Human Defensin-5 Blocks Ethanol and Colitis-Induced Dysbiosis, Tight Junction Disruption and Inflammation in Mouse Intestine

• Published in: Scientific reports 2018-11, Vol.8 (1), p.16241-14, Article 16241
• Main Authors: Shukla, Pradeep K., Meena, Avtar S., Rao, Vaishnavi, Rao, Roshan G., Balazs, Louisa, Rao, RadhaKrishna
• Format: Article
• Language: English
• Subjects: 14; 14/19; 38; 38/77; 692/308/1426; 692/4020/1503/1581; 82; 82/83; Alcohol; Chemokines; Colitis; Colon; Cytokines; Defensins; Dextran; Dextran sulfate; Dysbacteriosis; E coli; Endotoxemia; Ethanol; Firmicutes; Humanities and Social Sciences; Inflammation; Inflammatory bowel disease; Mucosa; multidisciplinary; Probiotics; Remission; Science; Science (multidisciplinary); Small intestine; Sodium
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-34263-4

Alcohol consumption has been shown to cause dysbiosis, but the mechanism involved in it is unknown. Recurrent colitis is known to induce expression of α-defensins in the colon, but the effect of alcohol consumption on it is not known. We investigated the effect of ethanol on α-defensin expression in the small intestine and colitis-induced expression in colon in mice. Furthermore, we evaluated the effect of human defensin-5 (HD5) on ethanol and colitis-induced gut barrier dysfunction and mucosal damage. Recurrent colitis was induced by feeding dextran sulfate sodium (DSS), 3 cycles of 5-days each with 15 days intervals, followed by 30-days remission. Ethanol was fed during the intervals and recovery in a liquid diet with or without HD5. Expression of α-defensins, tight junction (TJ) integrity and cytokine/chemokine expression were analyzed. Chronic ethanol feeding reduced α-defensin expression in the small intestine and colitis-induced defensin expression in the colon. HD5 attenuated the growth of enterotoxigenic Bacteriodes fragilis and E. coli , but had no effect on non-toxigenic Bacteriodes fragilis or probiotics, the Lactobacilli . Ethanol and colitis elevated Enterobacteriaceae , Firmicutes and Firmicutes to Bacteriodetes ratio in colonic mucosa. HD5 feeding attenuated ethanol and colitis-induced dysbiosis, disruption of intestinal epithelial TJ, mucosal inflammation, expression of pro-inflammatory cytokines and chemokines in the small intestine and colon, and endotoxemia. These results demonstrate that ethanol suppresses intestinal α-defensin expression, leading to dysbiosis, barrier dysfunction, inflammation and endotoxemia. HD5 feeding attenuates intestinal injury caused by ethanol and colitis, indicating that defensin expression is a potential target for treatment of alcoholic tissue injury and colitis.