Hepatitis Monthly

Published by: Kowsar

Probiotics as a Novel Treatment for Non-Alcoholic Fatty Liver Disease; A Systematic Review on the Current Evidences

Roya Kelishadi 1 , Sanam Farajian 2 , * and Maryam Mirlohi 2
Authors Information
1 Faculty of Medicine and Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, IR Iran
2 Faculty of Nutrition and Food Sciences, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, IR Iran
Article information
  • Hepatitis Monthly: April 01, 2013, 13 (4); e7233
  • Published Online: April 9, 2013
  • Article Type: Review Article
  • Received: July 13, 2012
  • Revised: August 1, 2012
  • Accepted: August 22, 2012
  • DOI: 10.5812/hepatmon.7233

To Cite: Kelishadi R, Farajian S, Mirlohi M. Probiotics as a Novel Treatment for Non-Alcoholic Fatty Liver Disease; A Systematic Review on the Current Evidences, Hepat Mon. 2013 ; 13(4):e7233. doi: 10.5812/hepatmon.7233.

Copyright © 2013, Kowsar Corp. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Context
2. Evidence Acquisition
3. Results
4. Conclusion
  • 1. Kelishadi R, Poursafa P. Obesity and air pollution: global risk factors for pediatric non-alcoholic fatty liver disease. Hepat Mon. 2011; 11(10): 794-802[DOI][PubMed]
  • 2. Alavian SM, Mohammad-Alizadeh AH, Esna-Ashari F, Ardalan G, Hajarizadeh B. Non-alcoholic fatty liver disease prevalence among school-aged children and adolescents in Iran and its association with biochemical and anthropometric measures. Liver Int. 2009; 29(2): 159-63[DOI][PubMed]
  • 3. Esposito E, Iacono A, Bianco G, Autore G, Cuzzocrea S, Vajro P, et al. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr. 2009; 139(5): 905-11[DOI][PubMed]
  • 4. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004; 40(6): 1387-95[DOI][PubMed]
  • 5. Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Tani S, Goto M. Prevalence of fatty liver in a general population of Okinawa, Japan. Jpn J Med. 1988; 27(2): 142-9[PubMed]
  • 6. Bjornsson E, Angulo P. Non-alcoholic fatty liver disease. Scand J Gastroenterol. 2007; 42(9): 1023-30[DOI][PubMed]
  • 7. Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology. 2005; 42(1): 44-52[DOI][PubMed]
  • 8. Chitturi S, Wong VW, Farrell G. Nonalcoholic fatty liver in Asia: Firmly entrenched and rapidly gaining ground. J Gastroenterol Hepatol. 2011; 26: 163-72[DOI][PubMed]
  • 9. Browning JD. Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology. 2006; 44(2): 466-71[DOI][PubMed]
  • 10. Ruhl CE, Everhart JE. Epidemiology of nonalcoholic fatty liver. Clin Liver Dis. 2004; 8(3): 501-19[DOI][PubMed]
  • 11. Widhalm K, Ghods E. Nonalcoholic fatty liver disease: a challenge for pediatricians. Int J Obes (Lond). 2010; 34(10): 1451-67[DOI][PubMed]
  • 12. Caserta CA, Pendino GM, Amante A, Vacalebre C, Fiorillo MT, Surace P, et al. Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. Am J Epidemiol. 2010; 171(11): 1195-202[DOI][PubMed]
  • 13. Jamali R, Khonsari M, Merat S, Khoshnia M, Jafari E, Bahram Kalhori A, et al. Persistent alanine aminotransferase elevation among the general Iranian population: prevalence and causes. World J Gastroenterol. 2008; 14(18): 2867-71[PubMed]
  • 14. Kelishadi R, Cook SR, Adibi A, Faghihimani Z, Ghatrehsamani S, Beihaghi A, et al. Association of the components of the metabolic syndrome with non-alcoholic fatty liver disease among normal-weight, overweight and obese children and adolescents. Diabetol Metab Syndr. 2009; 1: 29[DOI][PubMed]
