Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2017; 23(47): 8321-8333
Published online Dec 21, 2017. doi: 10.3748/wjg.v23.i47.8321
Fructo-oligosaccharide intensifies visceral hypersensitivity and intestinal inflammation in a stress-induced irritable bowel syndrome mouse model
Bin-Rui Chen, Li-Jun Du, Hui-Qin He, John J Kim, Yan Zhao, Ya-Wen Zhang, Liang Luo, Ning Dai
Bin-Rui Chen, Li-Jun Du, Hui-Qin He, Ya-Wen Zhang, Liang Luo, Ning Dai, Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
John J Kim, Yan Zhao, Division of Gastroenterology, Loma Linda University Medical Center, Loma Linda, CA 92354, United States
Author contributions: All authors contributed to the design of the study; Chen BR, Du LJ, He HQ, Zhang YW and Luo L performed the experiments; Chen BR and Du LJ analyzed the data; Chen BR, Kim JJ and Zhao Y wrote the paper; Kim JJ and Dai N critically revised the manuscript; All authors have reviewed the manuscript and given advice.
Institutional review board statement: The study was reviewed and approved by Zhejiang University Animal Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Zhejiang University.
Conflict-of-interest statement: The authors declare no conflict of interest related to this study.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ning Dai, MD, PhD, Department Chief, Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, No. 3, East Qingchun Road, Hangzhou 310016, Zhejiang Province, China. ndaicn@zju.edu.cn
Telephone: +86-571-86044817 Fax: +86-571-86044817
Received: September 28, 2017
Peer-review started: September 28, 2017
First decision: October 17, 2017
Revised: November 14, 2017
Accepted: November 21, 2017
Article in press: November 21, 2017
Published online: December 21, 2017
Processing time: 83 Days and 18.5 Hours
ARTICLE HIGHLIGHTS
Research background

The impact of dietary factors in exacerbating symptoms of irritable bowel syndrome (IBS) is being increasingly recognized. Specifically, abdominal pain following the consumption of Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) is common, and dietary restriction of FODMAP improves symptoms of IBS.

Research motivation

Although osmotic effects of poorly absorbed carbohydrates and increased colonic gas production from intestinal fermentation are proposed, evidence providing specific mechanism of FODMAP-induced IBS symptoms is sparse. With wide acceptance of low-FODMAP diet as a treatment for IBS, clarifying the specific mechanism is important for optimal application in clinical practice.

Research objectives

The aim of the study was to explore the effects of high-dose fructo-oligosaccharides (FOS), a component of FODMAP, on visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids (SCFA) using an IBS mouse model. FOS administration intensified visceral hypersensitivity and gut inflammation already present in the stress-induced IBS mice, but not in the control mice, and was also associated with increased cecal SCFA production. The results provide a biologic framework for FODMAP-induced IBS symptoms that supports the application of low FODMAP therapy in clinical practice.

Research methods

The effects of FOS on visceral sensitivity, SCFA production, and intestinal inflammation were examined by using a water avoidance stress (WAS)-induced IBS mouse model. Mice were randomly assigned to receive daily WAS or sham-WAS for 10 d while receiving daily oral gavage of saline solution with or without high-dose FOS. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was measured by histologic analyses. Furthermore, intestinal SCFA production, cytokine expression, and mast cell counts were evaluated.

Research results

FOS administration intensified visceral hypersensitivity, increased mucosal mast cell counts, and mediated intestinal cytokine expression in the stressed-induced IBS mice, but not in the control mice. A parallel increase in cecal SCFA levels was also observed with FOS administration in the IBS mice but not in the control mice. These findings suggest that visceral hypersensitivity and gut inflammation intensified by FODMAP diet may lead to worsening IBS symptoms. Examining the effects of other FODMAP components other than FOS on visceral hypersensitivity and immune activation, as well as, detailed molecular mechanism may be invaluable in future studies.

Research conclusions

Administration of high-dose FOS, a component of FODMAP, intensified visceral sensitivity and intestinal inflammation in a stress-induced IBS mouse model, and was also associated with increased production of SCFA. These findings suggest a mechanism of FODMAP-induced gastrointestinal symptoms specific to IBS and are consistent with clinical studies that demonstrate the efficacy of low-FODMAP diet in treatment of individuals with IBS.

Research perspectives

The importance of dietary factors in triggering symptoms is increasingly being recognized in patients with IBS. FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, and is also associated with increased intestinal SCFA production.