Case Control Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 6, 2022; 10(19): 6385-6398
Published online Jul 6, 2022. doi: 10.12998/wjcc.v10.i19.6385
Intestinal mucosal barrier in functional constipation: Dose it change?
Jun-Ke Wang, Wei Wei, Dong-Yan Zhao, Hui-Fen Wang, Yan-Li Zhang, Jie-Ping Lei, Shu-Kun Yao
Jun-Ke Wang, Dong-Yan Zhao, Shu-Kun Yao, Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Jun-Ke Wang, Dong-Yan Zhao, Hui-Fen Wang, Yan-Li Zhang, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Wei Wei, Department of Clinical Nutrition and Department of Health Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
Jie-Ping Lei, Data and Project Management Unit, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
Author contributions: Wang JK designed and performed the study, analyzed the data, and drafted the manuscript; Wei W, Zhao DY, Wang HF, and Zhang YL collected the clinical data and samples from subjects; Lei JP contributed to the study design and data analysis; Yao SK designed the study, supervised the study performance, revised the manuscript, and obtained the funding; all authors read and approved the final manuscript.
Supported by the National Key Technology Support Program during “12th Five-Year Plan” Period of China, No. 2014BAI08B00; 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: The 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shu-Kun Yao, MD, PhD, Doctor, Professor, Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences; Department of Gastroenterology, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Chaoyang District, Beijing 100029, China. shukunyao@126.com
Received: February 1, 2022
Peer-review started: February 1, 2022
First decision: March 15, 2022
Revised: March 21, 2022
Accepted: April 9, 2022
Article in press: April 9, 2022
Published online: July 6, 2022
Processing time: 142 Days and 19.1 Hours
ARTICLE HIGHLIGHTS
Research background

The intestinal mucosal barrier prevents potentially harmful substances in the intestinal lumen from passing through the epithelium to the underlying tissue while allowing the selective absorption and secretion of nutrients and fluids. Disruption of this barrier alters intestinal permeability and activates the immune system in some chronic intestinal disorders. However, no studies have thoroughly explored the intestinal mucosal barrier in patients with functional constipation (FC).

Research motivation

The integrity of the intestinal mucosal barrier contributes to the maintenance of normal intestinal permeability and inner homeostasis. Few studies have investigated this barrier in FC patients. The main experimental procedures of the present study were as follows: counting the goblet cells, CD3+ intraepithelial lymphocytes (IELs) and CD3+ lamina propria lymphocytes in the colonic mucosa in FC patients and healthy controls, observing the ultrastructure of intercellular junctional complexes in FC patients, evaluating the expression of occludin and zonula occludens-1 (ZO-1), and analyzing serum D-lactic acid and zonulin levels in FC patients and healthy controls. These findings may provide the first comprehensive insights into the alterations of the intestinal mucosal barrier in FC patients.

Research objectives

The present study aimed to comprehensively investigate the intestinal mucosal barrier in FC patients, including the mucus barrier, intercellular junctions, mucosal immunity and gut permeability.

Research methods

Subjects underwent colonoscopy and colonic mucosal biopsy. Goblet cells were stained with Alcian Blue/Periodic acid Schiff (AB/PAS) and counted. The ultrastructure of intercellular junctional complexes was observed under an electron microscope. Occludin and ZO-1 in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Colonic CD3+ IELs and CD3+ lymphocytes in the lamina propria were identified and counted using immunofluorescence. The serum levels of D-lactic acid and zonulin were assayed using enzyme-linked immunosorbent assay.

Research results

Compared to healthy controls, the staining of mucus secreted by goblet cells was darker and the number of goblet cells in the colonic mucosa was significantly increased in FC patients. The intercellular junctional complexes in the colonic epithelium were integral in FC patients. There were no significant alterations in the localization, protein and mRNA expression of occludin and ZO-1 in the colonic mucosa in FC patients compared to healthy controls. No significant differences were observed in the number of CD3+ IELs and CD3+ lamina propria lymphocytes between the two groups. There were no significant differences in serum D-lactic acid or zonulin levels between FC patients and healthy controls.

Research conclusions

This study provides the first comprehensive evidence that the intestinal mucosal barrier in FC patients shows a compensatory increase in mucus production and secretion as well as integral intercellular junctional complexes in the colonic epithelium without activation of mucosal immunity or increased gut permeability.

Research perspectives

The present study thoroughly investigated the key components of the intestinal mucosal barrier in FC patients. In the future, the molecular mechanisms underlying the alterations of this barrier, such as the interaction between gut microbiota in FC patients and the mucosal barrier, need to be explored. Further studies should also evaluate the intestinal barrier in FC patients from a functional level.