2013, Number 2
<< Back Next >>
Ann Hepatol 2013; 12 (2)
Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study
Wai-Sun WV, Lai-Hung WG, Mei-Ling CA, Chiu-Wing CW, Ka-Wai YD, Chi-To LK, Lik-Yuen CH
Language: English
References: 33
Page: 256-262
PDF size: 115.93 Kb.
ABSTRACT
Background. Probiotics have profound effect on nonalcoholic steatohepatitis (NASH) in animal models. We aimed to test the hypothesis that probiotics treatment was superior to usual care in reducing liver fat in NASH patients.
Material and methods. Patients with histology-proven NASH were randomized to receive probiotics (n = 10) or usual care (n = 10) for 6 months. The Lepicol probiotic formula contained
Lactobacillus plantarum, Lactobacillus deslbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus and
Bifidobacterium bifidum. The primary endpoint was change in intrahepatic triglyceride content (IHTG), as measured by proton-magnetic resonance spectroscopy, from baseline to month 6. Secondary endpoints included changes in liver biochemistry and metabolic profile.
Results. IHTG decreased from 22.6 ± 8.2% to 14.9 ± 7.0% in the probiotic group (P = 0.034) but remained static in the usual care group (16.9 ± 6.1% to 16.0 ± 6.6%; P = 0.55). Six subjects in the probiotic group had IHTG reduced by more than 30% from baseline, compared to 2 subjects in the usual care group (P = 0.17). The probiotic group also had greater reduction in serum aspartate aminotransferase level (P = 0.008). On the other hand, the use of probiotics was not associated with changes in body mass index, waist circumference, glucose and lipid levels.
Conclusions. Probiotics treatment may reduce liver fat and AST level in NASH patients. The therapeutic potential of probiotics in NASH should be tested in larger studies.
REFERENCES
Wong VW, Chu WC, Wong GL, Chan RS, Chim AM, Ong A, Yeung DK, et al. Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut 2012; 61: 409-15.
Wong VW, Wong GL, Choi PC, Chan AW, Li MK, Chan HY, Chim AM, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 2010; 59: 969-74.
Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010; 51: 1972-8.
Bhala N, Angulo P, van der Poorten D, Lee E, Hui JM, Saracco G, Adams LA, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011; 54: 1208-16.
Wong VW, Chan HL. Prevention of hepatocellular carcinoma: a concise review of contemporary issues. Ann Hepatol 2012; 11: 284-93.
Rodriguez-Hernandez H, Cervantes-Huerta M, Rodriguez-Moran M, Guerrero-Romero F. Decrease of aminotransferase levels in obese women is related to body weight reduction, irrespective of type of diet. Ann Hepatol 2011; 10: 486-92.
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444: 1027-31.
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464: 59-65.
Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444: 1022-3.
Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, et al. A core gut microbiome in obese and lean twins. Nature 2009; 457: 480-4.
Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Masciana R, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 2009; 49: 1877-87.
Spencer MD, Hamp TJ, Reid RW, Fischer LM, Zeisel SH, Fodor AA. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology 2011; 140: 976-86.
Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, Desimone C, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 2003; 37: 343-50.
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: 821-30.
Esposito E, Iacono A, Bianco G, Autore G, Cuzzocrea S, Vajro P, Canani RB, et al. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr 2009; 139: 905-11.
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: 989-97.
Parnell JA, Raman M, Rioux KP, Reimer RA. The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance. Liver Int 2012; 32: 701-11.
Delzenne NM, Williams CM. Prebiotics and lipid metabolism. Curr Opin Lipidol 2002; 13: 61-7.
Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 2007; 50: 2374-83.
Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009; 58: 1091-103.
Forcheron F, Cachefo A, Thevenon S, Pinteur C, Beylot M. Mechanisms of the triglyceride- and cholesterol-lowering effect of fenofibrate in hyperlipidemic type 2 diabetic patients. Diabetes 2002; 51: 3486-91.
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-21.
Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, Choi PC, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 2010; 51: 454-62.
Abenavoli L, Beaugrand M. Transient elastography in nonalcoholic fatty liver disease. Ann Hepatol 2012; 11: 172-8.
Nardone G, Compare D, Liguori E, Di Mauro V, Rocco A, Barone M, Napoli A, et al. Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury. Am J Physiol Gastrointest Liver Physiol 2010; 299: G669-G676.
Rosberg-Cody E, Stanton C, O’Mahony L, Wall R, Shanahan F, Quigley EM, Fitzgerald GF, et al. Recombinant lactobacilli expressing linoleic acid isomerase can modulate the fatty acid composition of host adipose tissue in mice. Microbiology 2011; 157: 609-15.
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: 540-3.
Aller R, De Luis DA, Izaola O, Conde R, Gonzalez Sagrado M, Primo D, De La Fuente B, et al. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: a double blind randomized clinical trial. Eur Rev Med Pharmacol Sci 2011; 15: 1090-5.
McPherson S, Jonsson JR, Cowin GJ, O’Rourke P, Clouston AD, Volp A, Horsfall L, et al. Magnetic resonance imaging and spectroscopy accurately estimate the severity of steatosis provided the stage of fibrosis is considered. J Hepatol 2009; 51: 389-97.
Osman N, Adawi D, Molin G, Ahrne S, Berggren A, Jeppsson B. Bifidobacterium infantis strains with and without a combination of oligofructose and inulin (OFI) attenuate inflammation in DSS-induced colitis in rats. BMC Gastroenterol 2006; 6: 31.
Osman N, Adawi D, Ahrne S, Jeppsson B, Molin G. Probiotics and blueberry attenuate the severity of dextran sulfate sodium (DSS)-induced colitis. Dig Dis Sci 2008; 53: 2464-73.
Gabele E, Dostert K, Hofmann C, Wiest R, Scholmerich J, Hellerbrand C, Obermeier F. DSS induced colitis increases portal LPS levels and enhances hepatic inflammation and fibrogenesis in experimental NASH. J Hepatol 2011; 55: 1391-9.
Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, Thaiss CA, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012; 482: 179-85.