  • 15. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann Intern Med. 1997; 126(2): 137-45[PubMed]
  • 16. Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008; 28(4): 339-50[DOI][PubMed]
  • 17. Daniels SR. Regulation of body mass and management of childhood overweight. Pediatr Blood Cancer. 2005; 44(7): 589-94[DOI][PubMed]
  • 18. Lee S, Bacha F, Gungor N, Arslanian S. Comparison of different definitions of pediatric metabolic syndrome: relation to abdominal adiposity, insulin resistance, adiponectin, and inflammatory biomarkers. J Pediatr. 2008; 152(2): 177-84[DOI][PubMed]
  • 19. Szabo G, Bala S, Petrasek J, Gattu A. Gut-liver axis and sensing microbes. Dig Dis. 2010; 28(6): 737-44[DOI][PubMed]
  • 20. Day CP. Non-alcoholic steatohepatitis (NASH): where are we now and where are we going? Gut. 2002; 50(5): 585-8[PubMed]
  • 21. Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology. 1998; 114(4): 842-5[PubMed]
  • 22. Shanab AA, Scully P, Crosbie O, Buckley M, O'Mahony L, Shanahan F, et al. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8. Dig Dis Sci. 2011; 56(5): 1524-34[DOI][PubMed]
  • 23. Medina J, Fernandez-Salazar LI, Garcia-Buey L, Moreno-Otero R. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. Diabetes Care. 2004; 27(8): 2057-66[PubMed]
  • 24. Dunn W, Schwimmer JB. The obesity epidemic and nonalcoholic fatty liver disease in children. Curr Gastroenterol Rep. 2008; 10(1): 67-72[PubMed]
  • 25. Roberts EA. Pediatric nonalcoholic fatty liver disease (NAFLD): a "growing" problem? J Hepatol. 2007; 46(6): 1133-42[DOI][PubMed]
  • 26. Duvnjak M, Lerotic I, Barsic N, Tomasic V, Virovic Jukic L, Velagic V. Pathogenesis and management issues for non-alcoholic fatty liver disease. World J Gastroenterol. 2007; 13(34): 4539-50[PubMed]
  • 27. Kojima H, Sakurai S, Uemura M, Fukui H, Morimoto H, Tamagawa Y. Mitochondrial abnormality and oxidative stress in nonalcoholic steatohepatitis. Alcohol Clin Exp Res. 2007; 31(1 Suppl)-6[DOI][PubMed]
  • 28. Zheng MH, Xin YN, Li H, Cai XN, Cui YL, Qiu LX, et al. Probiotics: A possible specific liver drug for non-alcoholic fatty liver disease. Biosci Hypotheses. 2009; 2(1): 54-5
  • 29. Erickson SK. Nonalcoholic fatty liver disease. J Lipid Res. 2009; 50-6[DOI][PubMed]
  • 30. Nair S, Cope K, Risby TH, Diehl AM. Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis. Am J Gastroenterol. 2001; 96(4): 1200-4[DOI][PubMed]
  • 31. Solga SF, Diehl AM. Non-alcoholic fatty liver disease: lumen-liver interactions and possible role for probiotics. J Hepatol. 2003; 38(5): 681-7[PubMed]
  • 32. Lafyatis R, Farina A. New insights into the mechanisms of innate immune receptor signalling in fibrosis. Open Rheumatol J. 2012; 6: 72-9[DOI][PubMed]
  • 33. Liu X, Lazenby AJ, Clements RH, Jhala N, Abrams GA. Resolution of nonalcoholic steatohepatits after gastric bypass surgery. Obes Surg. 2007; 17(4): 486-92[DOI][PubMed]
  • 34. Iacono A, Raso GM, Canani RB, Calignano A, Meli R. Probiotics as an emerging therapeutic strategy to treat NAFLD: focus on molecular and biochemical mechanisms. J Nutr Biochem. 2011; 22(8): 699-711[DOI][PubMed]
  • 35. Jonkers D, Stockbrugger R. Review article: Probiotics in gastrointestinal and liver diseases. Aliment Pharmacol Ther. 2007; 26: 133-48[DOI][PubMed]
  • 36. Report of a Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria. 2001;
