The Role of the Gut Microbiota in Bile Acid Metabolism

Ramírez-Pérez, Oscar; Cruz-Ramón, Vania; Chinchilla-López, Paulina; Méndez-Sánchez, Nahúm

doi:10.5604/01.3001.0010.5672

Cited by 272 publications

(229 citation statements)

References 45 publications

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“…The composition of the gut microbiome and its interaction with BAs affects FXR-mediated signaling in both the liver and intestine and is implicated in NAFLD pathogenesis. (20,22) Hence, we determined gut microbiome composition in a small exploratory subset of patients with available stool samples by 16S ribosomal RNA amplicon sequencing. The clinical characteristics of these patients is found in Supporting Table S2.…”

Section: Patients With Lean Nafld Have a Distinct Microbiota Profilementioning

confidence: 99%

Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation

et al. 2020

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Background and Aims Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult population. A significant subset of patients are lean, but their underlying pathophysiology is not well understood. Approach and Results We investigated the role of bile acids (BAs) and the gut microbiome in the pathogenesis of lean NAFLD. BA and fibroblast growth factor (FGF) 19 levels (a surrogate for intestinal farnesoid X receptor [FXR] activity), patatin‐like phospholipase domain containing 3 (PNPLA3), and transmembrane 6 superfamily member 2 (TM6SF2) variants, and gut microbiota profiles in lean and nonlean NAFLD were investigated in a cohort of Caucasian patients with biopsy‐proven NAFLD (n = 538), lean healthy controls (n = 30), and experimental murine models. Patients with lean NAFLD had a more favorable metabolic and histological profile compared with those with nonlean NAFLD (P < 0.05 for all). BA levels were significantly higher in NAFLD with advanced compared with earlier stages of liver fibrosis. Patients with lean NAFLD had higher serum secondary BA and FGF19 levels and reduced 7‐alpha‐hydroxy‐4‐cholesten‐3‐one (C4) levels (P < 0.05 for all). These differences were more profound in early compared with advanced stages of fibrosis (P < 0.05 for both). Lean patients demonstrated an altered gut microbiota profile. Similar findings were demonstrated in lean and nonlean murine models of NAFLD. Treating mice with an apical sodium‐dependent BA transporter inhibitor (SC‐435) resulted in marked increases in fgf15, a shift in the BA and microbiota profiles, and improved steatohepatitis in the lean model. Conclusions Differences in metabolic adaptation between patients with lean and nonlean NAFLD, at least in part, explain the pathophysiology and provide options for therapy.

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Section: Patients With Lean Nafld Have a Distinct Microbiota Profilementioning

confidence: 99%

Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation

et al. 2020

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“…Bile is essential for digestion and absorption of fats and removal of excess cholesterol, bilirubin, drugs, and toxic compounds (Kanehisa, Tanabe, Sato, & Morishima, 2017 Sánchez, 2017). Eubacterium lentum and Clostridium perfringens were reported to possess the capability to produce iso-bile acids Hirano, Masuda, Oda, & Mukai, 1981).…”

Section: Dominance Ofmentioning

confidence: 99%

Comparative study of gut microbiota in wild and captive Malaysian Mahseer (Tor tambroides)

et al. 2018

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Aims The aim of this study was to identify and compare the gut microbial community of wild and captive Tor tambroides through 16S rDNA metagenetic sequencing followed by functions prediction. Methods and results The library of 16S rDNA V3‐V4 hypervariable regions of gut microbiota was amplified and sequenced using Illumina MiSeq. The sequencing data were analyzed using Quantitative Insights into Microbial Ecology ( QIIME ) pipeline and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States ( PICRUS t). The most abundant bacterial phyla in both wild and captive T. tambroides were Firmicutes, Proteobacteria, Fusobacteria and Bacteroidetes. Cetobacterium spp., Peptostreptococcaceae family, Bacteroides spp., Phosphate solubilizing bacteria PSB ‐M‐3, and Vibrio spp. were five most abundant OTU in wild T. tambroides as compared to Cetobacterium spp., Citrobacter spp., Aeromonadaceae family, Peptostreptococcaceae family and Turicibacter spp. in captive T. tambroides . Conclusion In this study, the specimens of the wild T. tambroides contain more diverse gut microbiota than of the captive ones. The results suggested that Cetobacterium spp. is one of the core microbiota in guts of T. tambroides . Besides, high abundant Bacteroides spp., Citrobacter spp., Turicibacter spp., and Bacillus spp. may provide important functions in T. tambroides guts. Significance and impact of the study The results of this study provide significant information of T. tambroides gut microbiota for further understanding of their physiological functions including growth and disease resistance.

