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dc.contributor.author
Pearson, Talima
dc.contributor.author
Caporaso, J. Gregory
dc.contributor.author
Yellowhair, Monica
dc.contributor.author
Bokulich, Nicholas A.
dc.contributor.author
Padi, Megha
dc.contributor.author
Roe, Denise J.
dc.contributor.author
Wertheim, Betsy C.
dc.contributor.author
Linhart, Mark
dc.contributor.author
Martinez, Jessica A.
dc.contributor.author
Bilagody, Cherae
dc.contributor.author
Hornstra, Heidie
dc.contributor.author
Alberts, David S.
dc.contributor.author
Lance, Peter
dc.contributor.author
Thompson, Patricia A.
dc.date.accessioned
2020-08-17T07:49:35Z
dc.date.available
2020-08-12T10:10:36Z
dc.date.available
2020-08-17T07:49:35Z
dc.date.issued
2019-02
dc.identifier.issn
2045-7634
dc.identifier.other
10.1002/cam4.1965
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/431181
dc.identifier.doi
10.3929/ethz-b-000431181
dc.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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Bile Acid
en_US
dc.subject
Colorectal adenoma
en_US
dc.subject
Colorectal cancer
en_US
dc.subject
Gut microbiome
en_US
dc.subject
Ursodeoxycholic acid
en_US
dc.title
Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2019-01-16
ethz.journal.title
Cancer Medicine
ethz.journal.volume
8
en_US
ethz.journal.issue
2
en_US
ethz.pages.start
617
en_US
ethz.pages.end
628
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.publication.place
Oxford
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::09714 - Bokulich, Nicholas / Bokulich, Nicholas
en_US
ethz.date.deposited
2020-08-12T10:10:44Z
ethz.source
BATCH
ethz.eth
no
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-08-17T07:49:48Z
ethz.rosetta.lastUpdated
2020-08-17T07:49:48Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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