Background and Aim
Extensive epidemiological evidence suggests that nonalcoholic fatty liver disease (NAFLD) is the primary chronic liver disease worldwide. However, some studies have showed conflicting results on the effects of probiotics and synbiotics supplementation. Therefore, we conducted a systematic review and meta-analysis to investigate the effectiveness of the supplementation in subjects with NAFLD.
We searched systematically PubMed, Cochrane, and Embase databases up to April 2018 and checked manually the bibliography of the original articles. The quality of the studies was evaluated using the Cochrane Risk of Bias Tool.
This study analyzed 15 randomized, controlled trials involving 782 patients with NAFLD. Probiotics and synbiotics supplementation could significantly improve liver steatosis, alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, homeostasis model assessment-insulin resistance, liver stiffness and tumor necrosis factor-alpha (all P < 0.05). But the supplementation could not ameliorate body mass index (mean difference [MD] = −0.00; 95% confidence interval [CI]: −0.22 to 0.22, P = 0.99), waist circumference (MD = −0.01; 95% CI −0.03 to 0.02, P = 0.57) and fasting blood sugar (standard mean difference [SMD] = −0.10; 95% CI −0.32 to 0.12, P = 0.39).
We present clear evidence for the benefit of probiotics and synbiotics supplementation for liver steatosis, liver enzymes, lipid profiles and liver stiffness in patients with NAFLD.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol. 2005;42:132–138.
Fazel Y, Koenig AB, Sayiner M, Goodman ZD, Younossi ZM. Epidemiology and natural history of nonalcoholic fatty liver disease. Metabolism. 2016;65:1017–1025.
Miele L, Targher G. Understanding the association between developing a fatty liver and subsequent cardio-metabolic complications. Expert Rev Gastroenterol Hepatol. 2015;9:1243–1245.
Kasturiratne A, Weerasinghe S, Dassanayake AS, et al. Influence of nonalcoholic fatty liver disease on the development of diabetes mellitus. J Gastroenterol Hepatol. 2013;28:142–147.
Musso G, Gambino R, Tabibian JH, et al. Association of nonalcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med. 2014;11:e1001680.
Miraghajani M, Zaghian N, Dehkohneh A, Mirlohi M, Ghiasvand R. Probiotic soy milk consumption and renal function among type 2 diabetic patients with nephropathy: a randomized controlled clinical trial. Probiotics Antimicrob Proteins. 2017;1:1–9.
Khalesi S, Johnson DW, Campbell K, et al. Effect of probiotics and synbiotics consumption on serum concentrations of liver function test enzymes: a systematic review and meta-analysis. Eur J Nutr. 2017;57:2037–2053.
Lavekar AS, Raje DV, Manohar T, Lavekar AA. Role of probiotics in the treatment of nonalcoholic fatty liver disease: a meta-analysis. Euroasian J Hepatogastroenterol. 2017;7:130–137.
Gao X, Zhu Y, Wen Y, Liu G, Wan C. Efficacy of probiotics in nonalcoholic fatty liver disease in adult and children: a meta-analysis of randomized controlled trials. Hepatol Res. 2016;46:1226–1233.
Ma YY, Li L, Yu CH, Shen Z, Chen LH, Li YM. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol. 2013;19:6911–6918.
Moher D, Liberati A, Tetzlaff J, Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.
Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Chichester: Wiley Online Library; 2008.
Saverymuttu SHJA, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J. 1986;292:13–15.
Famouri F, Shariat Z, Hashemipour M, Keikha M, Kelishadi R. Effects of probiotics on nonalcoholic fatty liver disease in obese children and adolescents. J Pediatr Gastroenterol Nutr. 2017;64:413–417.
Asgharian A, Askari G, Esmailzade A, Feizi A, Mohammadi V. The effect of symbiotic supplementation on liver enzymes, c-reactive protein and ultrasound findings in patients with nonalcoholic fatty liver disease: a clinical trial. Int J Prev Med. 2016;7:59.
Nabavi S, Rafraf M, Somi MH, Homayouni-Rad A, Asghari-Jafarabadi M. Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease. J Dairy Sci. 2014;97:7386–7393.
Alisi A, Bedogni G, Baviera G, et al. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2014;39:1276–1285.
Javadi L, Ghavami M, Khoshbaten M, Safaiyan A, Barzegari A, Gargari BP. The effect of probiotic and/or prebiotic on liver function tests in patients with nonalcoholic fatty liver disease: a double blind randomized clinical trial. Iran Red Crescent Med J. 2017;4:131–138.
