P704 Bifidobacterium longum species protect murine colitis through different activation repertoires of immune cells

Abstract

Abstract Background Inflammatory bowel disease (IBD) is a chronic disease that causes an inappropriate immune response due to genetic and environmental factors. The scientific interest in mechanisms of probiotics are world-widely growing. Bifidobacterium plays an essential role in the maturation of the immune system, and the prevention of colitis and tumor. However, only limited reports on bifidobacterium isolated to prevent colitis and their exact mechanisms of action remain poorly understood. This study identifies the different anticolitic effects between B. breve strain and Bifidobacterium longum (B. longum) strain, the most abundant probiotic strains in lactating babies. We explore the different activation repertoire of the immune cell according to Bifidobacterium species and the mechanisms in these processes. Methods We administrated B. breve and B. longum ATCC by oral gavage 1×109 CFU to RAG1 KO mice. Colitis was induced with 2.5% DSS for 7 days. To assess the direct role of B. longum on ILCs, ILCs from B. breve- and B. longum-treated wild-type mice were transferred to RAG1 KO mice. We observed daily weight loss, stool consistency, and rectal bleeding of mice and transformed to the disease activity index (DAI) scores. Macrophages and T-cell subsets in splenocytes, lamina propria cells were analyzed by flow cytometry. Gene expression and cytokine profiles were determined using qRT-PCR. We performed whole-genome sequencing of reactive oxygen species (ROS)-resistant B. longum species using DNA full-sequencing analysis. Results The two functional strains of B. breve and B. longum ameliorate gut immunopathology during colitis in RAG1 knockout mice. However, B. longum but not B. breve, drastically restored body weight loss, DAI, and colon length compared to B. breve-treated group. We found that the anticolitic effect of B. longum is specialized by modulation of ILCs. Newly identified B. longum strain from the feces of healthy adults has ROS resistance even though it is anaerobic bacteria. The new B. longum strain exhibits ANI values of 94.92% with respect to B. longum ATCC 15697. The new B. longum strain has a strong colonization ability and improves DSS-induced colitis in the wild-type mice than other strains. Our data revealed genus-specific effects of bifidobacteria on colonization in the colon, and ILCs, thus discriminating a differential degree of modulation of immune cells. Conclusion We explore the different activation repertoire of the immune cell according to Bifidobacterium species and the mechanisms in these processes. These findings suggest that B. longum can be used as a potent immunomodulatory of ILCs, which has significant implications for IBD treatment.