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

Abstract

Byron P Vaughn,1 Thomas Kaiser,2,3 Christopher Staley,2,3 Matthew J Hamilton,2 Jon Reich,1 Carolyn Graiziger,1 Stephanie Singroy,2 Amanda J Kabage,1 Michael J Sadowsky,2,4,5 Alexander Khoruts1,2 1Inflammatory Bowel Program, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA; 2BioTechnology Institute, University of Minnesota, St Paul, MN, USA; 3Department of Surgery, University of Minnesota, Minneapolis, MN, USA; 4Department of Soil, Water, and Climate, University of Minnesota, St Paul, MN, USA; 5Department of Plant and Microbial Biology, University of Minnesota, St Paul, MN, USA 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

Keywords

• Inflammatory bowel disease
• primary sclerosing cholangitis
• bile acids
• microbiota