Behrouz V, Jazayeri S, Aryaeian N, Zahedi MJ, Hosseini F. Effects of probiotic and prebiotic supplementation on leptin, adiponectin, and glycemic parameters in nonalcoholic fatty liver disease: a randomized clinical trial. Middle East J Dig Dis. 2017;9:150–157.
Ekhlasi G, Mohammadi RK, Agah S, et al. Do symbiotic and vitamin e supplementation have favorite effects in nonalcoholic fatty liver disease? A randomized, double-blind, placebo-controlled trial. J Res Med Sci. 2016;21:98.
Wong VW, Won GL, Chim AM, et al. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann Hepatol. 2013;12:256–262.
Malaguarnera M, Vacante M, Antic T, et al. Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig Dis Sci. 2012;57:545–553.
Vajro P, Mandato C, Licenziati MR, et al. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr. 2011;52:740–743.
Aller R, De Luis DA, Izaola O, 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;15:1090–1095.
Manzhalii E, Virchenko O, Falalyeyeva T, Beregova T, Stremmel W. Treatment efficacy of a probiotic preparation for nonalcoholic steatohepatitis: a pilot trial. J Dig Dis. 2017;18:698–703.
Kobyliak N, Abenavoli L, Mykhalchyshyn G, et al. A multi-strain probiotic reduces the fatty liver index, cytokines and aminotransferase levels in NAFLD patients: evidence from a randomized clinical trial. J Gastrointest Liver Dis. 2018;27:41–49.
Mofidi F, Poustchi H, Yari Z, et al. Synbiotic supplementation in lean patients with nonalcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial. Br J Nutr. 2017;117:662–668.
Eslamparast T, Poustchi H, Zamani F, Sharafkhah M, Malekzadeh R, Hekmatdoost A. Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. Am J Clin Nutr. 2014;99:535–542.
Tarantino G, Finelli C. Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease. Future Microbiol. 2015;10:889–902.
Barengolts E. Gut microbiota, prebiotics, probiotics, and synbiotics in management of obesity and prediabetes: review of randomized controlled trials. Endocr Pract. 2016;22:1224–1234.
Leung C, Rivera L, Furness JB, et al. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol. 2016;13:412–425.
Cani PD, Neyrinck AM, Fava F, 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;50:2374–2383.
Wen JF, Ye GL, Zhang HX, Ding JX, Chen SH. Clinical efficacy of bifidobacterium triple active bacteria combined with polyene phosphatidylcholine on NASH. China Mod Dr. 2014;52:5–13.
Wang W, Shi LP, Shi L, Xu L. Efficacy of probiotics on the treatment of nonalcoholic fatty liver disease. Zhonghua Nei Ke Za Zhi. 2018;57:101–106.
Shavakhi A, Minakari M, Firouzian H, Assali R, Hekmatdoost A, Ferns G. Effect of a probiotic and metformin on liver aminotransferases in nonalcoholic steatohepatitis: a double blind randomized clinical trial. Int J Prev Med. 2013;4:531–537.
Zhang Y, Hu C, Hong J, et al. Lipid profiling reveals different therapeutic effects of metformin and glipizide in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2014;37:2804–2812.
Li Z, Yang S, Lin H, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003;37:343–350.
Patrice DC, Nathalie MD. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des. 2009;15:1546–1558.
Loguercio C, Federico A, Tuccillo C, et al. Beneficial effects of a probiotic VSL# 3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol. 2005;39:540–543.
Wagnerberger S, Spruss A, Kanuri G, et al. Lactobacillus casei Shirota protects from fructose-induced liver steatosis: a mouse model. J Nutr Biochem. 2013;24:531–538.
Velayudham A, Dolganiuc A, Ellis M, et al. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology. 2009;49:989–997.
Ting WJ, Kuo WW, Hsieh DJ, et al. Heat killed Lactobacillus reuteri GMNL-263 reduces fibrosis effects on the liver and heart in high fat diet-hamsters via TGF-β suppression. Int J Mol Sci. 2015;16:25881–25896.
Conflict of interest
The authors declare that they have no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
1. Risk of bias summary: review authors’ judgements about each risk of bias item for each included study (TIFF 369 kb)
2. Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies (TIFF 325 kb)
Rights and permissions
About this article
Cite this article
Liu, L., Li, P., Liu, Y. et al. Efficacy of Probiotics and Synbiotics in Patients with Nonalcoholic Fatty Liver Disease: A Meta-Analysis. Dig Dis Sci 64, 3402–3412 (2019). https://doi.org/10.1007/s10620-019-05699-z
- Nonalcoholic fatty liver disease