Editing of the gut microbiota reduces carcinogenesis in mouse models of colitis-associated colorectal cancer.

Zhu W, Miyata N, Winter MG, Arenales A, Hughes ER, Spiga L, Kim J, Sifuentes-Dominguez L, Starokadomskyy P, Gopal P, Byndloss MX, Santos RL, Burstein E, Winter SE
J Exp Med. 2019 216 (10): 2378-2393

PMID: 31358565 · PMCID: PMC6781011 · DOI:10.1084/jem.20181939

Chronic inflammation and gut microbiota dysbiosis, in particular the bloom of genotoxin-producing strains, are risk factors for the development of colorectal cancer. Here, we sought to determine whether precision editing of gut microbiota metabolism and composition could decrease the risk for tumor development in mouse models of colitis-associated colorectal cancer (CAC). Expansion of experimentally introduced strains in the azoxymethane/dextran sulfate sodium colitis model was driven by molybdoenzyme-dependent metabolic pathways. Oral administration of sodium tungstate inhibited molybdoenzymes and selectively decreased gut colonization with genotoxin-producing and other Enterobacteriaceae. Restricting the bloom of Enterobacteriaceae decreased intestinal inflammation and reduced the incidence of colonic tumors in two models of CAC, the azoxymethane/dextran sulfate sodium colitis model and azoxymethane-treated, -deficient mice. We conclude that metabolic targeting of protumoral Enterobacteriaceae during chronic inflammation is a suitable strategy to prevent the development of malignancies arising from gut microbiota dysbiosis.

© 2019 Zhu et al.

MeSH Terms (10)

Animals Colitis Colorectal Neoplasms Dextran Sulfate Dysbiosis Escherichia coli Gastrointestinal Microbiome Interleukin-10 Mice Neoplasms, Experimental

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