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“…Colonic absorption of BAs is facilitated by gut microbiota, which converts the conjugated BAs into more hydrophobic molecules to enable their reabsorption by passive diffusion across the cell membrane. [12][13][14] The entero-hepatic cycling of BAs is a highly efficient and tightly orchestrated process that not only provides an effective recycling mechanism to conserve and maintain a constant BA pool, but also serves as a mechanism to restrict BAs to the intestinal and hepatobiliary compartments. 15 Disruption of this process, primarily due to BA malabsorption or excessive biotransformation by gut microbiota, can increase the passage of BAs to the colon.…”

Section: Introductionmentioning

confidence: 99%

Western diet‐induced increase in colonic bile acids compromises epithelial barrier in nonalcoholic steatohepatitis

et al. 2020

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Abbreviations: CEB, colonic epithelial barrier; MetS, Metabolic Syndrome; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis. AbstractThere is compelling evidence implicating intestinal permeability in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain poorly understood. Here we examined the role of bile acids (BA) in western diet (WD)-induced loss of colonic epithelial barrier (CEB) function in mice with a genetic impairment in intestinal epithelial barrier function, junctional adhesion molecule A knockout mice, F11r −/− . WD-fed knockout mice developed severe NASH, which was associated with increased BA concentration in the cecum and loss of CEB function. Analysis of cecal BA composition revealed selective increases in primary unconjugated BAs in the WD-fed mice, which correlated with increased abundance of microbial taxa linked to BA metabolism. In vitro permeability assays revealed that chenodeoxycholic acid (CDCA), which was elevated in the cecum of WD-fed mice, increased paracellular permeability, while the BA-binding resin sevelamer hydrochloride protected against CDCA-induced loss of barrier function. Sequestration of intestinal BAs by in vivo delivery of sevelamer to WD-fed knockout mice attenuated colonic mucosal inflammation and improved CEB. Sevelamer also reduced hepatic inflammation and fibrosis, and improved metabolic derangements associated with NASH. Collectively, these findings highlight a hitherto unappreciated role for BAs in WD-induced impairment of the intestinal epithelial barrier in NASH. K E Y W O R D S bile acids, intestinal permeability, microbiome, NAFLD, NASH, tight junction 7090 | GUPTA eT Al. | MATERIALS AND METHODS | MiceJunctional adhesion molecule A (JAM-A) knock out mice (F11r −/− ) were generated as previously described. 9 Mice were bred and maintained at Emory University and the University of Pittsburgh Divisions of Animal Resources. All animal studies were approved by the Institutional Animal Care and Use Committees. | BA feeding experimentC57BL/6 mice were fed CDCA (3mg/gm body weight, Millipore Sigma, St. Louis, MO) mixed with FITC-conjugated dextran (4 kDa) (0.6 mg/gm body weight, Millipore Sigma, St. Louis, MO) solution by oral gavage following a 6 hours fast. After 3 hours, blood was collected and fluorescence intensity was measured using Fluorescence Spectrophotometer (Synergy 2, BioTek, Winooski, VT) as described previously. 9

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The Role of the Gut Microbiota in Bile Acid Metabolism

Cited by 272 publications

References 45 publications

Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation

Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation

Comparative study of gut microbiota in wild and captive Malaysian Mahseer (Tor tambroides)

Western diet‐induced increase in colonic bile acids compromises epithelial barrier in nonalcoholic steatohepatitis

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