Case Control Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2021; 27(24): 3609-3629
Published online Jun 28, 2021. doi: 10.3748/wjg.v27.i24.3609
Altered profiles of fecal bile acids correlate with gut microbiota and inflammatory responses in patients with ulcerative colitis
Zhen-Huan Yang, Fang Liu, Xiao-Ran Zhu, Fei-Ya Suo, Zi-jun Jia, Shu-Kun Yao
Zhen-Huan Yang, Xiao-Ran Zhu, Fei-Ya Suo, Zi-jun Jia, Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
Zhen-Huan Yang, Fang Liu, Xiao-Ran Zhu, Fei-Ya Suo, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Author contributions: Yang ZH designed and performed the study, analyzed the data, and drafted the manuscript; Liu F and Jia ZJ collected the samples and clinical data of the patients; Zhu XR and Suo FY took part in designing the study and analyzing the data; Yao SK designed the study, supervised the study performance, revised the manuscript, and obtained the funding.
Supported by National Key Technology Support Program during “12th Five-Year Plan” Period of China, No. 2014BAI08B00; National Key Research and Development Plan for Precision Medicine Research, No. 2017YFC0910002; and Leap-forward Development Program for Beijing Biopharmaceutical Industry (G20), No. Z171100001717008.
Institutional review board statement: This study was approved by the Ethics Committee of China-Japan Friendship Hospital (No. 2019-K16).
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, 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, Professor, Department of Gastroenterology, China-Japan Friendship Hospital, No. 2 Yinghua East Street, Chaoyang District, Beijing 100029, China.
Received: February 6, 2021
Peer-review started: February 6, 2021
First decision: March 14, 2021
Revised: March 22, 2021
Accepted: May 25, 2021
Article in press: May 25, 2021
Published online: June 28, 2021
Research background

The gut microbiota and its metabolites are involved in the pathogenesis of inflammatory bowel disease. Bile acid (BA) metabolites have recently drawn much attention in ulcerative colitis (UC). Animal studies have shown that secondary BAs participate in intestinal inflammatory responses via the BA receptors Takeda G-protein-coupled receptor 5 (TGR5) and vitamin D receptor (VDR). However, there are few studies about the quantitative analysis of fecal BAs and intestinal TGR5 and VDR expression in patients with UC. The relationship between BAs and inflammatory cytokines has not been investigated in UC patients. It was hypothesized that BA metabolites may play a role in the pathogenesis of UC.

Research motivation

The main topics of this study included clinical assessments, screening different key gut microbiota and BAs, examining BA receptor expression in UC patients and healthy controls (HCs), performing correlation analyses between these parameters, and clarifying whether there were similar mechanisms to those of animal studies in UC patients. The findings suggested a mechanism by which the gut microbiota and BAs may participate in the pathophysiology of UC and may provide new insights into the management of UC.

Research objectives

The aims of this study were to compare differences in the gut microbiota, fecal BAs, and BA receptor expression in the intestinal mucosa between UC patients and HVs and to analyze the relationship of BAs with the gut microbiota and inflammatory cytokines.

Research methods

The present study used 16S rDNA sequencing technology to detect the differences in the intestinal flora between UC patients and HCs. Fecal BAs were measured by targeted metabolomics approaches. Mucosal TGR5 and VDR expression was analyzed using immunohistochemistry, and serum inflammatory cytokine levels were detected by ELISA.

Research results

It was found that the diversity of gut microbes in UC patients was reduced compared with that in HCs. The concentrations of fecal secondary BAs such as lithochalic acid, deoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, and taurolithocholic acid in UC patients were significantly lower than those in HCs and were positively correlated with Butyricicoccus, Roseburia, Clostridium IV, Faecalibacterium, and Clostridium XlVb. The concentrations of primary BAs such as taurocholic acid, cholic acid, taurochenodeoxycholic acid, and glycochenodeoxycholic acid in UC patients were significantly higher than those in HCs and positively correlated with Enterococcus, Klebsiella, Streptococcus, Lactobacillus and proinflammatory cytokines. The mucosal expression of TGR5 was significantly elevated in UC patients. VDR expression in colonic mucosal specimens was significantly decreased in UC patients.

Research conclusions

Fecal BAs are closely related to the gut microbiota and serum inflammatory cytokines. Dysregulation of the gut microbiota and altered constitution of fecal BAs may participate in regulating inflammatory responses via the BA receptors TGR5 and VDR. These findings not only contribute to the understanding of the role of the gut microbiota and metabolites in UC pathogenesis but also offer a valuable reference for future research and more effective therapies.

Research perspectives

This preliminary study investigated the changes in the fecal BA metabolite profile and analyzed the relationship between metabolites, the gut microbiota, and inflammation in patients with UC. In the future, we will focus on the following aspects. First, due to limited time and conditions, the sample size was relatively small, which may impact the reliability of the conclusion. Second, we cannot draw causal inferences in this cross-sectional study. Therefore, conclusions need to be further verified by well-designed large-sample clinical studies and basic studies. Third, diet was not standardized during the study period. It is necessary to standardize diet in future studies to avoid the influence of diet on the intestinal flora and metabolites.