A pilot study of fecal bile acid and microbiota profiles in inflammatory bowel disease and primary sclerosing cholangitis

Abstract

Introduction

Inflammatory bowel disease (IBD) is thought to arise from an abnormal immune response to the gut microbiota. IBD is associated with altered intestinal microbial community structure and functionality, which may contribute to inflammation and complications such as colon cancer and liver disease. Primary sclerosing cholangitis (PSC) is associated with IBD and markedly increases the risk of colon cancer. We hypothesized that secondary bile acids, which are products of microbial metabolism, are increased in PSC patients.

Aim

Here, we profiled the fecal bile acid composition and gut microbiota of participants with IBD and PSC, as well as healthy participants. Additionally, we tested the effects of vancomycin, a proposed treatment for PSC, on gut microbiota and fecal bile acid composition in participants with IBD and PSC.

Methods

Fecal samples were collected from patients with IBD, IBD/PSC and healthy controls and fecal bile acids and DNA for microbiota analysis were extracted. Fecal bile acids were averaged over a seven-day period. For subjects with IBD/PSC, oral vancomycin 500mg twice a day was administered and fecal samples were collected for up to eleven weeks.

Results

Participants with IBD and PSC had less fecal microbial diversity at baseline relative to controls. While there was some evidence of altered conversion of cholic acid to deoxycholic acid, no substantial differences were found in the fecal bile acid profiles of patients with IBD and PSC (n=7) compared to IBD alone (n=8) or healthy controls (n=8). Oral vancomycin was a potent inhibitor of secondary bile acid production in participants with IBD and PSC, particularly deoxycholic acid, although no changes in liver biochemistry patterns were noted over a two week period.

Conclusion

In this pilot study, bile acid profiles were overall similar among patients with IBD and PSC, IBD alone, and healthy controls. Microbiota diversity was reduced in those with PSC and IBD compared to IBD alone or healthy controls.

Keywords:

• vancomycin
• Crohn’s disease
• ulcerative colitis

Acknowledgments

Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure

BPV has received research support from Takeda, Celgene, Roche, Crestovo, and Diasorin and has received speaking/consulting income from Abbvie and Janssen. MJS has consulted for Crestovo. The authors report no other conflicts of interest in this work.

Author contributions

BPV contributed to the design, analysis, interpretation of data, and manuscript drafting. TK, CS, MJH, and SS contributed to the analysis, results, interpretation of data, and critical review of the manuscript. JR contributed to the design, collection of data, and critical review of the manuscript. CG and Amanda K contributed to design, collection of data, and critical review of the manuscript. MJS and Alexander K contributed to the design, interpretation of data, and critical review of the manuscript. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.