Digestive Diseases and Sciences

, Volume 64, Issue 12, pp 3402–3412 | Cite as

Efficacy of Probiotics and Synbiotics in Patients with Nonalcoholic Fatty Liver Disease: A Meta-Analysis

  • Liang Liu
  • Ping LiEmail author
  • Yiqi Liu
  • Yilian Zhang


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.


Probiotics Synbiotics Nonalcoholic fatty liver disease Meta-analysis 


Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10620_2019_5699_MOESM1_ESM.tif (370 kb)
Supplementary Fig. 1. Risk of bias summary: review authors’ judgements about each risk of bias item for each included study (TIFF 369 kb)
10620_2019_5699_MOESM2_ESM.tif (326 kb)
Supplementary Fig. 2. Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies (TIFF 325 kb)


  1. 1.
    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.PubMedGoogle Scholar
  2. 2.
    Fazel Y, Koenig AB, Sayiner M, Goodman ZD, Younossi ZM. Epidemiology and natural history of nonalcoholic fatty liver disease. Metabolism. 2016;65:1017–1025.PubMedGoogle Scholar
  3. 3.
    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.PubMedGoogle Scholar
  4. 4.
    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.PubMedGoogle Scholar
  5. 5.
    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.PubMedPubMedCentralGoogle Scholar
  6. 6.
    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.Google Scholar
  7. 7.
    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.PubMedGoogle Scholar
  8. 8.
    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.Google Scholar
  9. 9.
    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.PubMedGoogle Scholar
  10. 10.
    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.PubMedPubMedCentralGoogle Scholar
  11. 11.
    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.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Chichester: Wiley Online Library; 2008.Google Scholar
  13. 13.
    Saverymuttu SHJA, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J. 1986;292:13–15.Google Scholar
  14. 14.
    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.PubMedGoogle Scholar
  15. 15.
    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.PubMedPubMedCentralGoogle Scholar
  16. 16.
    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.PubMedGoogle Scholar
  17. 17.
    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.PubMedPubMedCentralGoogle Scholar
  18. 18.
    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.Google Scholar
  19. 19.
    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.PubMedPubMedCentralGoogle Scholar
  20. 20.
    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.Google Scholar
  21. 21.
    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.PubMedGoogle Scholar
  22. 22.
    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.PubMedGoogle Scholar
  23. 23.
    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.PubMedGoogle Scholar
  24. 24.
    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.PubMedGoogle Scholar
  25. 25.
    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.PubMedGoogle Scholar
  26. 26.
    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.Google Scholar
  27. 27.
    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.PubMedGoogle Scholar
  28. 28.
    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.PubMedGoogle Scholar
  29. 29.
    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.PubMedGoogle Scholar
  30. 30.
    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.PubMedGoogle Scholar
  31. 31.
    Leung C, Rivera L, Furness JB, et al. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol. 2016;13:412–425.PubMedGoogle Scholar
  32. 32.
    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.PubMedGoogle Scholar
  33. 33.
    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.Google Scholar
  34. 34.
    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.PubMedGoogle Scholar
  35. 35.
    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.PubMedPubMedCentralGoogle Scholar
  36. 36.
    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.PubMedGoogle Scholar
  37. 37.
    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.PubMedGoogle Scholar
  38. 38.
    Patrice DC, Nathalie MD. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des. 2009;15:1546–1558.Google Scholar
  39. 39.
    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.PubMedGoogle Scholar
  40. 40.
    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.PubMedGoogle Scholar
  41. 41.
    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.PubMedPubMedCentralGoogle Scholar
  42. 42.
    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.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of GraduateTianjin Medical UniversityTianjinChina
  2. 2.Department of HepatologyTianjin Second People’s HospitalTianjinChina
  3. 3.Tianjin Research Institute of Liver DiseasesTianjinChina

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