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

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 irritable bowel syndrome (IBS). However, the metabolic profile and pathophysiology of IBS are still unclear. We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea (IBS-D).


To investigate the fecal metabolite composition and the role of metabolites in IBS-D pathophysiology.


Thirty IBS-D patients and 15 age- and sex-matched healthy controls (HCs) underwent clinical and psychological assessments, including the IBS Symptom Severity System (IBS-SSS), an Italian modified version of the Bowel Disease Questionnaire, the Bristol Stool Form Scale (BSFS), the Hospital Anxiety and Depression Scale, and the Visceral Sensitivity Index. Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator. Fecal metabolites, including amino acids and organic acids, were measured by targeted metabolomics approaches. Correlation analyses between these parameters were performed.


The patients presented with increased stool water content, more psychological symptoms and increased visceral hypersensitivity compared with the controls. In fecal metabolites, His [IBS-D: 0.0642 (0.0388, 0.1484), HC: 0.2636 (0.0780, 0.3966), P = 0.012], Ala [IBS-D: 0.5095 (0.2826, 0.9183), HC: 1.0118 (0.6135, 1.4335), P = 0.041], Tyr [IBS-D: 0.1024 (0.0173, 0.4527), HC: 0.5665 (0.2436, 1.3447), P = 0.018], Phe [IBS-D: 0.1511 (0.0775, 0.3248), HC: 0.3967 (0.1388, 0.7550), P = 0.028], and Trp [IBS-D: 0.0323 (0.0001, 0.0826), HC: 0.0834 (0.0170, 0.1759), P = 0.046] were decreased in IBS-D patients, but isohexanoate [IBS-D: 0.0127 (0.0060, 0.0246), HC: 0.0070 (0.0023, 0.0106), P = 0.028] was significantly increased. Only Tyr was mildly correlated with BSFS scores in all subjects (r = -0.347, P = 0.019). A possible potential biomarker panel was identified to correlate with IBS-SSS score (R2Adjusted = 0.693, P < 0.001). In this regression model, the levels of Tyr, Val, hexanoate, fumarate, and pyruvate were significantly associated with the symptom severity of IBS-D. Furthermore, visceral sensation, including abdominal pain and visceral hypersensitivity, was correlated with isovalerate, valerate and isohexanoate.


Altered profiles of fecal metabolites may be one of the origins or exacerbating factors of symptoms in IBS-D via increasing visceral sensitivity.

Keywords: Fecal metabolite, Irritable bowel syndrome, Amino acids, Organic acids, Short chain fatty acids, Visceral hypersensitivity

Core tip: We comprehensively assessed the clinical and psychological characteristics of irritable bowel syndrome with predominant diarrhea (IBS-D) , visceral sensitivity, and fecal metabolites. As expected, the data confirmed that metabolite compositions were different in subjects with or without IBS-D and the levels of some metabolites were significantly correlated with IBS Symptom Severity System score, visceral sensitivity, and the severity or frequency of abdominal pain. Furthermore, a potential biomarker panel was identified to correlate with the symptom severity of IBS-D. These preliminary findings provide some clues for IBS-D pathogenesis and for the search for biomarkers in symptom severity.