Skip to main content
Top
Published in: Digestive Diseases and Sciences 10/2017

01-10-2017 | Original Article

Mosapride Stabilizes Intestinal Microbiota to Reduce Bacterial Translocation and Endotoxemia in CCl4-Induced Cirrhotic Rats

Authors: Hong Xu, Jingfang Xiong, Jianjun Xu, Shuiming Li, Yang Zhou, Dongya Chen, Xinjun Cai, Jian Ping, Min Deng, Jianyong Chen

Published in: Digestive Diseases and Sciences | Issue 10/2017

Login to get access

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.
Literature
1.
go back to reference Caly WR, Strauss E. A prospective study of bacterial infections in patients with cirrhosis. J Hepatol. 1993;18:353–358.CrossRefPubMed Caly WR, Strauss E. A prospective study of bacterial infections in patients with cirrhosis. J Hepatol. 1993;18:353–358.CrossRefPubMed
2.
go back to reference Cirera I, Bauer TM, Navasa M, et al. Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol. 2001;34:32–37.CrossRefPubMed Cirera I, Bauer TM, Navasa M, et al. Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol. 2001;34:32–37.CrossRefPubMed
3.
4.
go back to reference Garcia-Tsao G, Wiest R. Gut microflora in the pathogenesis of the complications of cirrhosis. Best Pract Res Clin Gastroenterol. 2004;18:353–372.CrossRefPubMed Garcia-Tsao G, Wiest R. Gut microflora in the pathogenesis of the complications of cirrhosis. Best Pract Res Clin Gastroenterol. 2004;18:353–372.CrossRefPubMed
5.
go back to reference Bauer TM, Steinbrückner B, Brinkmann FE, et al. Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis. Am J Gastroenterol. 2001;96:2962–2967.CrossRefPubMed Bauer TM, Steinbrückner B, Brinkmann FE, et al. Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis. Am J Gastroenterol. 2001;96:2962–2967.CrossRefPubMed
6.
go back to reference Guarner C, Runyon BA, Heck M, Young S, Sheikh MY. Effect of long-term trimethoprim-sulfamethoxazole prophylaxis on ascites formation, bacterial translocation, spontaneous bacterial peritonitis, and survival in cirrhotic rats. Dig Dis Sci. 1999;44:1957–1962.CrossRefPubMed Guarner C, Runyon BA, Heck M, Young S, Sheikh MY. Effect of long-term trimethoprim-sulfamethoxazole prophylaxis on ascites formation, bacterial translocation, spontaneous bacterial peritonitis, and survival in cirrhotic rats. Dig Dis Sci. 1999;44:1957–1962.CrossRefPubMed
7.
go back to reference Chiva M, Guarner C, Peralta C, et al. Intestinal mucosal oxidative damage and bacterial translocation in cirrhotic rats. Eur J Gastroenterol Hepatol. 2003;15:145–150.CrossRefPubMed Chiva M, Guarner C, Peralta C, et al. Intestinal mucosal oxidative damage and bacterial translocation in cirrhotic rats. Eur J Gastroenterol Hepatol. 2003;15:145–150.CrossRefPubMed
8.
go back to reference Such J, Guardiola JV, de Juan J, et al. Ultrastructural characteristics of distal duodenum mucosa in patients with cirrhosis. Eur J Gastroenterol Hepatol. 2002;14:371–376.CrossRefPubMed Such J, Guardiola JV, de Juan J, et al. Ultrastructural characteristics of distal duodenum mucosa in patients with cirrhosis. Eur J Gastroenterol Hepatol. 2002;14:371–376.CrossRefPubMed
9.
go back to reference Paris L, Tonutti L, Vannini C, Bazzoni G. Structural organization of the tight junctions. Biochim Biophys Acta. 2008;1778:646–659.CrossRefPubMed Paris L, Tonutti L, Vannini C, Bazzoni G. Structural organization of the tight junctions. Biochim Biophys Acta. 2008;1778:646–659.CrossRefPubMed
10.
