Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development

Talima Pearson, J. Gregory Caporaso, Monica Yellowhair, Nicholas A. Bokulich, Megha Padi, Denise J. Roe, Betsy C. Wertheim, Mark Linhart, Jessica A. Martinez, Cherae Bilagody, Heidie Hornstra, David S. Alberts, Peter Lance, Patricia A. Thompson

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

It has been previously reported that ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduced risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colorectal cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies. Using banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal adenomatous polyps, we compared change in the microbiome composition after a 3-year intervention in a subset of participants randomized to oral UDCA at 8-10 mg/kg of body weight per day (n = 198) or placebo (n = 203). Study participants randomized to UDCA experienced compositional changes in their microbiome that were statistically more similar to other individuals in the UDCA arm than to those in the placebo arm. This reflected a UDCA-associated shift in microbial community composition (P < 0.001), independent of sex, with no evidence of a UDCA effect on microbial richness (P > 0.05). These UDCA-associated shifts in microbial community distance metrics from baseline to end-of-study were not associated with risk of any or advanced adenoma (all P > 0.05) in men or women. Separate analyses of microbial networks revealed an overrepresentation of Faecalibacterium prausnitzii in the post-UDCA arm and an inverse relationship between F prausnitzii and Ruminococcus gnavus. In men who received UDCA, the overrepresentation of F prausnitzii and underrepresentation of R gnavus were more prominent in those with no adenoma recurrence at follow-up compared to men with recurrence. This relationship was not observed in women. Daily UDCA use modestly influences the relative abundance of microbial species in stool and affects the microbial network composition with suggestive evidence for sex-specific effects of UDCA on stool microbial community composition as a modifier of colorectal adenoma risk.

Original languageEnglish (US)
Pages (from-to)617-628
Number of pages12
JournalCancer Medicine
Volume8
Issue number2
DOIs
StatePublished - Feb 1 2019

Keywords

  • Ursodeoxycholic acid
  • bile acid
  • colorectal adenoma
  • colorectal cancer
  • gut microbiome

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Fingerprint Dive into the research topics of 'Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development'. Together they form a unique fingerprint.

  • Cite this

    Pearson, T., Caporaso, J. G., Yellowhair, M., Bokulich, N. A., Padi, M., Roe, D. J., Wertheim, B. C., Linhart, M., Martinez, J. A., Bilagody, C., Hornstra, H., Alberts, D. S., Lance, P., & Thompson, P. A. (2019). Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. Cancer Medicine, 8(2), 617-628. https://doi.org/10.1002/cam4.1965