Rattus norvegicus strain:F344/Ntac Targeted Locus (Loci)

Human epidemiological and animal model studies have shown that the presence of colon cancer is associated with certain microbiota. Previously, we re-derived genetically identical embryos of the Pirc (F344/NTac-Apc+/Pirc) rat model of familial adenomatous polyposis using surrogate dams, each harboring distinct gut microbiota (GM) that modulated adenoma susceptibility. Bacterial relative abundances as determined by 16S rDNA sequencing showed several taxa including the sulfate-reducing bacterium, Desulfovibrio spp. correlating with suppression of both tumor growth and phenotype penetrance as early as 1 month of age. We treated Pirc rats with a Type-1 secretion system (T1SS) competent, biofilm-forming and a mutant, biofilm-deficient strain of Desulfovibrio vulgaris Hildenborough (DvH). We found that the rats stably colonized with the biofilm-forming DvH strain, with the bacteria present at 4 months of age. Adenoma burden at sacrifice showed that the biofilm-competent strain significantly reduced colonic adenoma burden compared to the biofilm-deficient strain-treated rats. Simultaneously, we found a shift in the endogenous gut microbiota (GM) structure in the treated rats compared to the control animals. We also found an increase in fecal hydrogen sulfide levels in the control and biofilm-deficient rats, suggesting the role of H2S in disease susceptibility. Most importantly, we found that the biofilm-forming capacity of DvH enabled its engraftment within a complex GM population, significantly reducing tumor burden in Pirc rats.