go back to reference Assimakopoulos SF, Tsamandas AC, Tsiaoussis GI, et al. Altered intestinal tight junctions’ expression in patients with liver cirrhosis: a pathogenetic mechanism of intestinal hyperpermeability. Eur J Clin Invest. 2012;42:439–446.CrossRefPubMed Assimakopoulos SF, Tsamandas AC, Tsiaoussis GI, et al. Altered intestinal tight junctions’ expression in patients with liver cirrhosis: a pathogenetic mechanism of intestinal hyperpermeability. Eur J Clin Invest. 2012;42:439–446.CrossRefPubMed
11.
go back to reference Chang CS, Chen GH, Lien HC, Yeh HZ. Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 1998;28:1187–1190.CrossRefPubMed Chang CS, Chen GH, Lien HC, Yeh HZ. Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 1998;28:1187–1190.CrossRefPubMed
12.
13.
go back to reference Okamura K, Sasaki N, Yamada M, Yamada H, Inokuma H. Effects of mosapride citrate, metoclopramide hydrochloride, lidocaine hydrochloride, and cisapride citrate on equine gastric emptying, small intestinal and caecal motility. Res Vet Sci. 2009;86:302–308.CrossRefPubMed Okamura K, Sasaki N, Yamada M, Yamada H, Inokuma H. Effects of mosapride citrate, metoclopramide hydrochloride, lidocaine hydrochloride, and cisapride citrate on equine gastric emptying, small intestinal and caecal motility. Res Vet Sci. 2009;86:302–308.CrossRefPubMed
14.
go back to reference Okubo H, Nakatsu Y, Sakoda H, et al. Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasmaglucagon-like peptide-1 level in a rodent model. Am J Physiol Gastrointest Liver Physiol. 2015;308:G151–G158.CrossRefPubMed Okubo H, Nakatsu Y, Sakoda H, et al. Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasmaglucagon-like peptide-1 level in a rodent model. Am J Physiol Gastrointest Liver Physiol. 2015;308:G151–G158.CrossRefPubMed
15.
go back to reference Fujisawa M, Murata T, Hori M, Ozaki H. The 5-HT4 receptor agonist mosapride attenuates NSAID-induced gastric mucosal damage. J Gastroenterol. 2010;45:179–186.CrossRefPubMed Fujisawa M, Murata T, Hori M, Ozaki H. The 5-HT4 receptor agonist mosapride attenuates NSAID-induced gastric mucosal damage. J Gastroenterol. 2010;45:179–186.CrossRefPubMed
16.
go back to reference Xu H, Zhou Y, Lu C, Ping J, Xu LM. Salvianolic acid B lowers portal pressure in cirrhotic rats and attenuates contraction of rat hepatic stellate cells by inhibiting RhoA signaling pathway. Lab Invest. 2012;92:1738–1748.CrossRefPubMed Xu H, Zhou Y, Lu C, Ping J, Xu LM. Salvianolic acid B lowers portal pressure in cirrhotic rats and attenuates contraction of rat hepatic stellate cells by inhibiting RhoA signaling pathway. Lab Invest. 2012;92:1738–1748.CrossRefPubMed
17.
go back to reference Giannone FA, Baldassarre M, Domenicali M, et al. Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl(4)-induced advanced cirrhosis. Lab Invest. 2012;92:384–395.CrossRefPubMed Giannone FA, Baldassarre M, Domenicali M, et al. Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl(4)-induced advanced cirrhosis. Lab Invest. 2012;92:384–395.CrossRefPubMed
18.
go back to reference Yang DH, Ye ZY, Xie YJ, He XJ, Xu WJ, Zhou WM. Effect of salvianolate on intestinal epithelium tight junction protein zonula occludens protein 1 in cirrhotic rats. World J Gastroenterol. 2012;18:7040–7047.CrossRefPubMedPubMedCentral Yang DH, Ye ZY, Xie YJ, He XJ, Xu WJ, Zhou WM. Effect of salvianolate on intestinal epithelium tight junction protein zonula occludens protein 1 in cirrhotic rats. World J Gastroenterol. 2012;18:7040–7047.CrossRefPubMedPubMedCentral
19.
