Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

World Journal of Gastroenterology

Volumn 20, Issue 42, 2014, Pages 15518-15531

  Paolella, Giulia ^a   Mandato, Claudia ^b   Pierri, Luca ^a   Poeta, Marco ^a   Di Stasi, Martina ^a   Vajro, Pietro ^a,c  

^a UNIVERSITY OF SALERNO   (Italy)

^b SANTOBONO PAUSILIPON CHILDREN S HOSPITAL   (Italy)

^c European Laboratory for the Investigation of Food Induced Diseases   (Italy)

Author keywords

Bacterial translocation; Barrier function; Gut liver axis; Intestinal microbiota; Non alcoholic fatty liver disease; Probiotics; Small intestinal bacterial overgrowth

Indexed keywords

MEMBRANE PROTEIN; PROBIOTIC AGENT;

ANIMAL MODEL; ANTIBIOSIS; ARTICLE; BACTERIAL OVERGROWTH; CELL MEMBRANE PERMEABILITY; DIETARY INTAKE; FATTY LIVER; GROUPS BY AGE; GUT LIVER AXIS; HUMAN; INTESTINE; INTESTINE EPITHELIUM; INTESTINE FLORA; LIFESTYLE MODIFICATION; LIVER; META ANALYSIS (TOPIC); METABOLIC SYNDROME X; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; OXIDATIVE STRESS; RANDOMIZED CONTROLLED TRIAL (TOPIC); ANIMAL; BACTERIAL TRANSLOCATION; DISEASE MODEL; DYSBIOSIS; HOST PATHOGEN INTERACTION; METABOLISM; MICROBIOLOGY; MICROFLORA; NON-ALCOHOLIC FATTY LIVER DISEASE; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

ANIMALS; BACTERIAL TRANSLOCATION; DISEASE MODELS, ANIMAL; DYSBIOSIS; HOST-PATHOGEN INTERACTIONS; HUMANS; INTESTINES; LIVER; MICROBIOTA; NON-ALCOHOLIC FATTY LIVER DISEASE; PROBIOTICS; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 84912096773     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i42.15518     Document Type: Article

References (98)

1. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 2013; 10: 686-690 [PMID: 24042449 DOI: 10.1038/nrgastro]
2. Compare D, Coccoli P, Rocco A, Nardone OM, De Maria S, Cartenì M, Nardone G. Gut-liver axis: The impact of gut microbiota on non alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2012; 22: 471-476 [PMID: 22546554 DOI: 10.1016/j.numecd.2012.02.007]
3. Miele L, Marrone G, Lauritano C, Cefalo C, Gasbarrini A, Day C, Grieco A. Gut-liver axis and microbiota in NAFLD: Insight pathophysiology for novel therapeutic target. Curr Pharm Des 2013; 19: 5314-5324 [PMID: 23432669]
4. Vajro P, Paolella G, Fasano A. Microbiota and gut-liver axis: Their influences on obesity and obesity-related liver disease. J Pediatr Gastroenterol Nutr 2013; 56: 461-468 [PMID: 23287807 DOI: 10.1097/MPG.0b013e318284abb5]
5. Li DY, Yang M, Edwards S, Ye SQ. Nonalcoholic fatty liver disease: For better or worse, blame the gut microbiota? JPEN J Parenter Enteral Nutr 2013; 37: 787-793 [PMID: 23538296 DOI: 10.1177/0148607113481623]
6. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, Abrams SH, Scheimann AO, Sanyal AJ, Chalasani N, Tonascia J, Ünalp A, Clark JM, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: The TONIC randomized controlled trial. JAMA 2011; 305: 1659-1668 [PMID: 21521847 DOI: 10.1001/jama.2011.520]
7. Nobili V, Svegliati-Baroni G, Alisi A, Miele L, Valenti L, Vajro P. A 360-degree overview of paediatric NAFLD: Recent insights. J Hepatol 2013; 58: 1218-1229 [PMID: 23238106]
8. Sharma V, Garg S, Aggarwal S. Probiotics and liver disease. Perm J 2013; 17: 62-67 [PMID: 24361022 DOI: 10.7812/TPP/12-144]
9. Mehal WZ. The gut-liver axis: A busy two-way street. Hepatology 2012; 55: 1647-1649 [PMID: 22407752 DOI: 10.1002/hep.25704]
10. Guzman JR, Conlin VS, Jobin C. Diet, microbiome, and the intestinal epithelium: An essential triumvirate? Biomed Res Int 2013; 2013: 425146 [PMID: 23586037 DOI: 10.1155/2013/425146]
11. Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC. Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr 2011; 141: 769-776 [PMID: 21430248 DOI: 10.3945/jn.110.135657]
12. Suzuki T. Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci 2013; 70: 631-659 [PMID: 22782113]
13. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9: 799-809 [PMID: 19855405]
14. Marchiando AM, Graham WV, Turner JR. Epithelial barriers in homeostasis and disease. Annu Rev Pathol 2010; 5: 119-144 [PMID: 20078218]
15. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol 2011; 30: 16-34 [PMID: 21235323]
16. Kinnebrew MA, Pamer EG. Innate immune signaling in defense against intestinal microbes. Immunol Rev 2012; 245: 113-131 [PMID: 22168416]
17. Bevins CL, Salzman NH. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 2011; 9: 356-368 [PMID: 21423246]
18. Liévin-Le Moal V, Servin AL. The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: Mucins, antimicrobial peptides, and microbiota. Clin Microbiol Rev 2006; 19: 315-337 [PMID: 16614252]
19. Littman DR, Pamer EG. Role of the commensal microbiota in normal and pathogenic host immune responses. Cell Host Microbe 2011; 10: 311-323 [PMID: 22018232]
20. Kamada N, Seo SU, Chen GY, Núñez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol 2013; 13: 321-335 [PMID: 23618829 DOI: 10.1038/nri3430]
21. Stecher B, Maier L, Hardt WD. Blooming' in the gut: How dysbiosis might contribute to pathogen evolution. Nat Rev Microbiol 2013; 11: 277-284 [PMID: 23474681]
22. Holzapfel WH, Haberer P, Snel J, Schillinger U, Huis in't Veld JH. Overview of gut flora and probiotics. Int J Food Microbiol 1998; 41: 85-101 [PMID: 9704859]
23. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev 2010; 90: 859-904 [PMID: 20664075 DOI: 10.1152/physrev.00045.2009]
24. Guaraldi F, Salvatori G. Effect of breast and formula feeding on gut microbiota shaping in newborns. Front Cell Infect Microbiol 2012; 2: 94 [PMID: 23087909 DOI: 10.3389/fcimb.2012.00094]
25. Shen J, Obin MS, Zhao L. The gut microbiota, obesity and insulin resistance. Mol Aspects Med 2013; 34: 39-58 [PMID: 23159341 DOI: 10.1016/j.mam.2012.11.001]
