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

Keane, Jonathan M.; Walsh, Calum J.; Cronin, P.; Baker, Kevin J.; Melgar, Silvia; Cotter, Paul D.; Joyce, Susan A.; Gahan, Cormac G. M.; Houston, Aileen M.; Hyland, Niall P.

Access to this article is restricted until 6 months after publication by request of the publisher.. Restriction lift date: 2023-05-23

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

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dc.check.date	2023-05-23
dc.check.info	Access to this article is restricted until 6 months after publication by request of the publisher.	en
dc.contributor.author	Keane, Jonathan M.
dc.contributor.author	Walsh, Calum J.
dc.contributor.author	Cronin, P.
dc.contributor.author	Baker, Kevin J.
dc.contributor.author	Melgar, Silvia
dc.contributor.author	Cotter, Paul D.
dc.contributor.author	Joyce, Susan A.
dc.contributor.author	Gahan, Cormac G. M.
dc.contributor.author	Houston, Aileen M.
dc.contributor.author	Hyland, Niall P.
dc.contributor.funder	Science Foundation Ireland	en
dc.date.accessioned	2022-12-05T12:41:21Z
dc.date.available	2022-12-05T12:41:21Z
dc.date.issued	2022-11-23
dc.date.updated	2022-11-24T11:20:47Z
dc.description.abstract	Background: 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.status	Peer reviewed	en
dc.description.version	Accepted Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Keane, 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.doi	10.1038/s41416-022-02062-4	en
dc.identifier.endpage	9	en
dc.identifier.issn	1532-1827
dc.identifier.journaltitle	British Journal of Cancer	en
dc.identifier.startpage	1	en
dc.identifier.uri	https://hdl.handle.net/10468/13895
dc.language.iso	en	en
dc.publisher	Springer Nature	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/	en
dc.relation.uri	https://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.subject	Colon cancer	en
dc.subject	Microbiome	en
dc.subject	Colorectal cancer (CRC)	en
dc.subject	Microbiota	en
dc.subject	Tumorigenesis	en
dc.title	Investigation of the gut microbiome, bile acid composition and host immunoinflammatory response in a model of azoxymethane-induced colon cancer at discrete timepoints	en
dc.type	Article (peer-reviewed)	en