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Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance

ABSTRACT: Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation, tumor growth, and therapy response. Gut microbes signal via metabolites, but how the metabolites impact CRC is largely unknown. We interrogated fecal metabolites associated with mouse models of colon tumorigenesis with varying mutational load. We found that microbial metabolites from healthy mice or humans were growth-repressive, and this response was attenuated in mice and patients with CRC. Microbial profiling revealed that Lactobacillus reuteri and its metabolite, reuterin were downregulated in mouse and human CRC. Reuterin altered redox balance, and reduced survival, and proliferation in colon cancer cells. Reuterin induced selective protein oxidation, and inhibited ribosomal biogenesis and protein translation. Exogenous Lactobacillus reuteri restricted mouse colon tumor growth, increased tumor reactive oxygen species, and decreased protein translation in vivo. Our findings indicate that a healthy microbiome and specifically, Lactobacillus reuteri, is protective against CRC through microbial metabolite exchange.

ORGANISM(S): synthetic construct Bacteria mouse gut metagenome feces metagenome

PROVIDER: GSE186880 | GEO | 2021/12/12

REPOSITORIES: GEO

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Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer I

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2019-11-12 | PXD011278 | Pride

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Inactivation of the Lactobacillus reuteri 100-23 ureC gene affects in vitro acid tolerance, and impairs ecological fitness in vivo

2012-09-30 | E-GEOD-36286 | biostudies-arrayexpress

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