go back to reference Francés R, Chiva M, Sánchez E, et al. Bacterial translocation is downregulated by anti-TNF-alpha monoclonal antibody administration in rats with cirrhosis and ascites. J Hepatol. 2007;46:797–803.CrossRefPubMed Francés R, Chiva M, Sánchez E, et al. Bacterial translocation is downregulated by anti-TNF-alpha monoclonal antibody administration in rats with cirrhosis and ascites. J Hepatol. 2007;46:797–803.CrossRefPubMed
20.
go back to reference Versalovic J, Koeuth T, Lupski JR. Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. Nucl Acids Res. 1991;19:6823–6831.CrossRefPubMedPubMedCentral Versalovic J, Koeuth T, Lupski JR. Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. Nucl Acids Res. 1991;19:6823–6831.CrossRefPubMedPubMedCentral
21.
go back to reference Wei G, Pan L, Du H, Chen J, Zhao L. ERIC-PCR fingerprinting-based community DNA hybridization to pinpoint genome-specific fragments asmolecular markers to identify and track populations common to healthy human guts. J Microbiol Methods. 2004;59:91–108.CrossRefPubMed Wei G, Pan L, Du H, Chen J, Zhao L. ERIC-PCR fingerprinting-based community DNA hybridization to pinpoint genome-specific fragments asmolecular markers to identify and track populations common to healthy human guts. J Microbiol Methods. 2004;59:91–108.CrossRefPubMed
22.
go back to reference Sidransky D, Tokino T, Hamilton SR, et al. Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors. Science. 1992;256:102–105.CrossRefPubMed Sidransky D, Tokino T, Hamilton SR, et al. Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors. Science. 1992;256:102–105.CrossRefPubMed
23.
go back to reference Scanlan PD, Shanahan F, O’Mahony C, Marchesi JR. Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn’s disease. J Clin Microbiol. 2006;44:3980–3988.CrossRefPubMedPubMedCentral Scanlan PD, Shanahan F, O’Mahony C, Marchesi JR. Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn’s disease. J Clin Microbiol. 2006;44:3980–3988.CrossRefPubMedPubMedCentral
24.
go back to reference Runyon BA, Borzio M, Young S, Squier SU, Guarner C, Runyon MA. Effect of selective bowel decontamination with norfloxacin on spontaneous bacterial peritonitis, translocation, and survival in an animal model of cirrhosis. Hepatology. 1995;21:1719–1724.PubMed Runyon BA, Borzio M, Young S, Squier SU, Guarner C, Runyon MA. Effect of selective bowel decontamination with norfloxacin on spontaneous bacterial peritonitis, translocation, and survival in an animal model of cirrhosis. Hepatology. 1995;21:1719–1724.PubMed
25.
go back to reference Ginés P, Rimola A, Planas R, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology. 1990;12:716–724.CrossRefPubMed Ginés P, Rimola A, Planas R, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology. 1990;12:716–724.CrossRefPubMed
26.
go back to reference Dupeyron C, Mangeney N, Sedrati L, Campillo B, Fouet P, Leluan G. Rapid emergence of quinolone resistance in cirrhotic patients treated with norfloxacin to prevent spontaneous bacterial peritonitis. Antimicrob Agents Chemother. 1994;38:340–344.CrossRefPubMedPubMedCentral Dupeyron C, Mangeney N, Sedrati L, Campillo B, Fouet P, Leluan G. Rapid emergence of quinolone resistance in cirrhotic patients treated with norfloxacin to prevent spontaneous bacterial peritonitis. Antimicrob Agents Chemother. 1994;38:340–344.CrossRefPubMedPubMedCentral
27.
