Hong Xu1, Jingfang Xiong2, Jianjun Xu1, Shuiming Li3, Yang Zhou4,5, Dongya Chen1, Xinjun Cai6, Jian Ping4,5, Min Deng7, Jianyong Chen8. 1. Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China. 2. Department of Geriatrics, Hangzhou Red Cross Hospital, Hangzhou, China. 3. Key Laboratory of Marine Bioresources and Ecology, College of Life Science, Shenzhen University, Shenzhen, China. 4. Liver Cirrhosis Section, Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. 5. Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 6. Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, China. 7. Department of Emergency, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China. dengmindoctor@aliyun.com. 8. Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China. chenjy@medmail.com.cn.
Abstract
BACKGROUND: Impaired intestinal motility may lead to the disruption of gut microbiota equilibrium, which in turn facilitates bacterial translocation (BT) and endotoxemia in cirrhosis. We evaluated the influence of mosapride, a prokinetic agent, on BT and DNA fingerprints of gut microbiota in cirrhotic rats. METHODS: A rat model of cirrhosis was set up via subcutaneous injection of carbon tetrachloride (CCl4). The portal pressure, liver and intestinal damage, plasma endotoxin, BT, and intestinal transit rate (ITR) of cirrhotic rats were determined. Fecal DNA fingerprints were obtained by ERIC-PCR. The expressions of tight junction proteins were evaluated by western blotting. RESULTS: Mosapride treatment to cirrhotic rats significantly reduced the plasma endotoxin level and incidence of BT, accompanied by increased ITR. Cirrhotic rats (including those treated with mosapride) suffered from BT exhibited significantly lower ITR than those who are free of BT. Pearson coefficient indicated a significant and negative correlation between the plasma endotoxin level and ITR. The genomic fingerprints of intestinal microbiota from the three groups fell into three distinctive clusters. In the mosapride-treated group, Shannon's index was remarkably increased compared to the model group. Significantly positive correlation was detected between Shannon's index and ITR. Mosapride did not improve hepatic and intestinal damages and ileal expressions of occludin and ZO-1. CONCLUSIONS: Mosapride significantly increases intestinal motility in cirrhotic rats, thus to recover the disordered intestinal microbiota, finally resulting in decreased plasma endotoxin and BT.
BACKGROUND: Impaired intestinal motility may lead to the disruption of gut microbiota equilibrium, which in turn facilitates bacterial translocation (BT) and endotoxemia in cirrhosis. We evaluated the influence of mosapride, a prokinetic agent, on BT and DNA fingerprints of gut microbiota in cirrhotic rats. METHODS: A rat model of cirrhosis was set up via subcutaneous injection of carbon tetrachloride (CCl4). The portal pressure, liver and intestinal damage, plasma endotoxin, BT, and intestinal transit rate (ITR) of cirrhotic rats were determined. Fecal DNA fingerprints were obtained by ERIC-PCR. The expressions of tight junction proteins were evaluated by western blotting. RESULTS:Mosapride treatment to cirrhotic rats significantly reduced the plasma endotoxin level and incidence of BT, accompanied by increased ITR. Cirrhotic rats (including those treated with mosapride) suffered from BT exhibited significantly lower ITR than those who are free of BT. Pearson coefficient indicated a significant and negative correlation between the plasma endotoxin level and ITR. The genomic fingerprints of intestinal microbiota from the three groups fell into three distinctive clusters. In the mosapride-treated group, Shannon's index was remarkably increased compared to the model group. Significantly positive correlation was detected between Shannon's index and ITR. Mosapride did not improve hepatic and intestinal damages and ileal expressions of occludin and ZO-1. CONCLUSIONS:Mosapride significantly increases intestinal motility in cirrhotic rats, thus to recover the disordered intestinal microbiota, finally resulting in decreased plasma endotoxin and BT.
Authors: I Cirera; T M Bauer; M Navasa; J Vila; L Grande; P Taurá; J Fuster; J C García-Valdecasas; A Lacy; M J Suárez; A Rimola; J Rodés Journal: J Hepatol Date: 2001-01 Impact factor: 25.083