  • 37. Schattenberg JM, Galle PR. Animal models of non-alcoholic steatohepatitis: of mice and man. Dig Dis. 2010; 28(1): 247-54[DOI][PubMed]
  • 38. Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003; 37(2): 343-50[DOI][PubMed]
  • 39. Thurman RG, Bradford BU, Iimuro Y, Knecht KT, Connor HD, Adachi Y, et al. Role of Kupffer cells, endotoxin and free radicals in hepatotoxicity due to prolonged alcohol consumption: studies in female and male rats. J Nutr. 1997; 127(5 Suppl): 903S-6S[PubMed]
  • 40. Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A. 1997; 94(6): 2557-62[PubMed]
  • 41. Larter CZ, Farrell GC. Insulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat? J Hepatol. 2006; 44(2): 253-61[DOI][PubMed]
  • 42. Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med. 2000; 343(20): 1467-76[DOI][PubMed]
  • 43. 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(5): 821-30[DOI][PubMed]
  • 44. Gratz SW, Mykkanen H, El-Nezami HS. Probiotics and gut health: a special focus on liver diseases. World J Gastroenterol. 2010; 16(4): 403-10[PubMed]
  • 45. Meyer AL, Elmadfa I, Herbacek I, Micksche M. Probiotic, as well as conventional yogurt, can enhance the stimulated production of proinflammatory cytokines. J Hum Nutr Diet. 2007; 20(6): 590-8[DOI][PubMed]
  • 46. Velayudham A, Dolganiuc A, Ellis M, Petrasek J, Kodys K, Mandrekar P, et al. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology. 2009; 49(3): 989-97[DOI][PubMed]
  • 47. Rizki G, Arnaboldi L, Gabrielli B, Yan J, Lee GS, Ng RK, et al. Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1. J Lipid Res. 2006; 47(10): 2280-90[DOI][PubMed]
  • 48. Karahan N, Isler M, Koyu A, Karahan AG, Basyigit Kilic G, Ciris IM, et al. Effects of probiotics on methionine choline deficient diet-induced steatohepatitis in rats. Turk J Gastroenterol. 2012; 23(2): 110-21[PubMed]
  • 49. Lee HY, Park JH, Seok SH, Baek MW, Kim DJ, Lee KE, et al. Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta. 2006; 1761(7): 736-44[DOI][PubMed]
  • 50. Wang Y, Xu N, Xi A, Ahmed Z, Zhang B, Bai X. Effects of Lactobacillus plantarum MA2 isolated from Tibet kefir on lipid metabolism and intestinal microflora of rats fed on high-cholesterol diet. Appl Microbiol Biotechnol. 2009; 84(2): 341-7[DOI][PubMed]
  • 51. Fazeli H, Moshtaghian J, Mirlohi M, Shirzadi M. Reduction in serum lipid parameters by incorporation of a native strain of Lactobacillus Plantarum A7 in Mice. Iranian J Diabetes Lipid Dis. 2010; 9: 1-7
  • 52. Yadav H, Jain S, Sinha PR. Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats. Nutrition. 2007; 23(1): 62-8[DOI][PubMed]
  • 53. Paik HD, Park JS, Park E. Effects of Bacillus polyfermenticus SCD on lipid and antioxidant metabolisms in rats fed a high-fat and high-cholesterol diet. Biol Pharm Bull. 2005; 28(7): 1270-4[PubMed]
  • 54. Loguercio C, Federico A, Tuccillo C, Terracciano F, D'Auria MV, De Simone C, et al. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol. 2005; 39(6): 540-3[PubMed]
  • 55. Loguercio C, De Simone T, Federico A, Terracciano F, Tuccillo C, Di Chicco M, et al. Gut-liver axis: a new point of attack to treat chronic liver damage? Am J Gastroenterol. 2002; 97(8): 2144-6[DOI][PubMed]
  • 56. Aller R, De Luis DA, Izaola O, Conde R, Gonzalez Sagrado M, Primo D, 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(9): 1090-5[PubMed]
