Resveratrol Alleviates Acute Campylobacter jejuni Induced Enterocolitis in a Preclinical Murine Intervention Study.

Markus M Heimesaat,Elisa Peh,Sophie Kittler,Stefan Bereswill,Roland Bücker,Jörg-Dieter Schulzke,Ulrike Escher,Soraya Mousavi,Fábia Daniela Lobo De Sá

doi:10.3390/microorganisms8121858

Abstract

The polyphenolic compound resveratrol has been shown to exert health-beneficial properties. Given globally emerging Campylobacter infections in humans, we addressed potential anti-pathogenic, immuno-modulatory and intestinal epithelial barrier preserving properties of synthetic resveratrol in the present preclinical intervention study applying a murine acute campylobacteriosis model. Two days following peroral C. jejuni infection, secondary abiotic IL-10−/− mice were either subjected to resveratrol or placebo via the drinking water. Whereas placebo mice suffered from acute enterocolitis at day 6 post-infection, resveratrol treatment did not only lead to improved clinical conditions, but also to less pronounced colonic epithelial apoptosis as compared to placebo application. Furthermore, C. jejuni induced innate and adaptive immune cell responses were dampened in the large intestines upon resveratrol challenge and accompanied by less colonic nitric oxide secretion in the resveratrol versus the placebo cohort. Functional analyses revealed that resveratrol treatment could effectively rescue colonic epithelial barrier function in C. jejuni infected mice. Strikingly, the disease-alleviating effects of resveratrol could additionally be found in extra-intestinal and also systemic compartments at day 6 post-infection. For the first time, our current preclinical intervention study provides evidence that peroral resveratrol treatment exerts potent disease-alleviating effects during acute experimental campylobacteriosis.

Highlights

Campylobacter infections are emerging worldwide and cause tremendous health burdens and socioeconomic costs, irrespective whether low, middle- or high-income countries are concerned [1,2]
In our recent study we showed that resveratrol treatment could ameliorate acute small intestinal inflammation by down-regulating T helper-1 (Th-1) cell immune responses following peroral Toxoplasma gondii infection
Following peroral infection with 109 viable C. jejuni strain 81-176 cells on d0 and d1, the pathogen could stably establish within the intestinal tract of secondary abiotic IL-10−/− mice from either cohort as indicated by median fecal loads of approximately 109 CFU per g (Supplementary Figure S2)

Summary

Introduction

Campylobacter infections are emerging worldwide and cause tremendous health burdens and socioeconomic costs, irrespective whether low-, middle- or high-income countries are concerned [1,2]. Among the Campylobacter genus, C. jejuni are the most prevalent species causing human illnesses [2]. The enteropathogens might be transferred to humans, following ingestion of contaminated undercooked meat or surface water [3,4]. Following successful passage of the stomach, adhesion to and invasion of the intestinal epithelia by C. jejuni, innate and adaptive immune cells are recruited to the colonic mucosa and lamina propria. Pro-inflammatory mediator secretion leads to oxidative stress to and apoptosis of colonic epithelial cells mounting in epithelial barrier dysfunction [5,6]

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Conclusion