Bile acids and their receptors

Martinot, Emmanuelle; Sédes, Lauriane; Baptissart, Marine; Lobaccaro, Jean-Marc A.; Caira, Françoise; Beaudoin, Claude; Volle, David H.

doi:10.1016/j.mam.2017.01.006

Cited by 121 publications

(132 citation statements)

References 106 publications

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“…This includes cells of the immune system: bile acids reduce the expression of pro-inflammatory cytokines from monocytes, macrophages, DCs and the hepatic macrophages known as Kupffer cells (Brestoff and Artis, 2013; Martinot et al, 2017). These effects are primarily mediated by two different host receptors, the bile acid receptor (BAR; also known as nuclear receptor subfamily 1 group H member 4, NR1H4, or farnesoid X-activated receptor, FXR) and the G-protein-coupled bile acid receptor 1 (GPBAR1; also known as membrane-type receptor for bile acids, M-BAR, or TGR5).…”

Section: Microbiome-associated Metabolites That Shape the Immune Systemmentioning

confidence: 99%

“…A study evaluating genetic variations in NR1H4 found no association between single-nucleotide polymorphisms in this gene and IBD risk (Nijmeijer et al, 2011). The efficiency of bile-acid recycling depends on their biotransformation by the microbiome; however, the de novo synthesis of bile acids is subject to a strict feedback mechanism, which may limit the effect of increased excretion of bile acids in the absence of a fully functional microbiota (Martinot et al, 2017). Furthermore, while secondary bile acids are exclusively produced by gut bacteria, both primary and secondary bile acids are able to activate BAR and GPBAR1, and it is not clear what functional effects a shift in the balance of primary and secondary bile acids might have.…”

Section: Microbiome-associated Metabolites That Shape the Immune Systemmentioning

confidence: 99%

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Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

2017

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SUMMARY The human gastrointestinal tract is populated by a diverse, highly mutualistic microbial flora, which is known as the microbiome. Disruptions to the microbiome have been shown to be associated with severe pathologies of the host including metabolic disease, cancer and inflammatory bowel disease. Mood and behavior are also susceptible to alterations in the gut microbiota. A particularly striking example of the symbiotic effects of the microbiome is the immune system, whose cells depend critically on a diverse array of microbial metabolites for normal development and behavior. This includes metabolites that are produced by bacteria from dietary components; metabolites that are produced by the host and biochemically modified by gut bacteria; and metabolites that are synthesized de novo by gut microbes. In this review, we highlight the role of the intestinal microbiome in human metabolic and inflammatory diseases and focus in particular on the molecular mechanisms that govern the gut-immune axis.

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Section: Microbiome-associated Metabolites That Shape the Immune Systemmentioning

confidence: 99%

Section: Microbiome-associated Metabolites That Shape the Immune Systemmentioning

confidence: 99%

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

2017

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“…Moreover, gut microbiota deconjugate and metabolize primary bile acids into secondary bile acids in the gut . These bile acids modulate immunity by reducing the expression of proinflammatory cytokines in monocytes, macrophages, dendritic cells and hepatic macrophages (Kupffer cells) . Important effects of bacterial flora and their metabolites on the host's innate and adaptive immunity and inflammation are not limited to the intestinal tract, but extend to various other mechanisms and even to the brain …”

Section: The Integrity Of Intestinal Mucosal Barrier Depends On Gut Mmentioning

confidence: 99%

“…38 These bile acids modulate immunity by reducing the expression of proinflammatory cytokines in monocytes, macrophages, dendritic cells and hepatic macrophages (Kupffer cells). 39 Important effects of bacterial flora and their metabolites on the host's innate [40][41][42][43] and adaptive [44][45][46][47] immunity and inflammation are not limited to the intestinal tract, but extend to various other mechanisms and even to the brain. 48 Furthermore, the composition of gut microbiota can influence the host response to pathogens as well as its predisposition to disease.…”

Section: Intestinal Homeostasis Depends On Gut Microbiota and Theirmentioning

confidence: 99%

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

Guo

Liu

Hao

2020

J of Digest Diseases

190

110

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Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem—based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic‐associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.

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“…Bile acids (BAs) are synthesized from cholesterol in the liver and excreted into the intestine where they facilitate the absorption, transport and distribution of dietary lipids, lipid‐soluble vitamins, and steroids . Furthermore, BAs act as signaling molecules by activating nuclear receptors in hepatocytes; one of the important receptors is the farnesoid X receptor (FXR) . Changes in the BA pool size and composition may have metabolic regulatory consequences due to the FXR‐agonistic and antagonistic potencies of individual BA species.…”

Section: Introductionmentioning

confidence: 99%

Trimethylamine N‐Oxide Aggravates Liver Steatosis through Modulation of Bile Acid Metabolism and Inhibition of Farnesoid X Receptor Signaling in Nonalcoholic Fatty Liver Disease

Tan

Liu

Long

et al. 2019

Molecular Nutrition Food Res

158

107

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Scope Trimethylamine N‐oxide (TMAO), the metabolite of choline generated by gut microbiota, is associated with nonalcoholic fatty liver disease (NAFLD) and could influence bile acid (BA) metabolism. However, whether TMAO aggravates liver steatosis by modulating BA metabolism and the related mechanisms has not been investigated. Methods and results A case‐control study including biopsy‐proven NAFLD patients (n = 34) and controls (n = 14) is conducted to determine the correlation between TMAO and BA metabolism. Serum levels of total BA and the percentage of farnesoid X receptor (FXR)‐antagonistic BA species are markedly higher in NAFLD patients than in the controls. Serum levels of TMAO positively correlated with the serum levels of total BA and hepatic mRNA expression of cholesterol 7 alpha hydroxylase (CYP7A1). In a murine model, it is found that 18 weeks administration of TMAO impairs liver function and increases hepatic triglyceride accumulation and lipogenesis in mice fed with a high‐fat diet. TMAO increases BA synthesis and shifted hepatic BA composition toward FXR‐antagonistic activity. Knockdown of CYP7A1 via small interfering RNA or activation of FXR by GW4064 blocks the effect of TMAO‐induced lipogenesis in palmitic acid‐treated HepG2 cells. Conclusion TMAO aggravates liver steatosis by suppressing BA‐mediated hepatic FXR signaling.

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Bile acids and their receptors

Cited by 121 publications

References 106 publications

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

Trimethylamine N‐Oxide Aggravates Liver Steatosis through Modulation of Bile Acid Metabolism and Inhibition of Farnesoid X Receptor Signaling in Nonalcoholic Fatty Liver Disease

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