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
Research background

Irritable bowel syndrome (IBS) affects 7% to 21% of the general population. It is a chronic 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 mechanism has not been clearly elucidated.

Research motivation

To test the hypothesis that the function of dendritic cells (DCs) changes in the development of IBS and to understand the regulation of DCs after C. butyricum intervention.

Research objectives

We aimed to investigate the mechanism of DCs in the development of IBS in a mice model and to understand the regulation of DCs after C. butyricum intervention.

Research 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 test and hematoxylin & eosin staining, respectively. The expression of proinflammatory cytokines (IL-1β and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. The flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the LPDCs. The regulatory effect of C. butyricum was verified in BMDCs by in vitro experiments.

Research results

We found that the IBS mouse model has abundant expression of IL-1β, IL-6, and CD11C+CD80+ and CD11c+TIM3+ LPDCs compared with the control group. Further investigation showed that probiotic C. butyricum reduced the expression of cytokines (IL-1β and IL-6). The amount and function of LPDCs and the membrane molecule TIM3 of the LPDCs were decreased with the alleviation of the intestinal inflammatory response.

Research conclusions

This study demonstrated that C. butyricum could induce the expression of various pro-inflammatory cytokines via regulating the amount and the functional status of LPDCs in the intestinal mucosa of mice with IBS.

Research perspectives

This research not only provides an in-depth understanding of the local immune response mechanism in intestinal mucosa of IBS humans, but also provides a new perspective for the application of probiotic C. butyricum in the treatment of IBS.