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
Abstract
AIM

To determine whether fructo-oligosaccharide (FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids (SCFA) in an irritable bowel syndrome (IBS) mouse model.

METHODS

Mice were randomly assigned to daily oral gavage of saline solution with or without FOS (8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress (WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field (HPF), respectively.

RESULTS

Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid (2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid (0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid (0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA (3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin (IL)-23 mRNA (4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1β mRNA (2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum (12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon (6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS.

CONCLUSION

FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production.

Keywords: Fructo-oligosaccharide, Stress, Irritable bowel syndrome, Visceral hypersensitivity, Intestinal inflammation, Short chain fatty acids, FODMAP

Core tip: Fructo-oligosaccharide is a component of Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP), which has been associated with triggering symptoms in patients with irritable bowel syndrome (IBS). In a stress-induced IBS mouse model, daily fructo-oligosaccharide (FOS) administration further intensified visceral hypersensitivity and low-grade intestinal inflammation compared to saline. FOS administration also led to increased intestinal production of individual and total short-chain fatty acids (SCFA) in mice subjected to stress. However, no difference in visceral sensitivity, intestinal inflammation, or cecal concentrations of SCFA was observed among sham-stressed mice receiving FOS or saline. Our findings suggest a mechanism of FODMAP-induced gastrointestinal symptoms associated with increased production of SCFA specific to IBS.