Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2020; 26(45): 7153-7172
Published online Dec 7, 2020. doi: 10.3748/wjg.v26.i45.7153
Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome
Wei Wei, Hui-Fen Wang, Yu Zhang, Yan-Li Zhang, Bing-Yu Niu, Shu-Kun Yao
Wei Wei, Yu Zhang, Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Wei Wei, Hui-Fen Wang, Yu Zhang, Yan-Li Zhang, Bing-Yu Niu, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Bing-Yu Niu, Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
Author contributions: Wei W designed and performed the study, analyzed the data, and drafted the manuscript; Wei W, Wang HF, Zhang YL, and Niu BY collected the clinical data and fecal samples from subjects; Zhang Y gave guidance on experiment operation and data interpretation, and contributed to manuscript revision; Yao SK designed the study, supervised the study performance, revised the manuscript, and obtained the funding.
Supported by the National Key Technology Support Program during “12th Five-Year Plan” Period of China, No. 2014BAI08B00; the Leap-forward Development Program for Beijing Biopharmaceutical Industry (G20), No. Z171100001717008; and the Project “The role of the gut microbiota and metabolites in the pathogenesis of diarrhea-predominant irritable bowel syndrome” of China-Japan Friendship Hospital, No. 2019-64-K44.
Institutional review board statement: This study was approved by the Ethics Committee of China-Japan Friendship Hospital (No. 2019-64-K44).
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: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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, No. 2 Yinghua East Street, Chaoyang District, Beijing 100029, China.
Received: August 17, 2020
Peer-review started: August 17, 2020
First decision: September 12, 2020
Revised: September 21, 2020
Accepted: October 13, 2020
Article in press: October 13, 2020
Published online: December 7, 2020
Research background

Bile acids (BAs) have attracted attention in irritable bowel syndrome with predominant diarrhea (IBS-D) because of the effects on gastrointestinal motility and secretion function of the intestine. Experiments in animals and healthy volunteers also indicated that hypersensitivity can be caused by BAs, which is a major patho-physiological abnormality in IBS-D. The metabolism of BAs in the intestine depends on the gut microbiota. Therefore, it could be hypothesized that BAs may be involved in the pathogenesis of IBS-D and the altered BA profile in the intestine may be associated with microbiota.

Research motivation

Although a few studies have portrayed the composition of fecal BAs in IBS-D patients, the data in Chinese IBS-D patients are still sparse. Besides, few studies have explored the correlations between the gut flora and BAs in IBS-D patients. The main topics of this study included identifying the correlations of BAs with clinical features containing rectoanal sensory parameters of IBS-D patients, and exploring the correlations between the composition of fecal BAs and the gut microbiome. The findings may add insight to the pathogenesis of IBS-D, and provide evidence for regulating intestinal BAs to treat IBS-D.

Research objectives

The present study aimed to evaluate the correlations of BAs with clinical features of IBS-D patients and to explore whether the composition of fecal BAs was associated with the gut microbiome in IBS-D patients.

Research methods

Subjects underwent clinical and psychological assessments, including IBS symptom severity system, the grade of Bristol stool form scale and defecation frequency per day in the preceding 2 wk, hospital anxiety and depression scale, and visceral sensitivity index, along with visceral sensitivity testing with a high-resolution manometry system. Fecal BAs were measured by ultraperformance liquid chromatography coupled to tandem mass spectrometry. The gut microbiota was analyzed using 16S rRNA gene sequencing. Relationships between fecal BAs and clinical characteristics as well as gut microbiota were explored.

Research results

Cholic acid, chenodeoxycholic acid (CDCA), and their conjugated BAs were significantly increased, while lithocholic acid (LCA) and ursodeoxycholic acid were significantly decreased and deoxycholic acid (DCA) tended to decrease in IBS-D patients. Defecation frequency was positively associated with primary BAs and inversely associated with DCA and LCA in IBS-D patients. The first sensation threshold was negatively correlated, and the defecating sensation threshold tended to be negatively correlated with CDCA in IBS-D patients. Furthermore, several genera were significantly reduced in IBS-D patients compared with HCs and exhibited a negative correlation with primary BAs and a positive correlation with secondary BAs, especially the genera in the Ruminococcaceae family.

Research conclusions

This study presented evidence that the composition of the fecal BA pool was characterized by increased primary BAs and decreased secondary BAs in IBS-D, which was associated with diarrhea and visceral hypersensitivity in IBS-D. The dysmetabolism of BAs in IBS-D might be ascribed to gut dysbiosis especially the reduction of Ruminococcaceae.

Research perspectives

In the future, careful evaluation of the usual dietary habit of subjects is required, and diet needs to be standardized during the study period. Large multicenter studies are also necessary to verify the conclusions drawn in this study. Notably, BA sequestrant may contribute to the studies on the involvement of BAs in IBS-D pathophysiology as well as the association between BAs and microbiota.