The paper provides a basic review of intestinal microflora and its importance in liver diseases. The intestinal microflora has many important functions, above all to maintain the microbial barrier against established as well as potential pathogens. Furthermore, it influences the motility and perfusion of the intestinal wall, stimulates the intestinal immune system and therefore also the so-called common mucosal immune system, reducing bacterial translocation and producing vitamins. Immune homeostasis at mucosal level results from a controlled response to intestinal luminal antigens. In liver cirrhosis, there are many changes in its function, mostly an increase in bacterial overgrowth and translocation. In this review, probiotics and their indications in hepatology are generally discussed. According to recent knowledge, these preparations are indicated in clinical practice only for cases of hepatic encephalopathy. Probiotics are able to decrease the permeability of the intestinal wall, and decrease bacterial translocation and endotoxemia in animal models as well as in clinical studies, which is extremely important in the prevention of complications of liver cirrhosis and infection after liver transplantation. Probiotics could limit oxidative and inflammatory liver damage and, in some situations, improve the histological state, and thus non-alcoholic steatohepatitis could be considered as another possible indication.

Department of Internal Medicine Faculty of Medicine and University Hospital Ostrava University 708 52 Ostrava Poruba Czech Republic

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Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371:651–659. PubMed

Gratz SW, Mykkanen H, El-Nezami HS. Probiotics and gut health: a special focus on liver diseases. World J Gastroenterol. 2010;16:403–410. PubMed PMC

Yoshioka H, Iseki K, Fujita K. Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants. Pediatrics. 1983;72:317–321. PubMed

Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001;291:881–884. PubMed

Mackie RI, Sghir A, Gaskins HR. Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr. 1999;69:1035S–1045S. PubMed

Saavedra JM, Tschernia A. Human studies with probiotics and prebiotics: clinical implications. Br J Nutr. 2002;87 Suppl 2:S241–S246. PubMed

Macpherson AJ, Harris NL. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol. 2004;4:478–485. PubMed

Hanson LA, Yolken RH. In: Probiotics, other nutritional factors and intestinal microflora. Philadelphia: Lippincot-Raven; 1999. pp. 18–67.

Koulaouzidis A, Bhat S, Saeed AA. Spontaneous bacterial peritonitis. World J Gastroenterol. 2009;15:1042–1049. PubMed PMC

Lata J, Stiburek O, Kopacova M. Spontaneous bacterial peritonitis: a severe complication of liver cirrhosis. World J Gastroenterol. 2009;15:5505–5510. PubMed PMC

Ersöz G, Aydin A, Erdem S, Yüksel D, Akarca U, Kumanlioglu K. Intestinal permeability in liver cirrhosis. Eur J Gastroenterol Hepatol. 1999;11:409–412. PubMed

Goulis J, Patch D, Burroughs AK. Bacterial infection in the pathogenesis of variceal bleeding. Lancet. 1999;353:139–142. PubMed

Berg RD, Garlington AW. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infect Immun. 1979;23:403–411. PubMed PMC

Guarner C, Runyon BA, Young S, Heck M, Sheikh MY. Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites. J Hepatol. 1997;26:1372–1378. PubMed

Ramachandran A, Balasubramanian KA. Intestinal dysfunction in liver cirrhosis: Its role in spontaneous bacterial peritonitis. J Gastroenterol Hepatol. 2001;16:607–612. PubMed

Luyer MD, Buurman WA, Hadfoune M, Speelmans G, Knol J, Jacobs JA, Dejong CH, Vriesema AJ, Greve JW. Strain-specific effects of probiotics on gut barrier integrity following hemorrhagic shock. Infect Immun. 2005;73:3686–3692. PubMed PMC

Rachmilewitz D, Katakura K, Karmeli F, Hayashi T, Reinus C, Rudensky B, Akira S, Takeda K, Lee J, Takabayashi K, et al. Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology. 2004;126:520–528. PubMed

Guarner C, Soriano G. Bacterial translocation and its consequences in patients with cirrhosis. Eur J Gastroenterol Hepatol. 2005;17:27–31. PubMed

Metchnikoff E. Prolongation of life- Optimistic Studies. New York: Putnam and Sons; 1908.

