Investigation of the gut microbiome, bile acid composition and host immunoinflammatory response in a model of azoxymethane-induced colon cancer at discrete timepoints

dc.contributor.authorKeane, Jonathan M.
dc.contributor.authorWalsh, Calum J.
dc.contributor.authorCronin, P.
dc.contributor.authorBaker, Kevin J.
dc.contributor.authorMelgar, Silvia
dc.contributor.authorCotter, Paul D.
dc.contributor.authorJoyce, Susan A.
dc.contributor.authorGahan, Cormac G. M.
dc.contributor.authorHouston, Aileen M.
dc.contributor.authorHyland, Niall P.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2022-12-05T12:41:21Z
dc.date.available2022-12-05T12:41:21Z
dc.date.issued2022-11-23
dc.date.updated2022-11-24T11:20:47Z
dc.description.abstractBackground: Distinct sets of microbes contribute to colorectal cancer (CRC) initiation and progression. Some occur due to the evolving intestinal environment but may not contribute to disease. In contrast, others may play an important role at particular times during the tumorigenic process. Here, we describe changes in the microbiota and host over the course of azoxymethane (AOM)-induced tumorigenesis. Methods: Mice were administered AOM or PBS and were euthanised 8, 12, 24 and 48 weeks later. Samples were analysed using 16S rRNA gene sequencing, UPLC-MS and qRT-PCR. Results: The microbiota and bile acid profile showed distinct changes at each timepoint. The inflammatory response became apparent at weeks 12 and 24. Moreover, significant correlations between individual taxa, cytokines and bile acids were detected. One co-abundance group (CAG) differed significantly between PBS- and AOM-treated mice at week 24. Correlation analysis also revealed significant associations between CAGs, bile acids and the bile acid transporter, ASBT. Aberrant crypt foci and adenomas were first detectable at weeks 24 and 48, respectively. Conclusion: The observed changes precede host hyperplastic transformation and may represent early therapeutic targets for the prevention or management of CRC at specific timepoints in the tumorigenic process.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKeane, J.M., Walsh, C.J., Cronin, P., Baker, K., Melgar, S., Cotter, P.D., Joyce, S.A., Gahan, C.G.M., Houston, A., and Hyland, N.P. (2022) ‘Investigation of the gut microbiome, bile acid composition and host immunoinflammatory response in a model of azoxymethane-induced colon cancer at discrete timepoints’, British Journal of Cancer, https://doi.org/10.1038/s41416-022-02062-4.en
dc.identifier.doi10.1038/s41416-022-02062-4en
dc.identifier.endpage9en
dc.identifier.issn1532-1827
dc.identifier.journaltitleBritish Journal of Canceren
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/13895
dc.language.isoenen
dc.publisherSpringer Natureen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.relation.urihttps://doi.org/10.1038/s41416-022-02062-4
dc.rights© The Author(s),This version of the article has been accepted for publication, after peer review and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1038/s41416-022-02062-4.en
dc.subjectColon canceren
dc.subjectMicrobiomeen
dc.subjectColorectal cancer (CRC)en
dc.subjectMicrobiotaen
dc.subjectTumorigenesisen
dc.titleInvestigation of the gut microbiome, bile acid composition and host immunoinflammatory response in a model of azoxymethane-induced colon cancer at discrete timepointsen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 5 of 6
Loading...
Thumbnail Image
Name:
Keane_et_al_2022.pdf
Size:
1.65 MB
Format:
Adobe Portable Document Format
Description:
Accepted version
Loading...
Thumbnail Image
Name:
41416_2022_2062_MOESM1_ESM.pdf
Size:
424.32 KB
Format:
Adobe Portable Document Format
Description:
Additional file 1
Loading...
Thumbnail Image
Name:
41416_2022_2062_MOESM2_ESM.pdf
Size:
110.91 KB
Format:
Adobe Portable Document Format
Description:
Additional file 2
Loading...
Thumbnail Image
Name:
41416_2022_2062_MOESM3_ESM.pdf
Size:
112.73 KB
Format:
Adobe Portable Document Format
Description:
Additional file 3
Loading...
Thumbnail Image
Name:
41416_2022_2062_MOESM4_ESM.pdf
Size:
1.91 MB
Format:
Adobe Portable Document Format
Description:
Additional file 4
License bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description: