Vitamin C alleviates acute enterocolitis in Campylobacter jejuni infected mice

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 antiinflammatory 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. jejuniinfection model, ascorbate constitutes a promising novel option for prophylaxis and treatment of acute campylobacteriosis. Campylobacter jejuni are the most common cause of food-borne gastroenteritis with increasing prevalence worldwide 1,2. In fact, human campylobacteriosis represents a socioeconomic burden given estimated disease-associated costs of approximately 2.4 billion Euro 3. Most commonly, C. jejuni transfer via consumption of contaminated raw or undercooked meat and milk or the ingestion of contaminated surface water to humans 4-8. The intestinal colonization of C. jejuni induces a strong inflammatory response of the innate immune system affecting both, absorptive and secretory functions of the gastrointestinal tract 1. In fact, campylobacteriosis constitutes a classical sodium malabsorption syndrome 9 , which depending on the bacterial strain and the host immune status, results in illness of varying degree 10. Whereas some patients remain asymptomatic or display mild symptoms, others develop fever, abdominal pain and watery diarrhea, or suffer from acute campylobacteriosis characterized by severe enterocolitis with inflammatory, bloody diarrhea 1,11. In the majority of events, the disease is self-limited and treated symptomatically, whereas patients with immunosuppressive comorbidities require antibiotic treatment 11,12. However, in few instances, post-infectious sequelae including Guillain-Barré syndrome, Miller Fisher syndrome, reactive arthritis and chronic inflammatory conditions of the intestinal tract might develop with a latent period of weeks or longer 1,13. Even though human campylobacteriosis is becoming increasingly impo...

Vitamin E as promising adjunct treatment option in the combat of infectious diseases caused by bacterial including multi-drug resistant pathogens – Results from a comprehensive literature survey

“…Furthermore, in an acute campylobacteriosis model, vitamin D application could sufficiently dampen pro-inflammatory immune responses upon peroral infection of mice with the enteropathogen Campylobacter jejuni [34]. Besides vitamin D also vitamin C has been proven as potent antimicrobial agent against C. jejuni [40][41][42][43], H. pylori [44,45] and Mycobacterium tuberculosis [46,47]. These findings support the hypothesis that also other vitamins including vitamin E might be promising candidate molecules with antimicrobial modes of action.…”

Immune-modulatory Properties of the Octapeptide NAP in Campylobacter jejuni Infected Mice Suffering from Acute Enterocolitis

“…Secondary abiotic IL-10 −/− mice that had been pre-treated with vitamin C or carvacrol, for instance, harbored lower colonic pathogen loads and were suffering from less severe enterocolitis upon C. jejuni infection as compared to placebo control animals. Additionally, these treatment regimens dampened apoptotic epithelial and pro-inflammatory immune cell responses in the intestines that were accompanied by less pronounced pro-inflammatory cytokine secretion [19,20]. Potent immune-modulatory properties during acute C. jejuni induced enterocolitis could also be achieved by peroral application of vitamin D starting before C. jejuni infection [18].…”

Novel Clinical Campylobacter jejuni Infection Models Based on Sensitization of Mice to Lipooligosaccharide, a Major Bacterial Factor Triggering Innate Immune Responses in Human Campylobacteriosis

“…Most recently, the secondary abiotic IL10 deficient murine model of campylobacteriosis was standardized and could be developed to the preclinical level for pharmaceutical analysis of alternative drugs, including ascorbate and vitamin D, which effectively suppressed C. jejuni-induced inflammation in the course of campylobacteriosis [20,160].…”

“…Depending on the Campylobacter strain and the host immune status, patients might present with a highly acute and severe symptom complex varying from watery diarrhea without fever and/or abdominal cramps to severe campylobacteriosis characterized by purulent bloody inflammatory diarrhea and systemic inflammatory responses including fever [9,[16][17][18]. The infection is usually self-limiting and lasts for several days to two weeks [19,20]. However, in the minority of cases, post-infectious sequelae such as Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS), reactive arthritis (RA) or chronic intestinal inflammatory morbidities including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) or celiac disease might develop [4,9,18,[21][22][23].…”