Resveratrol Prevents Campylobacter jejuni-Induced Leaky gut by Restoring Occludin and Claudin-5 in the Paracellular Leak Pathway

Abstract

Campylobacter jejuni is a bacterial human pathogen causing gastroenteritis and sequelae like irritable bowel syndrome. Epidemiologists count the human campylobacteriosis by C. jejuni as the most common foodborne zoonosis and bacterial diarrheal disease worldwide. Based on bioinformatics predictions for potential protective compounds in campylobacteriosis, the question was raised whether the plant-based polyphenol resveratrol is sufficient to attenuate intestinal epithelial damage induced by C. jejuni. We investigated this by performing experimental infection studies in an epithelial cell culture and the secondary abiotic IL-10−/− mouse model. In C. jejuni-infected human colonic HT-29/B6 cell monolayers, transepithelial electrical resistance (TER) was decreased and the paracellular marker flux of fluorescein (332 Da) increased. Concomitantly, the tight junction (TJ) proteins occludin and claudin-5 were re-distributed off the tight junction domain. This was accompanied by an increased induction of epithelial apoptosis, both changes contributing to compromised barrier function and the opening of the leak pathway induced by C. jejuni. In parallel, the recovery experiments with the application of resveratrol revealed a functional improvement of the disturbed epithelial barrier in both models in vitro and in vivo. During treatment with resveratrol, TJ localization of occludin and claudin-5 was fully restored in the paracellular domain of HT-29/B6 cells. Moreover, resveratrol decreased the rate of epithelial apoptosis. These resveratrol-induced molecular and cellular effects would therefore be expected to improve epithelial barrier function, thereby minimizing the so-called leaky gut phenomenon. In conclusion, the induction of the leak pathway by C. jejuni and the restoration of barrier function by resveratrol demonstrates its effectiveness as a potential preventive or therapeutic method of mitigating the leaky gut associated with campylobacteriosis.

Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

“…Nevertheless, administration of the pre-hormone VD protects against C. jejuni-induced epithelial barrier dysfunction in vitro and in vivo. VD should therefore be considered as a potentially useful therapeutic supplement, when combined with other barrier-protective, immunomodulatory, and anti-inflammatory compounds, such as curcumin or resveratrol [3,45,46], for prevention and treatment of acute and chronic gastrointestinal disorders.…”

Intestinal Barrier in Post-Campylobacter jejuni Irritable Bowel Syndrome

“…Some of these have also been shown to be effective in IBS. They did not show an anti-microbial effect, but rather an immunomodulatory and barrier-stabilizing effect, such as the polyphenols curcumin or resveratrol or the hormone vitamin D (calcitriol) [ 6 , 7 , 8 ]. In addition, vitamin D has been reported to protect against macromolecule influx into C. jejuni -infected intestinal epithelial cells and against bacterial translocation [ 8 ].…”

“…Natural compounds have been identified that may combat C. jejuni infection by enhancing barrier function and down-regulating immune activation, namely the polyphenols resveratrol and curcumin, and the pre-hormone vitamin D [ 6 , 7 , 8 ]. Complementary intervention strategies of this type are conceivable for acute infections, but could also be useful for oral use in the recovery phase of an infection or afterwards for the prevention of PI-IBS.…”

Intervention of Shugan Xiaozhi Decoction on Nonalcoholic Fatty Liver Disease via Mediating Gut-Liver Axis

“…Tight junction proteins, ZO-1 and occludin, play an important role in maintaining the monolayer integrity of intestinal epithelial cells [ 54 ]. ZO-1 is a cytoplasmic plaque protein that connects transmembrane protein and cytoskeleton, while occludin can affect the tight junction of intestinal epithelial cells by regulating macromolecular flux, both of which are indicator of mucosal integrity, and decreased expression indicates impaired barrier integrity [ 55 , 56 ]. In our results, the expression of ZO-1 and occludin in the intestinal tract of NAFLD rats was significantly reduced but increased after SX intervention, suggesting that SX could repair the intestinal barrier by increasing the expression of ZO-1 and occludin, which was consistent with the above conclusion.…”