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,Patricia A. Thompson +14 more
TLDR
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.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 0.05). 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.read more
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Journal ArticleDOI
Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis.
TL;DR: In this paper , a review of recent studies on the involvement of gut microbiota-derived BAs in intestinal immunity, inflammation, and tumorigenesis along with human omics data to provide prospective insights into future prevention and treatment of IBD and CRC.
Journal ArticleDOI
The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing
Tianyu Liu,Xueli Song,Samiullah Khan,Yun Li,Zixuan Guo,Chuqiao Li,Sinan Wang,Wenxiao Dong,Wentian Liu,Bangmao Wang,Hailong Cao +10 more
TL;DR: Interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis is discussed and the critical role of bile acids receptors involving in CRC is summarized, and the rationale of multiple interventions for CRC management by regulatingbile acids–microbiota axis is addressed.
Journal ArticleDOI
Ursodeoxycholic acid and cancer: From chemoprevention to chemotherapy.
TL;DR: The present review is centred around the anticancer properties of UDCA and synthetic antitumor derivatives designed over the past 20 years, as well as the design of tumour-active derivatives, including UDCA-drug conjugates.
Book ChapterDOI
UDCA, NorUDCA, and TUDCA in Liver Diseases: A Review of Their Mechanisms of Action and Clinical Applications
TL;DR: Current experimental and clinical data regarding these BAs and its role in the treatment of certain liver diseases are summarized.
Journal ArticleDOI
Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside.
Min Yang,Yu Gu,Lingfeng Li,Tianyu Liu,Xueli Song,Yue Sun,Xiaocang Cao,Bangmao Wang,Kui Jiang,Hailong Cao +9 more
TL;DR: In this article, the bile acid-gut microbiota axis is closely connected with IBD pathogenesis and regulation of this axis may be a novel option for treating IBD, which is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear.
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