Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2019; 25(36): 5469-5482
Published online Sep 28, 2019. doi: 10.3748/wjg.v25.i36.5469
Clostridium butyricum alleviates intestinal low-grade inflammation in TNBS-induced irritable bowel syndrome in mice by regulating functional status of lamina propria dendritic cells
Qin Zhao, Wen-Rong Yang, Xiao-Hong Wang, Gai-Qin Li, Lei-Qi Xu, Xiao Cui, Yang Liu, Xiu-Li Zuo
Qin Zhao, Lei-Qi Xu, Xiao Cui, Xiu-Li Zuo, Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
Qin Zhao, Xiao-Hong Wang, Gai-Qin Li, Department of Gastroenterology, Taian City Central Hospital, Taian 271000, Shandong Province, China
Wen-Rong Yang, Department of Clinical Nutrition, Taian City Central Hospital, Taian 271000, Shandong Province, China
Yang Liu, Department of Medicine, Beijing 316 Hospital, Beijing 100093, China
Author contributions: Zhao Q, Zuo XL and Xu LQ formulated the study concept, designed the study, and guaranteed the integrity of the entire study; Zhao Q and Cui X contributed to experimental studies and data acquisition; Zhao Q, Cui X, and Xu LQ contributed to literature research and manuscript editing; Zhao Q contributed to definition of intellectual content and clinical studies and manuscript preparation; Zhao Q, Cui X, Wang XH, and Yang WR contributed to data analysis; Zhao Q, Cui X, Wang XH, Li GQ, and Liu Y contributed to statistical analysis; Zuo XL and Xu LQ contributed to manuscript review; all authors approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81770538 and No. 81570485; and Key Research and Development Program of Shandong Province, No. 2017CXGC1215.
Institutional animal care and use committee statement: This study was approved by the Institutional Animal Ethical Review Board of Taian City Central Hospital.
Conflict-of-interest statement: The authors declare no conflicts of interest related to this manuscript or its publication.
ARRIVE guidelines statement: The ARRIVE Guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xiu-Li Zuo, MD, PhD, Associate Professor, Chief Doctor, Department of Gastroenterology, Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong Province, China.
Telephone: +86-531-88369277 Fax: +86-531-88369277
Received: July 10, 2019
Peer-review started: July 10, 2019
First decision: August 5, 2019
Revised: August 17, 2019
Accepted: August 24, 2019
Article in press: August 24, 2019
Published online: September 28, 2019

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-1β, 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.


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.


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-1β 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.


The secretion of proinflammatory cytokines (IL-1β 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-1β 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.


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.

Keywords: Clostridium butyricum, Irritable bowel syndrome, Lamina propria dendritic cells, T cell immunoglobulin and mucin domain-3, Proinflammatory cytokines

Core tip: In this study, we revealed that Clostridium butyricum can regulate the number and functional status of lamina propria dendritic cells in the intestinal mucosa of mice with irritable bowel syndrome, and therefore modulate the local immune response in the intestine.