5-Fluorouracil and irinotecan (SN-38) have limited impact on colon microbial functionality and composition in vitro

dc.contributor.authorVanlancker, E.
dc.contributor.authorVanhoecke, B.
dc.contributor.authorStringer, A.
dc.contributor.authorVan de Wiele, T.
dc.date.issued2017
dc.description.abstractGastrointestinal mucositis is a debilitating side effect of chemotherapy treatment, with currently no treatment available. As changes in microbial composition have been reported upon chemotherapy treatment in vivo, it is thought that gut microbiota dysbiosis contribute to the mucositis etiology. Yet it is not known whether chemotherapeutics directly cause microbial dysbiosis, thereby increasing mucositis risk, or whether the chemotherapeutic subjected host environment disturbs the microbiome thereby aggravating the disease. To address this question, we used the M-SHIME®, an in vitro mucosal simulator of the human intestinal microbial ecosystem, as an experimental setup that excludes the host factor. The direct impact of two chemotherapeutics, 5-fluorouracil (5-FU) and SN-38 (active metabolite of irinotecan), on the luminal and mucosal gut microbiota from several human donors was investigated through monitoring fermentation activity and next generation sequencing. At a dose of 10 µM in the mucosal environment, 5-FU impacted the functionality and composition of the colon microbiota to a minor extent. Similarly, a daily dose of 10 µM SN-38 in the luminal environment did not cause significant changes in the functionality or microbiome composition. As our mucosal model does not include a host-compartment, our findings strongly indicate that a putative microbial contribution to mucositis is initially triggered by an altered host environment upon chemotherapy.
dc.description.statementofresponsibilityEline Vanlancker, Barbara Vanhoecke, Andrea Stringer and Tom Van de Wiele
dc.identifier.citationPeerJ, 2017; 2017(11):e4017-1-e4017-20
dc.identifier.doi10.7717/peerj.4017
dc.identifier.issn2167-8359
dc.identifier.issn2167-8359
dc.identifier.orcidStringer, A. [0000-0003-3245-5360]
dc.identifier.urihttp://hdl.handle.net/2440/120779
dc.language.isoen
dc.publisherPEER J
dc.rights© 2017 Vanlancker et al. Distributed under Creative Commons CC-BY 4.0.
dc.subject16S rRNA sequencing
dc.subject5-Fluorouracil
dc.subjectBacteria
dc.subjectChemotherapy
dc.subjectColon microbiota
dc.subjectCommunity analysis
dc.subjectGut
dc.subjectIllumina amplicon sequencing
dc.subjectIrinotecan
dc.subjectShort chain fatty acids
dc.title5-Fluorouracil and irinotecan (SN-38) have limited impact on colon microbial functionality and composition in vitro
dc.typeJournal article
pubs.publication-statusPublished

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