P0158Clostridium butyricum regulates T-helper 17 cells-related immune response in dextran sodium sulfate-induced colitis mice by targeting Toll-like receptor 2

Background To explore the mechanism by which Clostridium butyricum (C. butyricum) regulates the immune response in dextran sodium sulfate (DSS)-induced colitis in mice. Methods Mouse colitis was induced by 5% DSS for 7 days. We treated BALB/c mice with C. butyricum by gavage and anti-CD282 via intraperitoneal injection to block Toll-like receptor (TLR) 2. The disease activity index (DAI) and histological damage scores were calculated, the expression of TLR2, MyD88, NF-κBp65, IL17, IL23, and RORγt were detected by immunohistochemistry, western blot, and quantitative real-time PCR (qRT-PCR). Flow cytometry was used to detect T-helper (Th) 17 cells in peripheral blood of mice. Results Treatment with C. butyricum decreased the DAI and histological damage scores, depending on the down-regulating the expression of TLR2, MyD88, and NF-κBp65 of mouse colon tissue (P < 0.05). However, these effects were weakened after blocking TLR2. In addition, C. butyricum decreased the proportion of Th17 cells in the peripheral blood and down-regulated the expression of IL17, IL23, and RORγt of mouse colon tissue (P < 0.05). These effects were also weakened when TLR2 was blocked. Conclusion C. butyricum plays a protective role in the DSS-induced mouse colitis by inhibiting the expression of IL17, IL23, and RORγt and down-regulate Th17 cells. C. butyricum partly achieves this by partially inhibiting the TLR2/MyD88/NF-κB signaling pathway. References: 1. Bsat M, Chapuy L, Rubio M, et al. Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn’s Disease and Ulcerative Colitis Patients. Front Immunol. 2019;10:1177. 2. Barros PO, Dias ASO, Kasahara TM, et al. Expansion of IL-6+ Th17-like cells expressing TLRs correlates with microbial translocation and neurological disabilities in NMOSD patients. J Neuroimmunol. 2017;307:82-90. 3. Pan LL, Niu W, Fang X, et al. Clostridium butyricum Strains Suppress Experimental Acute Pancreatitis by Maintaining Intestinal Homeostasis. Mol Nutr Food Res. 2019:e1801419. 4. Jia L, Li D, Feng N, et al. Anti-diabetic Effects of Clostridium butyricum CGMCC0313.1 through Promoting the Growth of Gut Butyrate-producing Bacteria in Type 2 Diabetic Mice. Sci Rep. 2017;7(1):7046. Conflict of interest: Dr. Xie, Ying: No conflict of interest