Abstract LB-298: Gut microbiota changes in response to treatment with ursodeoxycholic acid

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA Compelling evidence suggests that the gut flora influences colorectal cancer risk through direct effects on colonic bile acid composition. Bile acids are widely implicated in the etiology of colorectal cancer and the strongest evidence is for the secondary bile acid deoxycholic acid. In a study of patients with prior colorectal adenomas who were randomized to ursodeoxycholic acid (n = 188 males, 64 females), a bile acid based intervention aimed at modulating bile acid composition, or placebo (n = 162 males, 89 females), we determined effects of the intervention on the gut microbiome through 16S rRNA sequencing and bile acid composition using mass spectrometry. We observe a consistent shift in microbial community phylogenetic composition for males (t = 5.83, p = 3.6e-8) and females (t = 3.14, p = 0.003) treated with UDCA. No effect was observed in the placebo group for either males (t = -0.08, p = 0.93) or females (t = -0.09, p = 0.92). This suggests that UDCA treatment, but not placebo treatment, is having an effect on the gut microbial communities of study participants. Interestingly, the microbiomes of the UDCA group do not change more than those of the placebo group: rather the magnitude of change is similar in the two groups, but UDCA treatment seems to drive specific microbiome changes. We also observe significant correlations between the gut microbiome composition and bile acid composition (r = 0.31, p<0.001). Specifically we find that (prior to treatment) bile acids including CA, CDCA, and UDCA are negatively correlated with diversity (richness) and to a lesser extent the abundance of Bacteroidetes (phylum) in the gut. These results are consistent with our previously reported observation that UDCA appears to have a greater effect in men for the prevention of colorectal adenomatous polyps, with risk-increasing effects for women. To our knowledge, this is the first study to correlate fecal bile acid levels with fecal microbial composition in humans or to assess the effect of the therapeutic bile acid UDCA on gut microbial composition. This study supports our observation that the efficacy of UDCA for the prevention of colorectal adenoma may be sex-dependent and suggests that the sex-specific effect may reflect differential effects of UDCA on the gut microbial community and the relationship between sex, the gut microbiome, and risk of colorectal adenomatous polyps. Citation Format: J Gregory Caporaso, Talima Pearson, Monia Yellowhair, Jessica Martinez, Peter Lance. Gut microbiota changes in response to treatment with ursodeoxycholic acid. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-298.