Diversification of host bile acids by members of the gut microbiota

Winston, Jenessa A.; Theriot, Casey M.

doi:10.1080/19490976.2019.1674124

Cited by 380 publications

(321 citation statements)

References 118 publications

(252 reference statements)

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“…Indeed, our results indicated that HDCA supplementation significantly increased fecal secondary BAs (HDCA and THDCA + TUDCA) and decreased fecal primary BA (TCA). Numerous evidences have demonstrated that secondary BAs are more toxic than their primary counterparts, and may damage the gut and lead to diseases 7,27 . In addition, TUDCA has been reported to exert neutral effect on proliferation of human preadipocytes and adipocytes 42 .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the relative abundance of FamilyXIIITCG‐001 , which belongs to order Clostridiales , was significantly increased ( P = .0054) after HDCA supplementation. The genus Clostridium is one of the intestinal bacteria which perform both BSH deconjugation and 7α‐dehydroxylation, 7,8 and plays an important role in the production of secondary BAs. Thus, FamilyXIIITCG‐001 might elicit the similar role to that of Clostridium and be involved in the generation of secondary BAs.…”

Section: Discussionmentioning

confidence: 99%

“…BAs elicit their regulatory roles mainly via BAs receptors, such as farnesoid X receptor (FXR), a member of the nuclear hormone receptor and Takeda G‐coupled protein receptor 5 (TGR5), a membrane G protein‐coupled receptor 2,5,6 . The primary BAs, including chenodeoxycholic acid (CDCA) and cholic acid (CA) in humans, CA, CDCA, α‐muricholic acid (α‐MCA), and β‐MCA in rodent, and CDCA and hyocholic acid (HCA) in pigs, are synthesized in the liver, and then, conjugated to taurine or glycine before they are excreted into the intestinal tract after ingestion of food 7 . Once in the ileum, primary BAs are modified by intestinal bacteria to form more toxic non‐conjugated secondary BAs, which include many chemically distinct secondary BAs such as deoxycholic acid (DCA), lithocholic acid (LCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and their conjugated forms and isomers 8 .…”

Section: Introductionmentioning

confidence: 99%

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Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR‐PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria

et al. 2020

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Bile acids (BAs) have been implicated in regulation of intestinal epithelial signaling and function. This study aimed to investigate the effects of hyodeoxycholic acid (HDCA) on intestinal epithelial cell proliferation and explore the underlying mechanisms. IPEC‐J2 cells and weaned piglets were treated with HDCA and the contributions of cellular signaling pathways, BAs metabolism profiles and gut bacteria were assessed. In vitro, HDCA suppressed IPEC‐J2 proliferation via the BAs receptor FXR but not TGR5. In addition, HDCA inhibited the PI3K/AKT pathway, while knockdown of FXR or constitutive activation of AKT eliminated the inhibitory effects of HDCA, suggesting that FXR‐dependent inhibition of PI3K/AKT pathway was involved in HDCA‐suppressed IPEC‐J2 proliferation. In vivo, dietary HDCA inhibited intestinal expression of proliferative markers and PI3K/AKT pathway in weaned piglets. Meanwhile, HDCA altered the BAs metabolism profiles, with decrease in primary BA and increase in total and secondary BAs in feces, and reduction of conjugated BAs in serum. Furthermore, HDCA increased abundance of the gut bacteria associated with BAs metabolism, and thereby induced BAs profiles alternation, which might indirectly contribute to HDCA‐suppressed cell proliferation. Together, HDCA suppressed intestinal epithelial cell proliferation through FXR‐PI3K/AKT signaling pathway, accompanied by alteration of BAs metabolism profiles induced by gut bacteria.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR‐PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria

et al. 2020

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“…Secondary bile acids, which form the vast majority of the bile acids in the colon, may also be passively reabsorbed and enter the entero-hepatic circulation. As a result of this extensive metabolism, the final bile salt pool is deeply influenced by the microbiota composition of the individual and more than 50 different secondary bile acids are found in feces [47,48]. Moreover, the bile acid pool is involved in the feedback mechanism of bile acid synthesis.…”

Section: Figurementioning

confidence: 99%

Gut–Liver Axis and Inflammasome Activation in Cholangiocyte Pathophysiology

Maroni

Ninfole

Pinto

et al. 2020

Cells

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The Nlrp3 inflammasome is a multiprotein complex activated by a number of bacterial products or danger signals and is involved in the regulation of inflammatory processes through caspase-1 activation. The Nlrp3 is expressed in immune cells but also in hepatocytes and cholangiocytes, where it appears to be involved in regulation of biliary damage, epithelial barrier integrity and development of fibrosis. Activation of the pathways of innate immunity is crucial in the pathophysiology of hepatobiliary diseases, given the strong link between the gut and the liver. The liver secretes bile acids, which influence the bacterial composition of the gut microbiota and, in turn, are heavily modified by microbial metabolism. Alterations of this balance, as for the development of dysbiosis, may deeply influence the composition of the bacterial products that reach the liver and are able to activate a number of intracellular pathways. This alteration may be particularly important in the pathogenesis of cholangiopathies and, in particular, of primary sclerosing cholangitis, given its strong association with inflammatory bowel disease. In the present review, we summarize current knowledge on the gut-liver axis in cholangiopathies and discuss the role of Nlrp3 inflammasome activation in cholestatic conditions.

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“…These substances may affect a myriad of signaling pathways that might directly influence metabolic dysfunction, and contribute to NAFLD development and progression. Importantly, gut microbiota can modulate BA metabolism contributing to diversification of host BA, thus regulating BA‐dependent pathways mediated by dedicated BA receptors, such as FXR and TGR5 . In addition, similar to ALD, early in the disease, individuals with NAFLD may show impaired BA secretion resulting in increased intracellular BA concentrations .…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota in non‐alcoholic fatty liver disease and alcohol‐related liver disease: Current concepts and perspectives

Arab

Arrese

Shah

2020

Hepatology Research

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The term, gut-liver axis, is used to highlight the close anatomical and functional relationship between the intestine and the liver. It has been increasingly recognized that the gut-liver axis plays an essential role in the development and progression of liver disease. In particular, in non-alcoholic fatty liver disease and alcohol-related liver disease, the two most common causes of chronic liver disease, a dysbiotic gut microbiota can influence intestinal permeability, allowing some pathogens or bacteriaderived factors from the gut reaching the liver through the enterohepatic circulation contributing to liver injury, steatohepatitis, and fibrosis progression. Pathways involved are multiple, including changes in bile acid metabolism, intestinal ethanol production, generation of short-chain fatty acids, and other by-products. Bile acids act through dedicated bile acid receptors, farnesoid X receptor and TGR5, in both the ileum and the liver, influencing lipid metabolism, inflammation, and fibrogenesis. Currently, both non-alcoholic fatty liver disease and alcohol-related liver disease lack effective therapies, and therapeutic targeting of gut microbiota and bile acids enterohepatic circulation holds promise. In this review, we summarize current knowledge about the role of gut microbiota in the pathogenesis of non-alcoholic fatty liver disease and alcohol-related liver disease, as well as the relevance of microbiota or bile acid-based approaches in the management of those liver diseases.

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Diversification of host bile acids by members of the gut microbiota

Cited by 380 publications

References 118 publications

Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR‐PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria

Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR‐PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria

Gut–Liver Axis and Inflammasome Activation in Cholangiocyte Pathophysiology

Gut microbiota in non‐alcoholic fatty liver disease and alcohol‐related liver disease: Current concepts and perspectives

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