go back to reference Ewaschuk J, Endersby R, Thiel D, et al. Probiotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis. Hepatology. 2007;46:841–850.CrossRefPubMed Ewaschuk J, Endersby R, Thiel D, et al. Probiotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis. Hepatology. 2007;46:841–850.CrossRefPubMed
28.
go back to reference Versalovic J. Probiotics: intestinal gatekeeping, immunomodulation, and hepatic injury. Hepatology. 2007;46:618–621.CrossRefPubMed Versalovic J. Probiotics: intestinal gatekeeping, immunomodulation, and hepatic injury. Hepatology. 2007;46:618–621.CrossRefPubMed
29.
go back to reference Pardo A, Bartolí R, Lorenzo-Zúñiga V, et al. Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis. Hepatology. 2000;31:858–863.CrossRefPubMed Pardo A, Bartolí R, Lorenzo-Zúñiga V, et al. Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis. Hepatology. 2000;31:858–863.CrossRefPubMed
30.
go back to reference Madrid AM, Hurtado C, Venegas M, Cumsille F, Defilippi C. Long-term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function. Am J Gastroenterol. 2001;96:1251–1255.CrossRefPubMed Madrid AM, Hurtado C, Venegas M, Cumsille F, Defilippi C. Long-term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function. Am J Gastroenterol. 2001;96:1251–1255.CrossRefPubMed
31.
go back to reference Zhang SC, Wang W, Ren WY, He BM, Zhou K, Zhu WN. Effect of cisapride on intestinal bacterial and endotoxin translocation in cirrhosis. World J Gastroenterol. 2003;9:534–538.CrossRefPubMedPubMedCentral Zhang SC, Wang W, Ren WY, He BM, Zhou K, Zhu WN. Effect of cisapride on intestinal bacterial and endotoxin translocation in cirrhosis. World J Gastroenterol. 2003;9:534–538.CrossRefPubMedPubMedCentral
32.
go back to reference Tack J, Camilleri M, Chang L, et al. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35:745–767.CrossRefPubMedPubMedCentral Tack J, Camilleri M, Chang L, et al. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35:745–767.CrossRefPubMedPubMedCentral
33.
go back to reference Sánchez E, Soriano G, Mirelis B, et al. Effect of long-term acid gastric inhibition on bacterial translocation in cirrhotic rats. Eur J Gastroenterol Hepatol. 2015;27:570–576.CrossRefPubMed Sánchez E, Soriano G, Mirelis B, et al. Effect of long-term acid gastric inhibition on bacterial translocation in cirrhotic rats. Eur J Gastroenterol Hepatol. 2015;27:570–576.CrossRefPubMed
34.
go back to reference Su Y, Pan H, Guo Z, Zhou W, Zhang B. Bacterial translocation and endotoxemia after pringle maneuver in cirrhotic rats. Dig Dis Sci. 2015;60:414–419.CrossRefPubMed Su Y, Pan H, Guo Z, Zhou W, Zhang B. Bacterial translocation and endotoxemia after pringle maneuver in cirrhotic rats. Dig Dis Sci. 2015;60:414–419.CrossRefPubMed
35.
go back to reference Liedtke C, Luedde T, Sauerbruch T, et al. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects. Fibrogenesis Tissue Repair. 2013;6:19.CrossRefPubMedPubMedCentral Liedtke C, Luedde T, Sauerbruch T, et al. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects. Fibrogenesis Tissue Repair. 2013;6:19.CrossRefPubMedPubMedCentral
Metadata
Title
Mosapride Stabilizes Intestinal Microbiota to Reduce Bacterial Translocation and Endotoxemia in CCl4-Induced Cirrhotic Rats
Authors
Hong Xu
Jingfang Xiong
Jianjun Xu
Shuiming Li
Yang Zhou
Dongya Chen
Xinjun Cai
Jian Ping
Min Deng
Jianyong Chen
Publication date
01-10-2017
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 10/2017
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-017-4704-x

Other articles of this Issue 10/2017

Digestive Diseases and Sciences 10/2017 Go to the issue