Modulation of the Fecal Bile Acid Profile by Gut Microbiota in Cirrhosis

By Genta Kakiyama, W. Pandak, Patrick Gillevet, P. Hylemon, D. Heuman, Kalyani Daita, H. Takei, Akina Muto, Hiroshi Nittono, Jason M. Ridlon and 7 more. Journal of Hepatology, 2013

739 citations recorded by the source corpus.

Background and Aims The 7α-dehydroxylation of primary bile acids (BAs), chenodeoxycholic (CDCA) and cholic acid (CA) into the secondary BAs, lithocholic (LCA) and deoxycholic acid (DCA) is a key function of the gut microbiota. We aimed to study the linkage between fecal BAs and gut microbiota in cirrhosis since this could help understand cirrhosis progression. Methods Fecal microbiota were analyzed by culture-independent multitagged-pyrosequencing, fecal BAs using HPLC and serum BAs using LC-MS in controls, early (Child A), and advanced cirrhotics(Child B/C). A subgroup of early cirrhotics underwent BA and microbiota analysis before/after eight weeks of rifaximin. Results Cross-sectional: 47 cirrhotics(24 advanced) and 14 controls were included. In feces, advanced cirrhotics had the lowest total, secondary, secondary/primary BA ratios, and highest primary BAs compared to early cirrhotics and controls. Secondary fecal BAs were detectable in all controls but in a significantly lower proportion of cirrhotics (p<0.002). Serum primary BAs were higher in advanced cirrhotics compared to the rest. Cirrhotics, compared to controls, had a higher Enterobacteriaceae (potentially pathogenic) but lower Lachonospiraceae, Ruminococcaceae and Blautia (7α-dehydroxylating bacteria) abundance. CDCA was positively correlated with Enterobacteriaceae(r=0.57, p<0.008) while Ruminococcaceae were positively correlated with DCA(r=0.4, p<0.05). A positive correlation between Ruminococcaceae and DCA/CA (r=0.82, p<0.012) and Blautia with LCA/CDCA (r=0.61, p<0.03) was also seen. Prospective study: Post-rifaximin, six early cirrhotics had reduction in Veillonellaceae and in the secondary/primary BA ratios. Conclusions Cirrhosis, especially advanced disease, is associated with a decreased conversion of primary to secondary fecal BAs which is linked with abundance of key gut microbiome taxa.

Subfields: Hepatology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/bb845e3022545f10577683947190540e6ac0354f

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In Hepatology

1. J. Y. Chiang
2. Natascha Roehlen
3. E. Crouchet
4. T. Baumert

In Molecular Biology

1. Tiangang Li
2. J. Y. Chiang

In Oncology

1. Tiangang Li
2. J. Y. Chiang
3. David S. Wishart

Citations in the corpus

• Bile Acid Signaling in Metabolic Disease and Drug Therapy (2014, background): “Bacterial dysbiosis has been associated with IBDs, obesity, type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), liver cirrhosis, and cancer (Kakiyama et al., 2013; Ridlon et al., 2013, 2014; Duseja and Chawla, 2014; Joyce and Gahan, 2014).”
• Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives (2020, background): “Moreover, highlighting the reciprocal interaction of bile acids and the gut microbiome, reduced excretion of primary bile acids in liver fibrosis with compromised liver function directly affects composition of the gut microbiome [119,121].”
• The Cirrhosis Dysbiosis Ratio defines Changes in the Gut Microbiome Associated with Cirrhosis and its Complications (2013, neutral): “We found in our prior studies that cirrhosis and HE were accompanied by reduced relative abundance of taxa considered benign and autochthonous, including Lachnospiraceae, Ruminococcaceae, and Clostridialies Incertae Sedis XIV (from now on called Clostridialies XIV) and a relatively higher abundance ”
• Blautia—a new functional genus with potential probiotic properties? (2021, background): “A few studies have also reported the relationship of decreased abundance of Blautia with ileal pouch–anal anastomosis and liver cirrhosis.(112,113) Blautia, as a genus of commensal obligate anaerobic bacteria, plays an important role in maintaining environmental balance in the intestine and preventi”
• Gut microbiome based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease (2017, neutral): “(Kakiyama et al., 2013) In addition, some members of the gut microbiota can convert choline to trimethylamine, which can induce liver injury leading to steatohepatitis.”