Biofilm competency of Desulfovibrio vulgaris Hildenborough facilitates colonization in the gut and represses adenoma development in a rat model of colon cancer
Human epidemiological and animal model studies have shown that the presence of colon cancer is associated with certain microbiota. Previous human colon cancer case-control reports and our preclinical model studies identify several bacterial taxa correlating with the suppression of tumor growth. This includes a sulfate-reducing bacteria from the genus Desulfovibrio, which correlates with fewer tumors and decreased phenotype penetrance as early as 1 month of age in rats. However, other studies have shown that Desulfovibrio spp. are decreased in relative abundance in healthy patient controls. To address this disparity we treated PIRC rats, a model of human familial colon cancer that harbored a complex gut microbiota, with biofilm-forming and biofilm-deficient strains of the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough (DvH). We found that the biofilm-forming DvH strain could stably colonize the rat colon, with the bacteria detected even at 3.5 months post treatment. The biofilm-deficient DvH mutant only transiently colonized the rat colon and was no longer detected in fecal samples one-week post treatment. The colonic adenoma burden at four months of age was significantly reduced in rats colonized with the biofilm- forming DvH compared to those treated with the biofilm-deficient DvH. We found a differential shift in the endogenous gut microbiota (GM) structure over time, with a notable increase in known mucin degraders in the buffer-treated control and biofilm-deficient DvH treated groups. These latter groups of rats also showed a higher level of expression of MUC2 in the colon, which encodes for the sulfonated mucin 2 expressed primarily in the gut and trachea. We also detected more dissolved sulfide in the feces from rats treated with either buffer or biofilm-deficient DvH compared to rats colonized with the biofilm-competent DvH. We found that the in vitro biofilm- forming capacity of DvH enabled in vivo engraftment of this bacterium within a complex GM population, altering the bacterial composition, and significantly reducing tumor burden in PIRC rats.