Published online Jul 6, 2022. doi: 10.12998/wjcc.v10.i19.6385
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
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).
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.
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.
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.
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.
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.
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.