Vitamin C alleviates acute enterocolitis in Campylobacter jejuni infected mice

Soraya Mousavi,Ulrike Escher,Sophie Kittler,Elisa Thunhorst,Markus M Heimesaat,Stefan Bereswill,Corinna Kehrenberg

doi:10.1038/s41598-020-59890-8

Abstract

Human foodborne infections with the zoonotic pathogen Campylobacter jejuni are on the rise and constitute a significant socioeconomic burden worldwide. The health-beneficial, particularly anti-inflammatory effects of vitamin C (ascorbate) are well known. In our preclinical intervention study, we assessed potential anti-pathogenic and immunomodulatory effects of ascorbate in C. jejuni-infected secondary abiotic IL-10−/− mice developing acute campylobacteriosis similar to humans. Starting 4 days prior peroral C. jejuni-infection, mice received synthetic ascorbate via the drinking water until the end of the experiment. At day 6 post-infection, ascorbate-treated mice harbored slightly lower colonic pathogen loads and suffered from less severe C. jejuni-induced enterocolitis as compared to placebo control animals. Ascorbate treatment did not only alleviate macroscopic sequelae of infection, but also dampened apoptotic and inflammatory immune cell responses in the intestines that were accompanied by less pronounced pro-inflammatory cytokine secretion. Remarkably, the anti-inflammatory effects of ascorbate pretreatment in C. jejuni-infected mice were not restricted to the intestinal tract but could also be observed in extra-intestinal compartments including liver, kidneys and lungs. In conclusion, due to the potent anti-inflammatory effects observed in the clinical murine C. jejuni-infection model, ascorbate constitutes a promising novel option for prophylaxis and treatment of acute campylobacteriosis.

Highlights

Human foodborne infections with the zoonotic pathogen Campylobacter jejuni are on the rise and constitute a significant socioeconomic burden worldwide
At day 6 p.i., colonic C. jejuni loads were slightly lower in ascorbate as compared to placebo treated mice, whereas pathogen numbers were comparable in more proximal parts of the gastrointestinal tract including stomach, duodenum and ileum (n.s.; Fig. 1)
The disease-alleviating effects of ascorbate treatment in C. jejuni infected mice were not restricted to the intestinal tract but could be observed in extra-intestinal compartments. In this preclinical intervention study, we addressed for the first time potential anti-pathogenic and immunomodulatory properties of vitamin C during experimental acute campylobacteriosis in a clinical murine infection model

Summary

Introduction

Human foodborne infections with the zoonotic pathogen Campylobacter jejuni are on the rise and constitute a significant socioeconomic burden worldwide. In our preclinical intervention study, we assessed potential anti-pathogenic and immunomodulatory effects of ascorbate in C. jejuni-infected secondary abiotic IL-10−/− mice developing acute campylobacteriosis similar to humans. We could recently show that a depletion of the gastrointestinal microbiota upon broad-spectrum antibiotic application in IL-10−/− mice facilitates intestinal C. jejuni colonization resulting in the development of key symptoms of acute human campylobacteriosis including wasting and bloody diarrhea within several days post-infection[21]. It is known that during phagocytosis, human granulocytes release hydrogen peroxide (H2O2) into the extracellular medium subsequently causing oxidative stress[39] and cell damage by lipid peroxidation and alteration of protein and nucleic acid structure[40] Due to this potent antioxidant property, ascorbate has been shown to neutralize H2O2 and to reduce the H2O2-induced apoptosis in periodontal tissues[41]. Vitamin C (alone or in combination with antibiotics) constitutes a promising treatment option to destabilize bacterial biofilms

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Conclusion