Biofilm competency of Desulfovibrio vulgaris Hildenborough facilitates colonization in the gut and represses adenoma development in a rat model of colon cancer
biorxiv(2022)
摘要
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.
### Competing Interest Statement
The authors have declared no competing interest.
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关键词
colonization cancer,adenoma development,hildenborough
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