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

Talima R Pearson, James G 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

3 Citations (Scopus)

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

Fingerprint

Ursodeoxycholic Acid
Adenoma
Microbiota
Bile Acids and Salts
Gastrointestinal Microbiome
Ruminococcus
Placebos
Adenomatous Polyps
Recurrence
Phase III Clinical Trials
Colorectal Neoplasms
Cohort Studies
Randomized Controlled Trials
Body Weight

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. / Pearson, Talima R; Caporaso, James G; Yellowhair, Monica; Bokulich, Nicholas A.; Padi, Megha; Roe, Denise J.; Wertheim, Betsy C.; Linhart, Mark; Martinez, Jessica A.; Bilagody, Cherae; Hornstra, Heidie; Alberts, David S.; Lance, Peter; Thompson, Patricia A.

In: Cancer Medicine, Vol. 8, No. 2, 01.02.2019, p. 617-628.

Research output: Contribution to journalArticle

Pearson, TR, Caporaso, JG, Yellowhair, M, Bokulich, NA, Padi, M, Roe, DJ, Wertheim, BC, Linhart, M, Martinez, JA, Bilagody, C, Hornstra, H, Alberts, DS, Lance, P & Thompson, PA 2019, 'Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development', Cancer Medicine, vol. 8, no. 2, pp. 617-628. https://doi.org/10.1002/cam4.1965
Pearson, Talima R ; Caporaso, James G ; Yellowhair, Monica ; Bokulich, Nicholas A. ; Padi, Megha ; Roe, Denise J. ; Wertheim, Betsy C. ; Linhart, Mark ; Martinez, Jessica A. ; Bilagody, Cherae ; Hornstra, Heidie ; Alberts, David S. ; Lance, Peter ; Thompson, Patricia A. / Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. In: Cancer Medicine. 2019 ; Vol. 8, No. 2. pp. 617-628.
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