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

Abstract

IntroductionThe food-borne Gram-negative bacterial pathogen Campylobacter jejuni may cause the acute enterocolitis syndrome campylobacteriosis in infected humans. Given that human C. jejuni infections are rising globally which hold also true for resistance rates against antibiotic compounds such as macrolides and fluoroquinolones frequently prescribed for the treatment of severe infectious enteritis, novel antibiotics-independent therapeutic strategies are needed. Distinct organic acids are well known for their health-beneficial including anti-microbial and immunomodulatory properties. In our present study, we investigated potential pathogen-lowering and anti-inflammatory effects of benzoic acid, butyric acid, caprylic acid, and sorbic acid either alone or in combination during acute murine campylobacteriosis.MethodsTherefore, secondary abiotic IL-10–/– mice were perorally infected with C. jejuni strain 81–176 and subjected to a 4-day-course of respective organic acid treatment.Results and discussionOn day 6 post-infection, mice from the combination cohort displayed slightly lower pathogen loads in the duodenum, but neither in the stomach, ileum nor large intestine. Remarkably, the clinical outcome of C. jejuni induced acute enterocolitis was significantly improved after combined organic acid treatment when compared to the placebo control group. In support, the combinatory organic acid treatment dampened both, macroscopic and microscopic inflammatory sequelae of C. jejuni infection as indicated by less colonic shrinkage and less pronounced histopathological including apoptotic epithelial cell changes in the colon on day 6 post-infection. Furthermore, mice from the combination as compared to placebo cohort exhibited lower numbers of innate and adaptive immune cells such as neutrophilic granulocytes, macrophages, monocytes, and T lymphocytes in their colonic mucosa and lamina propria, respectively, which also held true for pro-inflammatory cytokine secretion in the large intestines and mesenteric lymph nodes. Notably, the anti-inflammatory effects were not restricted to the intestinal tract, but could also be observed systemically given pro-inflammatory mediator concentrations in C. jejuni infected mice from the combination organic acid treatment that were comparable to basal values. In conclusion, our in vivo study provides first evidence that an oral application of distinct organic acids in combination exhibits pronounced anti-inflammatory effects and hence, constitutes a promising novel antibiotics-independent therapeutic strategy in the combat of acute campylobacteriosis.

Origin and Function of Monocytes in Inflammatory Bowel Disease

“…112 They also significantly express α4β7 integrins, promoting wound healing at the lesion sites. 62,113 Notably, in UC patients with anxiety and depression symptoms, the percentage of intermediate and non-classical monocytes in peripheral blood is higher, their phagocytic function is reduced, and these cells' functions are impaired. 114 This indicates that the phenotype of monocytes subgroups can vary with or without coexisting diseases.…”

Therapeutic effects of oral benzoic acid application during acute murine campylobacteriosis

“…the animals develop an acute enteritis syndrome, accompanied by pronounced intestinal, extraintestinal, and systemic pro-inflammatory responses [16,[30][31][32]. This C. jejuni infection and inflammation model has already been used successfully for testing the efficacy of various molecules and compounds in preclinical studies to evaluate their anti-bacterial, as well as anti-inflammatory properties and ultimately therapeutic potential during murine campylobacteriosis [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50].…”

“…Previously, we have investigated benzoic acid in combination with different organic acids, including butyric acid, caprylic acid, and sorbic acid, for disease-alleviating properties during murine C. jejuni induced enterocolitis. The organic acid combination exhibited pronounced anti-inflammatory effects and ultimately reduced symptoms of C. jejuni induced disease [49]. Therefore, it was of high interest to investigate benzoic acid as a novel therapeutic strategy, now applied individually, in the combat of acute campylobacteriosis.…”

Not only for Christmas: Prophylactic oral application of trans-cinnamaldehyde alleviates acute murine campylobacteriosis

“…[ 27 , 28 ]. Our previous studies addressing the disease-alleviating effects of urolithin-A [ 31 ], of activated charcoal [ 32 ], of the iron-chelating compound deferoxamine [ 33 ], of essential oils derived from garlic [ 34 ], cardamom [ 35 ], cumin [ 36 ], clove [ 37 ], coriander, and lemon [ 38 ], of phenolic compounds such as carvacrol [ 39 ], resveratrol [ 40 ], and curcumin [ 41 ], of organic acids including butyrate, benzoate, caprylate, and sorbate [ 42 , 43 ], and furthermore, of the vitamins ascorbate [ 44 ] and vitamin D [ 45 ] have underlined the suitability of the here applied secondary abiotic IL-10 −/− mice as preclinical setting to test antibiotics-independent therapeutic and preventive measures in the combat of campylobacteriosis. In the present placebo-controlled intervention trail we therefore surveyed the disease-alleviating effects of prophylactic oral tran s-cinnamaldehyde application in secondary abiotic IL-10 −/− mice starting a week prior oral C. jejuni infection.…”