Neriman Şengül1, Fatma Töre2, Sevil Işık3, Belma Aslım4, Gülberk Uçar5, Tülin Fırat6, Samiye Yabanoğlu Çiftçi5, Aysel Kükner7. 1. Department of General Surgery, Abant İzzet Baysal University Faculty of Medicine, Bolu, Turkey. 2. Department of Physiology, İstanbul Atlas University Faculty of Medicine, İstanbul, Turkey. 3. Department of General Surgery, Ordu University Faculty of Medicine, Ordu, Turkey. 4. Department of Biology, Gazi University Faculty of Science, Ankara, Turkey. 5. Department of Biochemistry, Hacettepe University Faculty of Pharmacy, Ankara, Turkey. 6. Department of Histology and Embryology, Abant İzzet Baysal University Faculty of Medicine, Bolu, Turkey. 7. Department of Histology and Embryology, Near East University Faculty of Medicine, Nicosia, Turkish Republic of Northern Cyprus.
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 receiv- ing probiotic Lactobacillus delbrueckii subsp. Bulgaricus B3 strain for 7 days, colitis group, and sham group receiving only sodium chlo- ride. 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.
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 receiv- ing probiotic Lactobacillus delbrueckii subsp. Bulgaricus B3 strain for 7 days, colitis group, and sham group receiving only sodium chlo- ride. 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.