Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2013 May;58(5):949-55.
doi: 10.1016/j.jhep.2013.01.003. Epub 2013 Jan 16.

Modulation of the fecal bile acid profile by gut microbiota in cirrhosis

Genta Kakiyama  1 , William M Pandak, Patrick M Gillevet, Phillip B Hylemon, Douglas M Heuman, Kalyani Daita, Hajime Takei, Akina Muto, Hiroshi Nittono, Jason M Ridlon, Melanie B White, Nicole A Noble, Pamela Monteith, Michael Fuchs, Leroy R Thacker, Masoumeh Sikaroodi, Jasmohan S Bajaj
Affiliations
Comparative Study

Modulation of the fecal bile acid profile by gut microbiota in cirrhosis

Genta Kakiyama et al. J Hepatol. 2013 May.

Abstract

Background & 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 at studying 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 the 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 secondary/primary BA ratios.

Conclusions: Cirrhosis, especially advanced disease, is associated with a decreased conversion of primary to secondary fecal BAs, which is linked to abundance of key gut microbiome taxa.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: JSB is a consultant for Salix Pharmaceuticals

Figures

Fig 1
Fig 1. Change in fecal secondary/primary bile acid concentration ratios after rifaximin therapy in early cirrhotic patients
Figure 1a: LCA+DCA/CDCA+CA ratio, Figure 1b: LCA/CDCA ratio and Figure 1c: DCA/CA ratio change; there was a significant decrease in the fecal secondary to primary bile acid ratios after rifaximin therapy in early cirrhotic patients
See this image and copyright information in PMC

Comment in

References

    1. Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, et al. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2012;302:G168–175. - PMC - PubMed
    1. Bajaj JS, Hylemon PB, Ridlon JM, Heuman DM, Daita K, White MB, et al. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol. 2012;303:G675–685. - PMC - PubMed
    1. Chen Y, Yang F, Lu H, Wang B, Lei D, Wang Y, et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011;54:562–572. - PubMed
    1. Islam KB, Fukiya S, Hagio M, Fujii N, Ishizuka S, Ooka T, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011;141:1773–1781. - PubMed
    1. Ridlon JM, Kang DJ, Hylemon PB. Bile salt biotransformations by human intestinal bacteria. J Lipid Res. 2006;47:241–259. - PubMed

Publication types

MeSH terms