Chronic inflammation and gut microbiota dysbiosis, in particular the bloom of genotoxin-producing E. coli 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 E. coli strains in the azoxymethane/dextran sulfate sodium colitis model was driven by molybdoenzyme-dependent metabolic pathways. Oral administration of sodium tungstate inhibited E. coli molybdoenzymes and selectively decreased gut colonization with genotoxin-producing E. coli 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, Il10-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.

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Squamous cell carcinoma (SCC) is a common oral neoplasm in domestic cats, but there are only a few reports in wild felids. A captive 10-years-old, female Siberian tiger (Panthera tigris altaica), with history of chronic renal disease and serologically positive for Leishmania sp. developed a lytic mandibular nodule that was histologically diagnosed as SCC. At necropsy was also observed an exocrine pancreatic carcinoma, which was considered an incidental finding, and a chronic lympho-plasmocytic interstitial nephritis associated with a membranous glomerulopathy, compatible with the chronic renal disease presented by the animal. To the best of our knowledge this is the first report of an invasive and non-metastatic mandibular SCC in a Siberian tiger.