PMID- 31576093 OWN - NLM STAT- MEDLINE DCOM- 20200226 LR - 20200226 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 25 IP - 36 DP - 2019 Sep 28 TI - Clostridium butyricum alleviates intestinal low-grade inflammation in TNBS-induced irritable bowel syndrome in mice by regulating functional status of lamina propria dendritic cells. PG - 5469-5482 LID - 10.3748/wjg.v25.i36.5469 [doi] AB - BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gas-troenterological diseases characterized by abnormal visceral sensitivity and low-grade inflammation. The role of Clostridium butyricum (C. butyricum) in reducing intestinal low-grade inflammation via immune pathways has been well defined. However, the detailed mechanisms of the effects of C. butyricum on intestinal mucosal immunity, especially on immune cells of the lamina propria, remain unclear. Dendritic cells (DCs), which are important immune cells, secrete proinflammatory cytokines (IL-1beta, IL-6, and others) and express T cell immuno-globulin and mucin domain-3 (TIM3), promoting proliferation and activation of DCs, and mediating Th1 and Th17 inflammatory responses. AIM: To investigate the role of DCs in the development of IBS in a rat model and to understand the regulation of DCs after C. butyricum intervention. METHODS: An IBS animal model was established using C57BL/6 mice, and C. butyricum was continuously administered via the intragastric route to simulate different intestinal immune states. Intestinal visceral hypersensitivity and histopathology were assessed using the abdominal withdrawal reflex (AWR) test and hematoxylin & eosin (H&E) staining, respectively. The expression of proinflammatory cytokines (IL-1beta and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. Flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the lamina propria dendritic cells (LPDCs). The regulatory effect of C. butyricum was verified in bone marrow-derived dendritic cells by in vitro experiments. RESULTS: The secretion of proinflammatory cytokines (IL-1beta and IL-6) in mice with IBS was significantly increased compared with that of the control group, which suggested that the intestinal mucosa in mice with IBS was in a low-grade inflammatory state. The expression of CD11C+CD80+ and CD11c+TIM3+ in intestinal LPDCs in mice with IBS increased significantly. Meanwhile, the cytokines (IL-1beta and IL-6) were significantly reduced after the intervention with probiotic C. butyricum. The amount and function of LPDCs and the TIM3 on the surface of the LPDCs were decreased with the alleviation of the intestinal inflammatory response. CONCLUSION: The results suggest that C. butyricum regulates the amount and functional status of LPDCs in the intestinal mucosa of mice with IBS, and therefore modulates the local immune response in the intestine. CI - (c)The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved. FAU - Zhao, Qin AU - Zhao Q AD - Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China. FAU - Yang, Wen-Rong AU - Yang WR AD - Department of Clinical Nutrition, Taian City Central Hospital, Taian 271000, Shandong Province, China. FAU - Wang, Xiao-Hong AU - Wang XH AD - Department of Gastroenterology, Taian City Central Hospital, Taian 271000, Shandong Province, China. FAU - Li, Gai-Qin AU - Li GQ AD - Department of Gastroenterology, Taian City Central Hospital, Taian 271000, Shandong Province, China. FAU - Xu, Lei-Qi AU - Xu LQ AD - Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China. FAU - Cui, Xiao AU - Cui X AD - Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China. FAU - Liu, Yang AU - Liu Y AD - Department of Medicine, Beijing 316 Hospital, Beijing 100093, China. FAU - Zuo, Xiu-Li AU - Zuo XL AD - Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China. zuoxiuli_s@163.com. LA - eng PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) SB - IM MH - Animals MH - Clostridium butyricum/*immunology MH - Dendritic Cells/*immunology MH - Disease Models, Animal MH - Humans MH - Immunity, Mucosal MH - Intestinal Mucosa/cytology/*immunology/microbiology MH - Irritable Bowel Syndrome/chemically induced/immunology/*therapy MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Probiotics/*administration & dosage MH - Treatment Outcome MH - Trinitrobenzenesulfonic Acid/toxicity PMC - PMC6767978 OTO - NOTNLM OT - Clostridium butyricum OT - Irritable bowel syndrome OT - Lamina propria dendritic cells OT - Proinflammatory cytokines OT - T cell immunoglobulin and mucin domain-3 COIS- Conflict-of-interest statement: The authors declare no conflicts of interest related to this manuscript or its publication. EDAT- 2019/10/03 06:00 MHDA- 2020/02/27 06:00 PMCR- 2019/09/28 CRDT- 2019/10/03 06:00 PHST- 2019/07/10 00:00 [received] PHST- 2019/08/17 00:00 [revised] PHST- 2019/08/24 00:00 [accepted] PHST- 2019/10/03 06:00 [entrez] PHST- 2019/10/03 06:00 [pubmed] PHST- 2020/02/27 06:00 [medline] PHST- 2019/09/28 00:00 [pmc-release] AID - 10.3748/wjg.v25.i36.5469 [doi] PST - ppublish SO - World J Gastroenterol. 2019 Sep 28;25(36):5469-5482. doi: 10.3748/wjg.v25.i36.5469.