Case Control Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2019; 25(43): 6416-6429
Published online Nov 21, 2019. doi: 10.3748/wjg.v25.i43.6416
Altered profiles of fecal metabolites correlate with visceral hypersensitivity and may contribute to symptom severity of diarrhea-predominant irritable bowel syndrome
Wen-Xue Zhang, Yu Zhang, Geng Qin, Kai-Min Li, Wei Wei, Su-Yun Li, Shu-Kun Yao
Wen-Xue Zhang, Yu Zhang, Geng Qin, Wei Wei, Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Wen-Xue Zhang, Yu Zhang, Geng Qin, Wei Wei, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Kai-Min Li, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
Su-Yun Li, Department of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao 266071, Shandong Province, China
Author contributions: Zhang WX designed and performed the study, analyzed the data and drafted the manuscript; Zhang Y, Qin G and Wei W collected material and clinical data from patients; Li KM gave guidance and support on experimental procedure and data interpretation; Li SY contributed to design of the study and analysis of data; Yao SK designed the study, supervised the study performance, revised the manuscript, and obtained the funding.
Supported by the National Key Technology Support Program for the “12th Five-Year Plan” of China, No. 2014BAI08B00; and the Research Projects on Biomedical Transformation of China-Japan Friendship Hospital, No. PYBZ1815.
Institutional review board statement: This study was approved by the Ethics Committee of China-Japan Friendship Hospital, Beijing, China.
Informed consent statement: All study participants provided written informed consent prior to study enrollment.
Conflict-of-interest statement: All authors report no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the first author at
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE Statement.
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: Shu-Kun Yao, MD, PhD, Professor, Department of Gastroenterology, China-Japan Friendship Hospital, 2nd Yinghua East Road, Chaoyang District, Beijing 100029, China.
Telephone: +86-10-84205108 Fax: +86-10-84205108
Received: September 19, 2019
Peer-review started: September 19, 2019
First decision: October 14, 2019
Revised: October 19, 2019
Accepted: November 1, 2019
Article in press: November 1, 2019
Published online: November 21, 2019
Research background

Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder and the pathogenesis is complicated. Fecal metabolites are associated with gut visceral sensitivity, mucosal immune function and intestinal barrier function, all of which have critical roles in the pathogenesis of IBS.

Research motivation

A few articles reported that patients diagnosed with IBS had metabolite compositions that were different from those of healthy controls. However, the role of metabolites in IBS pathophysiology is unclear. The study of fecal metabolites might add insight to investigate IBS.

Research objectives

IBS with predominant diarrhea (IBS-D) is the major subtype of IBS. The aims of this study were to compare fecal metabolites in subjects with or without IBS-D and to explore the associations of metabolites with clinical and experimental parameters.

Research methods

Participants underwent clinical and psychological assessments, including the IBS Symptom Severity System, an Italian modified version of the Bowel Disease Questionnaire, the Bristol Stool Form Scale, the Hospital Anxiety and Depression Scale, and the VSI, along with visceral sensitivity testing. Fecal metabolites were measured by targeted metabolomics approaches. Correlation analyses between these parameters were performed. SPSS (IBM-SPSS Statistics, Chicago, IL, United States) version 21.0 was used for statistical analysis.

Research results

The patients presented with more psychological symptoms and increased visceral hypersensitivity compared with the controls. In fecal metabolites, His, Ala, Tyr, Phe, and Trp were decreased in IBS-D patients, but isohexanoate was increased. Abdominal pain or visceral hypersensitivity was correlated with isovalerate, valerate and isohexanoate. Furthermore, a significant correlation was observed between metabolites and symptom severity.

Research conclusions

This study presented evidence that metabolite compositions were different in subjects with or without IBS-D and some metabolites might be one of the origins or exacerbating factors of symptoms via increasing visceral sensitivity. This study also demonstrated a possible potential biomarker panel of symptom severity. The authors believe that this study provides some clues for IBS-D pathogenesis and for the search for biomarkers in symptom severity.

Research perspectives

This preliminary study investigated the possible role of fecal metabolites in IBS pathophysiology. In the future, we will focus on the following aspects. First, as the present study did not standardize diet and could not make cause and effect inferences, conclusions need to be further verified by additional well-designed clinical and basic studies. Second, the present study focused on IBS-D patients, and the conclusions may not be generalized to other IBS subtypes. We will investigate the role of fecal metabolites in pathophysiology of other IBS subtypes in future studies.