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

Bile acids (BAs) have attracted attention in the research of irritable bowel syndrome with predominant diarrhea (IBS-D) due to their ability to modulate bowel function and their tight connection with the gut microbiota. The composition of the fecal BA pool in IBS-D patients is reportedly different from that in healthy populations. We hypothesized that BAs may participate in the pathogenesis of IBS-D and the altered BA profile may be correlated with the gut microbiome.


To investigate the role of BAs in the pathogenesis of IBS-D and the correlation between fecal BAs and gut microbiota.


Fifty-five IBS-D patients diagnosed according to the Rome IV criteria and twenty-eight age-, sex-, and body mass index-matched healthy controls (HCs) were enrolled in this study at the gastroenterology department of China-Japan Friendship Hospital. First, clinical manifestations were assessed with standardized questionnaires, and visceral sensitivity was evaluated via the rectal distension test using a high-resolution manometry system. Fecal primary BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), secondary BAs including deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) as well as the corresponding tauro- and glyco-BAs were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry. The gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between fecal BAs with clinical features and gut microbiota were explored.


Fecal CA (IBS-D: 3037.66 [282.82, 6917.47] nmol/g, HC: 20.19 [5.03, 1304.28] nmol/g; P < 0.001) and CDCA (IBS-D: 1721.86 [352.80, 2613.83] nmol/g, HC: 57.16 [13.76, 1639.92] nmol/g; P < 0.001) were significantly increased, while LCA (IBS-D: 1621.65 [58.99, 2396.49] nmol/g, HC: 2339.24 [1737.09, 2782.40]; P = 0.002] and UDCA (IBS-D: 8.92 [2.33, 23.93] nmol/g, HC: 17.21 [8.76, 33.48] nmol/g; P = 0.025) were significantly decreased in IBS-D patients compared to HCs. Defecation frequency was positively associated with CA (r = 0.294, P = 0.030) and CDCA (r = 0.290, P = 0.032) and negatively associated with DCA (r = −0.332, P = 0.013) and LCA (r = −0.326, P = 0.015) in IBS-D patients. In total, 23 of 55 IBS-D patients and 15 of 28 HCs participated in the visceral sensitivity test. The first sensation threshold was negatively correlated with CDCA (r = −0.459, P = 0.028) in IBS-D patients. Furthermore, the relative abundance of the family Ruminococcaceae was significantly decreased in IBS-D patients (P < 0.001), and 12 genera were significantly lower in IBS-D patients than in HCs (P < 0.05), with 6 belonging to Ruminococcaceae. Eleven of these genera were negatively correlated with primary BAs and positively correlated with secondary BAs in all subjects.


The altered metabolism of BAs in the gut of IBS-D patients was associated with diarrhea and visceral hypersensitivity and might be ascribed to dysbiosis, especially the reduction of genera in Ruminococcaceae.

Keywords: Bile acids, Irritable bowel syndrome, Diarrhea, Visceral hypersensitivity, Microbiota, Dysbiosis

Core Tip: This study comprehensively investigated the fecal bile acid profile of irritable bowel syndrome with predominant diarrhea (IBS-D) patients and healthy controls, and the correlations between bile acids (BAs) and clinical characteristics as well as the gut microbiota of IBS-D patients. We found that the composition of fecal BAs in IBS-D patients is featured by increased primary BAs and decreased secondary BAs, which was associated with diarrhea and visceral hypersensitivity. The abnormality of BAs might be induced by dysbiosis in IBS-D patients, especially the reduction of genera in the Ruminococcaceae family, which contains the majority of bacteria that are capable of converting primary BAs into secondary BAs.