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

Abstract 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