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

PeerJ

article

Eline Vanlancker¹  Barbara Vanhoecke¹  Andrea Stringer²  Tom Van de Wiele¹ 

[1] Center for Microbial Ecology and Technology ,(CMET), Ghent University;Sansom Institute for Health Research, University of South Australia

关键词: Irinotecan;    Chemotherapy;    Colon microbiota;    5-Fluorouracil;    Community analysis;    Gut;    Bacteria;    Short chain fatty acids;    16S rRNA sequencing;    Illumina amplicon sequencing;   

DOI  :  10.7717/peerj.4017

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Gastrointestinal 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.

【 授权许可】

CC BY