Havenaar R, Ten Brink B, Huis in't Veld JHJ. Selection of strains for probiotic use. Probiotics: the Scientific Basis) London: Chapman and Hall; 1992. pp. 209–224.

Gupta A, Dhiman RK, Kumari S, Rana S, Agarwal R, Duseja A, Chawla Y. Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol. 2010;53:849–855. PubMed

http://www. worldgastroenterology.org/guidelines/19_probiotics_prebiotics.

Foster KJ, Lin S, Turck CJ. Current and emerging strategies for treating hepatic encephalopathy. Crit Care Nurs Clin North Am. 2010;22:341–350. PubMed

Macbeth WA, Kass EH, Mcdermott WV Jr. Treatment of hepatic encephalopathy by alteration of intestinal flora with lactobacillus acidophilus. Lancet. 1965;1:399–403. PubMed

Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology. 2004;39:1441–1449. PubMed

Boca M, Vyskocil M, Mikulecký M, Ebringer L, Kolibás E, Kratochvíl'ová H, Buzgová D. [Complex therapy of chronic hepatic encephalopathy supplemented with probiotic: comparison of two studies] Cas Lek Cesk. 2004;143:324–328. PubMed

Loguercio C, Del Vecchio Blanco C, Coltorti M. Enterococcus lactic acid bacteria strain SF68 and lactulose in hepatic encephalopathy: a controlled study. J Int Med Res. 1987;15:335–343. PubMed

Solga SF. Probiotics can treat hepatic encephalopathy. Med Hypotheses. 2003;61:307–313. PubMed

Malaguarnera M, Gargante MP, Malaguarnera G, Salmeri M, Mastrojeni S, Rampello L, Pennisi G, Li Volti G, Galvano F. Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2010;22:199–206. PubMed

Bajaj JS, Saeian K, Christensen KM, Hafeezullah M, Varma RR, Franco J, Pleuss JA, Krakower G, Hoffmann RG, Binion DG. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol. 2008;103:1707–1715. PubMed

Jia L, Zhang MH. Comparison of probiotics and lactulose in the treatment of minimal hepatic encephalopathy in rats. World J Gastroenterol. 2005;11:908–911. PubMed PMC

Llovet JM, Bartolí R, March F, Planas R, Viñado B, Cabré E, Arnal J, Coll P, Ausina V, Gassull MA. Translocated intestinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence. J Hepatol. 1998;28:307–313. PubMed

Bauer TM, Fernández J, Navasa M, Vila J, Rodés J. Failure of Lactobacillus spp. to prevent bacterial translocation in a rat model of experimental cirrhosis. J Hepatol. 2002;36:501–506. PubMed

Mangell P, Nejdfors P, Wang M, Ahrné S, Weström B, Thorlacius H, Jeppsson B. Lactobacillus plantarum 299v inhibits Escherichia coli-induced intestinal permeability. Dig Dis Sci. 2002;47:511–516. PubMed

Chiva M, Soriano G, Rochat I, Peralta C, Rochat F, Llovet T, Mirelis B, Schiffrin EJ, Guarner C, Balanzó J. Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis. J Hepatol. 2002;37:456–462. PubMed

Lata J, Novotný I, Príbramská V, Juránková J, Fric P, Kroupa R, Stibůrek O. The effect of probiotics on gut flora, level of endotoxin and Child-Pugh score in cirrhotic patients: results of a double-blind randomized study. Eur J Gastroenterol Hepatol. 2007;19:1111–1113. PubMed

Wu CD, Li MZ, Chen CL. Endotoxin-induced liver injury and plasma tumor necrosis factor alfa, interleukin 6 level changes in rabbits. Chin J Dig. 1995;15:256–258. PubMed

Loguercio C, Federico A, Tuccillo C, Terracciano F, D'Auria MV, De Simone C, Del Vecchio Blanco C. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol. 2005;39:540–543. PubMed

Chen L, Pan DD, Zhou J, Jiang YZ. Protective effect of selenium-enriched Lactobacillus on CCl4-induced liver injury in mice and its possible mechanisms. World J Gastroenterol. 2005;11:5795–5800. PubMed PMC

