Effects of Probiotic Bacteria on Central Neuronal Activation in Experimental Colitis

Abstract

Background: Brain-gut axis dysregulation is observed in inflammatory bowel disease. However, the effect of altered gut flora on neuro-immunomodulation and its role in the pathogenesis of inflammatory bowel disease are unknown. The aims of this study are to determine (i) whether colitis modifies the expression of c-fos, a marker of general neuronal activation in the brain and (ii) whether this activation could be modulated by probiotic bacteria. Methods: In this study, 28 Sprague-Dawley rats were divided into 4 groups: colitis-probiotic group, non-colitis-fed-control group receiving probiotic Lactobacillus delbrueckii subsp. Bulgaricus B3 strain for 7 days, colitis group, and sham group receiving only sodium chloride. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid-ethanol. The expression of c-fos was detected by immunohistochemistry in the brain tissue. Cytokines and inflammatory mediators were analyzed in the plasma. Histological scores and oxidative status were analyzed in the colon samples. Results: The inflammatory response was accompanied by increased levels of cytokines, lipid peroxidation activities, c-fos expression in the medial nucleus of the amygdala, and decreased levels of antioxidant enzymes in the colitis (P < .001). Probiotic treatment reversed those effects. Also, histopathologic scores were significantly lower in the probiotic-treated groups compared to the colitis group (P = .035). In contrast, the expression of c-fos was significantly increased in the paraventricular nucleus of hypothalamus in the probiotic-treated rats (P <.001). Conclusion: Colitis and intestinal inflammation are associated with the activation of neurons in the limbic system creating stress-like effects in the brain. Probiotics diversely modulate limbic response and hypothalamic axis activity in addition to protective effects in inflammation.