Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development
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 postulat...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-02-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.1965 |
| _version_ | 1797781052439134208 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Talima Pearson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T23:52:21Z |
| format | Article |
| id | doaj.art-8223f218e0d24b918621c7369cd70816 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-12T23:52:21Z |
| publishDate | 2019-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-8223f218e0d24b918621c7369cd708162023-07-13T12:30:56ZengWileyCancer Medicine2045-76342019-02-018261762810.1002/cam4.1965Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma developmentTalima Pearson0J. Gregory Caporaso1Monica Yellowhair2Nicholas A. Bokulich3Megha Padi4Denise J. Roe5Betsy C. Wertheim6Mark Linhart7Jessica A. Martinez8Cherae Bilagody9Heidie Hornstra10David S. Alberts11Peter Lance12Patricia A. Thompson13Pathogen and Microbiome Institute Northern Arizona University Flagstaff ArizonaPathogen and Microbiome Institute Northern Arizona University Flagstaff ArizonaUniversity of Arizona Cancer Center University of Arizona Tucson ArizonaPathogen and Microbiome Institute Northern Arizona University Flagstaff ArizonaDepartment of Molecular and Cellular Biology University of Arizona Tucson ArizonaUniversity of Arizona Cancer Center University of Arizona Tucson ArizonaUniversity of Arizona Cancer Center University of Arizona Tucson ArizonaPathogen and Microbiome Institute Northern Arizona University Flagstaff ArizonaUniversity of Arizona Cancer Center University of Arizona Tucson ArizonaPathogen and Microbiome Institute Northern Arizona University Flagstaff ArizonaPathogen and Microbiome Institute Northern Arizona University Flagstaff ArizonaUniversity of Arizona Cancer Center University of Arizona Tucson ArizonaUniversity of Arizona Cancer Center University of Arizona Tucson ArizonaUniversity of Arizona Cancer Center University of Arizona Tucson ArizonaAbstract 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.https://doi.org/10.1002/cam4.1965bile acidcolorectal adenomacolorectal cancergut microbiomeUrsodeoxycholic acid |
| spellingShingle | 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 Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development Cancer Medicine bile acid colorectal adenoma colorectal cancer gut microbiome Ursodeoxycholic acid |
| title | Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development |
| title_full | Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development |
| title_fullStr | Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development |
| title_full_unstemmed | Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development |
| title_short | Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development |
| title_sort | effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development |
| topic | bile acid colorectal adenoma colorectal cancer gut microbiome Ursodeoxycholic acid |
| url | https://doi.org/10.1002/cam4.1965 |
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