteria. Increasing evidence demonstrated that fecal transplantation probiotic capsules useful strategies preventing diabetes. In this review, we aim elucidate complex association between metabolism, immune disorders, underlying mechanisms, translational applications microbiota. This review will provide novel insight into developing individualized therapy for patients based on immunometabolism.

Language: Английский

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Melatonin mitigates aflatoxin B1‐induced liver injury via modulation of gut microbiota/intestinal FXR/liver TLR4 signaling axis in mice

Journal of Pineal Research, Journal Year: 2022, Volume and Issue: 73(2)

Published: June 2, 2022

Abstract Aflatoxin B1 (AFB1) is a widespread contaminant in foods and feedstuffs, its target organ the liver. Melatonin (MT) has been shown to alleviate inflammation organs remodel gut microbiota animals humans. However, underlying mechanism by which MT alleviates AFB1‐induced liver injury remains unclear. In present study, pretreatment markedly increased expression of intestinal tight junction proteins (ZO‐1, Occludin, Claudin‐1), decreased permeability, reduced production gut‐derived Lipopolysaccharide (LPS) remodeled microbiota, ultimately alleviated mice. Interestingly, failed exert beneficial effects on intestine antibiotic‐treated Meanwhile, significantly farnesoid X receptor (FXR) protein ileum, TLR4/NF‐κB signaling pathway‐related messenger RNA (mRNA) (TLR4, MyD88, p‐p65, p‐IκBα) livers AFB1‐exposed Subsequently, Gly‐β‐MCA, an intestine‐selective FXR inhibitor, blocked alleviating effect through increasing liver‐specific mRNA p‐IκBα). conclusion, ameliorated potential may be related regulate microbiota/intestinal FXR/liver TLR4 axis, provides strong evidence for protection inflammation.

Language: Английский

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Gut microbiome and bile acids in obesity-related diseases

Best Practice & Research Clinical Endocrinology & Metabolism, Journal Year: 2021, Volume and Issue: 35(3), P. 101493 - 101493

Published: Feb. 10, 2021

Dysbiosis has been implemented in the etiologies of obesity-related chronic diseases such as type 2 diabetes, NAFLD and cardiovascular diseases. Bile acids, a class amphipathic steroids produced liver extensively modified by microbiome, are increasingly recognized actors onset progression these Indeed, human obesity is associated with altered bile acid metabolism. acids facilitate intestinal fat absorption but also exert hormone-like functions through activation nuclear membrane-bound receptors thereby modulate glucose, lipid energy metabolism, integrity immunity. acid-signaling pathways have thus identified potential pharmacological targets for Interfering microbiome composition may be considered, liver- microbiome-derived species different signaling functions. This review summarizes recent developments this rapidly expanding field research addresses clinical prospects interference

Language: Английский

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Gut commensalParabacteroides distasonisalleviates inflammatory arthritis

Gut, Journal Year: 2023, Volume and Issue: 72(9), P. 1664 - 1677

Published: Jan. 5, 2023

Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed identify potential probiotic gut microbes that can ameliorate development RA.Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing shotgun metagenomics. Collagen-induced arthritic mice TNF-α transgenic were used evaluate roles commensal Parabacteroides distasonis RA. The effects P. distasonis-derived microbial metabolites on differentiation CD4+ T cells macrophage polarisation also investigated.The relative abundance new-onset history disease downregulated this decrease negatively correlated Disease Activity Score-28 (DAS28). Oral treatment live (LPD) considerably ameliorated pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic (DCA), isolithocholic (isoLCA) 3-oxolithocholic (3-oxoLCA) had similar synergistic In addition directly inhibiting Th17 cells, 3-oxoLCA isoLCA identified as TGR5 agonists promoted M2 macrophages. A specific synthetic inhibitor bile salt hydrolase attenuated antiarthritic LPD by reducing production these four acids. natural product ginsenoside Rg2 exhibited its anti-RA promoting growth distasonis.P. might represent prebiotic agents

Language: Английский

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