Tandon P, Moncrief K, Madsen K, Arrieta MC, Owen RJ, Bain VG, Wong WW, Ma MM. Effects of probiotic therapy on portal pressure in patients with cirrhosis: a pilot study. Liver Int. 2009;29:1110–1115. PubMed

Kirpich IA, Solovieva NV, Leikhter SN, Shidakova NA, Lebedeva OV, Sidorov PI, Bazhukova TA, Soloviev AG, Barve SS, McClain CJ, et al. Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol. 2008;42:675–682. PubMed PMC

Forsyth CB, Farhadi A, Jakate SM, Tang Y, Shaikh M, Keshavarzian A. Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis. Alcohol. 2009;43:163–172. PubMed PMC

Mutlu E, Keshavarzian A, Engen P, Forsyth CB, Sikaroodi M, Gillevet P. Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol Clin Exp Res. 2009;33:1836–1846. PubMed PMC

Marotta F, Barreto R, Wu CC, Naito Y, Gelosa F, Lorenzetti A, Yoshioka M, Fesce E. Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect. Chin J Dig Dis. 2005;6:193–197. PubMed

Stadlbauer V, Mookerjee RP, Hodges S, Wright GA, Davies NA, Jalan R. Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis. J Hepatol. 2008;48:945–951. PubMed

Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434–438. PubMed

Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003;37:1202–1219. PubMed

Medina J, Fernández-Salazar LI, García-Buey L, Moreno-Otero R. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. Diabetes Care. 2004;27:2057–2066. PubMed

Fedorak RN, Madsen KL. Probiotics and prebiotics in gastrointestinal disorders. Curr Opin Gastroenterol. 2004;20:146–155. PubMed

Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, Desimone C, Song XY, Diehl AM. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003;37:343–350. PubMed

Esposito E, Iacono A, Bianco G, Autore G, Cuzzocrea S, Vajro P, Canani RB, Calignano A, Raso GM, Meli R. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr. 2009;139:905–911. PubMed

Li Z, Soloski MJ, Diehl AM. Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease. Hepatology. 2005;42:880–885. PubMed

Ma X, Hua J, Li Z. Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J Hepatol. 2008;49:821–830. PubMed PMC

Velayudham A, Dolganiuc A, Ellis M, Petrasek J, Kodys K, Mandrekar P, Szabo G. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology. 2009;49:989–997. PubMed PMC

Lirussi F, Mastropasqua E, Orando S, Orlando R. Probiotics for non-alcoholic fatty liver disease and/or steatohepatitis. Cochrane Database Syst Rev. 2007:CD005165. PubMed PMC

Kanazawa H, Nagino M, Kamiya S, Komatsu S, Mayumi T, Takagi K, Asahara T, Nomoto K, Tanaka R, Nimura Y. Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy. Langenbecks Arch Surg. 2005;390:104–113. PubMed

Sugawara G, Nagino M, Nishio H, Ebata T, Takagi K, Asahara T, Nomoto K, Nimura Y. Perioperative synbiotic treatment to prevent postoperative infectious complications in biliary cancer surgery: a randomized controlled trial. Ann Surg. 2006;244:706–714. PubMed PMC

Reddy BS, Macfie J, Gatt M, Larsen CN, Jensen SS, Leser TD. Randomized clinical trial of effect of synbiotics, neomycin and mechanical bowel preparation on intestinal barrier function in patients undergoing colectomy. Br J Surg. 2007;94:546–554. PubMed

Rayes N, Hansen S, Seehofer D, Müller AR, Serke S, Bengmark S, Neuhaus P. Early enteral supply of fiber and Lactobacilli versus conventional nutrition: a controlled trial in patients with major abdominal surgery. Nutrition. 2002;18:609–615. PubMed

Rayes N, Seehofer D, Theruvath T, Schiller RA, Langrehr JM, Jonas S, Bengmark S, Neuhaus P. Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation--a randomized, double-blind trial. Am J Transplant. 2005;5:125–130. PubMed

Jurankova J, Příbramska V, Lata J, Sauer P, Stosova T, Studenik P, Mejzlik V, Skacelova H, Koukalova D. Demonstration of bacterial translocation after liver transplantation - first results. Ces a Slov Gastroent a Hepatol. 2008;62:253–258.