  • 57. Solga SF, Buckley G, Clark JM, Horska A, Diehl AM. The effect of a probiotic on hepatic steatosis. J Clin Gastroenterol. 2008; 42(10): 1117-9[DOI][PubMed]
  • 58. Carr FJ, Chill D, Maida N. The lactic acid bacteria: a literature survey. Crit Rev Microbiol. 2002; 28(4): 281-370[DOI][PubMed]
  • 59. Candela M, Seibold G, Vitali B, Lachenmaier S, Eikmanns BJ, Brigidi P. Real-time PCR quantification of bacterial adhesion to Caco-2 cells: competition between bifidobacteria and enteropathogens. Res Microbiol. 2005; 156(8): 887-95[DOI][PubMed]
  • 60. Collado MC, Meriluoto J, Salminen S. Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus. Lett Appl Microbiol. 2007; 45(4): 454-60[DOI][PubMed]
  • 61. Mukai T, Kaneko S, Matsumoto M, Ohori H. Binding of Bifidobacterium bifidum and Lactobacillus reuteri to the carbohydrate moieties of intestinal glycolipids recognized by peanut agglutinin. Int J Food Microbiol. 2004; 90(3): 357-62[PubMed]
  • 62. Roselli M, Finamore A, Britti MS, Mengheri E. Probiotic bacteria Bifidobacterium animalis MB5 and Lactobacillus rhamnosus GG protect intestinal Caco-2 cells from the inflammation-associated response induced by enterotoxigenic Escherichia coli K88. Br J Nutr. 2006; 95(6): 1177-84[PubMed]
  • 63. Sherman PM, Johnson-Henry KC, Yeung HP, Ngo PS, Goulet J, Tompkins TA. Probiotics reduce enterohemorrhagic Escherichia coli O157:H7- and enteropathogenic E. coli O127:H6-induced changes in polarized T84 epithelial cell monolayers by reducing bacterial adhesion and cytoskeletal rearrangements. Infect Immun. 2005; 73(8): 5183-8[DOI][PubMed]
  • 64. Tallon R, Arias S, Bressollier P, Urdaci MC. Strain- and matrix-dependent adhesion of Lactobacillus plantarum is mediated by proteinaceous bacterial compounds. J Appl Microbiol. 2007; 102(2): 442-51[DOI][PubMed]
  • 65. Johnson-Henry KC, Donato KA, Shen-Tu G, Gordanpour M, Sherman PM. Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli O157:H7-induced changes in epithelial barrier function. Infect Immun. 2008; 76(4): 1340-8[DOI][PubMed]
  • 66. Zyrek AA, Cichon C, Helms S, Enders C, Sonnenborn U, Schmidt MA. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCzeta redistribution resulting in tight junction and epithelial barrier repair. Cell Microbiol. 2007; 9(3): 804-16[DOI][PubMed]
  • 67. Ceponis PJ, Botelho F, Richards CD, McKay DM. Interleukins 4 and 13 increase intestinal epithelial permeability by a phosphatidylinositol 3-kinase pathway. Lack of evidence for STAT 6 involvement. J Biol Chem. 2000; 275(37): 29132-7[DOI][PubMed]
  • 68. Karnik S, Kanekar A. Childhood obesity: a global public health crisis. Int J Prev Med. 2012; 3(1): 1-7[PubMed]
  • 69. Kelishadi R. Childhood overweight, obesity, and the metabolic syndrome in developing countries. Epidemiol Rev. 2007; 29: 62-76[DOI][PubMed]
  • 70. Otte JM, Podolsky DK. Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. Am J Physiol Gastrointest Liver Physiol. 2004; 286(4)-26[DOI][PubMed]
  • 71. An HM, Park SY, Lee do K, Kim JR, Cha MK, Lee SW, et al. Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats. Lipids Health Dis. 2011; 10: 116[DOI][PubMed]
  • 72. Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, Niafar M, Asghari-Jafarabadi M, Mofid V, et al. Effect of probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes mellitus. J Dairy Sci. 2011; 94(7): 3288-94[DOI][PubMed]
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments