Oral application of carvacrol, butyrate, ellagic acid, and 2'-fucosyl-lactose to mice suffering from acute campylobacteriosis - Results from a preclinical placebo-controlled intervention study.

Background: Acute campylobacteriosis caused by oral infections with the enteropathogen Campylobacter jejuni represent serious threats to global human health. Since novel treatment options with safe and antibiotics-independent compounds would be highly appreciable, we here investigated the anti-bacterial and disease-alleviating effects of carvacrol, butyrate, ellagic acid, and 2'-fucosyl-lactose in acute murine campylobacteriosis. To address this, secondary abiotic IL-10-/- mice were perorally infected with C. jejuni and treated with either compound alone or all four in combination via the drinking water starting two days post-infection. Results: On day 6, the duodenal pathogen loads were lower in mice of the combination versus the vehicle treatment cohort. Importantly, mice treated with carvacrol and the combination presented with less distinct diarrheal symptoms, colonic histopathology, epithelial cell apoptosis, and immune cell responses when compared to vehicle counterparts on day 6 post-infection. Furthermore, the combination treatment did not only diminish colonic IFN-γ, TNF-α, and IL-6 secretion in C. jejuni infected mice, but also dampened extra-intestinal and even systemic pro-inflammatory cytokine concentrations to basal levels as measured in liver, kidneys, lungs, and serum samples. Conclusions: Our preclinical placebo-controlled intervention trial provides evidence that the combined oral application of carvacrol, butyrate, ellagic acid, and 2'-fucosyl-lactose alleviates acute campylobacteriosis in the vertebrate host.