Targeted Screening from Highly Colitis-Resistant Pigs Can Alleviate Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is often accompanied by intestinal inflammation and disruption of intestinal epithelial structures, which are closely associated with changes in the intestinal microbiota. We previously revealed that Min pigs, a native Chinese breed, are more resistant to dextran sulfate sodium (DSS)-induced colitis than commercial Yorkshire pigs. Characterizing the microbiota in Min pigs would allow identification of the core microbes that confer colitis resistance. By analyzing the microbiota linked to the disease course in Min and Yorkshire pigs, we observed that spp. were enriched in Min pigs and positively correlated with pathogen resistance. Using targeted screening, we identified and validated MZ16 from Min pigs as a bacterial species with biofilm formation ability, superior salt and pH tolerance, and antimicrobial characteristics. Subsequently, we administered MZ16 to conventional or microbiota-deficient BALB/c mice with DSS-induced colitis to assess its efficacy in alleviating colitis. MZ16 partially counteracted DSS-induced colitis in conventional mice, but it did not mitigate DSS-induced colitis in microbiota-deficient mice. Further analysis revealed that MZ16 administration improved intestinal ecology and integrity and immunological barrier function in mice. Compared to the DSS-treated mice, mice preadministered MZ16 exhibited improved relative abundance of potentially beneficial microbes (, , , , , and ), reduced relative abundance of pathogenic microbes (), and maintained colonic OCLN and ZO-1 levels and IgA and SIgA levels. Furthermore, MZ16 reduced proinflammatory cytokine levels by reversing NF-κB and MAPK pathway activation in the DSS group. Overall, MZ16 from Min pigs had beneficial effects on a colitis mouse model by enhancing intestinal barrier functions and reducing inflammation in a gut microbiota-dependent manner.