Immune-Modulatory Effects upon Oral Application of Cumin-Essential-Oil to Mice Suffering from Acute Campylobacteriosis

Abstract

Human campylobacteriosis, commonly caused by Campylobacter jejuni, is a food-borne infection with rising prevalence causing significant health and socioeconomic burdens worldwide. Given the threat from emerging antimicrobial resistances, the treatment of infectious diseases with antibiotics-independent natural compounds is utmost appreciated. Since the health-beneficial effects of cumin-essential-oil (EO) have been known for centuries, its potential anti-pathogenic and immune-modulatory effects during acute experimental campylobacteriosis were addressed in the present study. Therefore, C. jejuni-challenged secondary abiotic IL-10-/- mice were treated perorally with either cumin-EO or placebo starting on day 2 post-infection. On day 6 post-infection, cumin-EO treated mice harbored lower ileal pathogen numbers and exhibited a better clinical outcome when compared to placebo controls. Furthermore, cumin-EO treatment alleviated enteropathogen-induced apoptotic cell responses in colonic epithelia. Whereas, on day 6 post-infection, a dampened secretion of pro-inflammatory mediators, including nitric oxide and IFN-γ to basal levels, could be assessed in mesenteric lymph nodes of cumin-EO treated mice, systemic MCP-1 concentrations were elevated in placebo counterparts only. In conclusion, our preclinical intervention study provides first evidence for promising immune-modulatory effects of cumin-EO in the combat of human campylobacteriosis. Future studies should address antimicrobial and immune-modulatory effects of natural compounds as adjunct antibiotics-independent treatment option for infectious diseases.

Molecular Targets in Campylobacter Infections

“…Most important was the finding that the immunosuppressive drug rapamycin prevented campylobacteriosis in these mice and supported clearing of the pathogen [ 166 ], which provided the first experimental proof that the dampening of inflammation is a valuable target for prevention and treatment of C. jejuni infection. Furthermore, preclinical placebo-controlled intervention studies on SAB IL-10-deficient mice revealed that defined vitamins, including ascorbate [ 168 ] and vitamin D [ 73 , 169 ], the short chain fatty acid butyrate [ 170 ] and plant-derived compounds that have been used for an extensive period of time in traditional medicine, such as essential oils [ 171 , 172 , 173 , 174 ], curcumin [ 74 ], resveratrol [ 175 ], carvacrol [ 176 ], urolithin-A [ 177 ] and activated charcoal [ 178 ], effectively dampened inflammation in the course of murine campylobacteriosis. Their respective mechanisms of action demonstrate that (i) LOS activity, (ii) pro-inflammatory mediators including oxygen radicals, (iii) intestinal barrier function and (iv) C. jejuni -related pathogenicity factors are well suited as molecular targets for the treatment and prevention of campylobacteriosis [ 157 , 179 , 180 ].…”

Combination of organic acids benzoate, butyrate, caprylate, and sorbate provides a novel antibiotics-independent treatment option in the combat of acute campylobacteriosis

“…The depletion of the murine gut microbiota by antibiotic pretreatment facilitated establishment of the enteropathogens alongside the gastrointestinal tract, whereas the il-10 gene knockout rendered mice susceptible to bacterial LOS resulting in clinical signs and immune-pathological responses upon oral C. jejuni infection as seen in human campylobacteriosis ( Mousavi et al, 2020a ). This C. jejuni infection and inflammation model has already been validated on numerous compounds, such as vitamins ( Mousavi et al, 2020b ; Lobo de Sá et al, 2021a ), plant derived biomolecules ( Mousavi et al, 2020c , d ), essential oils ( Bereswill et al, 2021a ; Heimesaat et al, 2021 ; Mousavi et al, 2021 ), activated charcoal ( Bereswill et al, 2021b ) as well as the short chain fatty acid butyrate ( Du et al, 2022 ), in order to assess their anti-microbial and immunomodulatory properties in acute campylobacteriosis.…”

Disease alleviating effects following prophylactic lemon and coriander essential oil treatment in mice with acute campylobacteriosis

“…Our previous preclinical placebo-controlled intervention studies provided evidence for anti-pathogenic and immune-modulatory properties of several EOs derived from clove ( Bereswill et al, 2021 ), garlic ( Heimesaat et al, 2021b ), cardamom ( Heimesaat et al, 2021a ), and cumin ( Mousavi et al, 2021 ) in an acute murine campylobacteriosis model applying secondary abiotic (SAB) IL-10 deficient (IL-10 −/− ) mice. The secondary depletion of the commensal murine gut microbiota by antibiotic pretreatment and the lack of the anti-inflammatory il-10 gene are pivotal prerequisites for successful colonization of C. jejuni alongside the murine gastrointestinal tract and for the pathogen-induced pro-inflammatory immune responses mounting in acute enterocolitis ( Bereswill et al, 2011 ; Haag et al, 2012 ).…”