26. Bervoets L, Van Hoorenbeeck K, Kortleven I, Van Noten C, Hens N, Vael C, Goossens H, Desager KN, Vankerckhoven V. Differences in gut microbiota composition between obese and lean children: A cross-sectional study. Gut Pathog 2013; 5: 10 [PMID: 23631345 DOI: 10.1186/1757-4749-5-10]
27. Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Mascianà R, Forgione A, Gabrieli ML, Perotti G, Vecchio FM, Rapaccini G, Gasbarrini G, Day CP, Grieco A. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 2009; 49: 1877-1887 [PMID: 19291785 DOI: 10.1002/hep.22848]
28. Teixeira TF, Collado MC, Ferreira CL, Bressan J, Peluzio Mdo C. Potential mechanisms for the emerging link between obesity and increased intestinal permeability. Nutr Res 2012; 32: 637-647 [PMID: 23084636]
29. Payne AN, Chassard C, Zimmermann M, Müller P, Stinca S, Lacroix C. The metabolic activity of gut microbiota in obese children is increased compared with normal-weight children and exhibits more exhaustive substrate utilization. Nutr Diabetes 2011; 1: E12 [PMID: 23154580 DOI: 10.1038/nutd.2011.8]
30. 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: 1027-1031 [PMID: 17183312 DOI: 10.1038/nature05414]
31. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. A core gut microbiome in obese and lean twins. Nature 2009; 457: 480-484 [PMID: 19043404]
32. Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, McGilvray ID, Allard JP. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 2013; 58: 120-127 [PMID: 23401313 DOI: 10.1002/hep.26319]
33. Armougom F, Henry M, Vialettes B, Raccah D, Raoult D. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS One 2009; 4: E7125 [PMID: 19774074 DOI: 10.1371/journal.pone.0007125]
34. Million M, Maraninchi M, Henry M, Armougom F, Richet H, Carrieri P, Valero R, Raccah D, Vialettes B, Raoult D. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes (Lond) 2012; 36: 817-825 [PMID: 21829158 DOI: 10.1038/ijo.2011.153]
35. Nadal I, Santacruz A, Marcos A, Warnberg J, Garagorri JM, Moreno LA, Martin-Matillas M, Campoy C, Martí A, Moleres A, Delgado M, Veiga OL, García-Fuentes M, Redondo CG, Sanz Y. Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int J Obes (Lond) 2009; 33: 758-767 [PMID: 19050675 DOI: 10.1038/ijo.2008.260]
36. Santacruz A, Marcos A, Wärnberg J, Martí A, Martin-Matillas M, Campoy C, Moreno LA, Veiga O, Redondo-Figuero C, Garagorri JM, Azcona C, Delgado M, García-Fuentes M, Collado MC, Sanz Y. Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity (Silver Spring) 2009; 17: 1906-1915 [PMID: 19390523 DOI: 10.1038/oby.2009.112]
37. Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE, Krajmalnik-Brown R. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA 2009; 106: 2365-2370 [PMID: 19164560 DOI: 10.1073/pnas.0812600106]
38. Wong VW, Tse CH, Lam TT, Wong GL, Chim AM, Chu WC, Yeung DK, Law PT, Kwan HS, Yu J, Sung JJ, Chan HL. Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis-A longitudinal study. PLoS One 2013; 8: E62885 [PMID: 23638162 DOI: 10.1371/journal. pone.0062885]
39. Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, Gill SR. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH. Hepatology 2013; 57: 601-609 [PMID: 23055155 DOI: 10.1002/hep.26093]
40. Schwiertz A, Taras D, Schäfer K, Beijer S, Bos NA, Donus C, Hardt PD. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 2010; 18: 190-195 [PMID: 19498350 DOI: 10.1038/oby.2009.167]
41. Raman M, Ahmed I, Gillevet PM, Probert CS, Ratcliffe NM, Smith S, Greenwood R, Sikaroodi M, Lam V, Crotty P, Bailey J, Myers RP, Rioux KP. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2013; 11: 868-75.e1-3 [PMID: 23454028 DOI: 10.1016/j.cgh.2013.02.015]
42. Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, Almeida M, Quinquis B, Levenez F, Galleron N, Gougis S, Rizkalla S, Batto JM, Renault P, Doré J, Zucker JD, Clément K, Ehrlich SD. Dietary intervention impact on gut microbial gene richness. Nature 2013; 500: 585-588 [PMID: 23985875 DOI: 10.1038/nature12480]
43. Chassaing B, Gewirtz AT. Gut microbiota, low-grade inflammation, and metabolic syndrome. Toxicol Pathol 2014; 42: 49-53 [PMID: 24285672 DOI: 10.1002/hep.26494]
44. Macfarlane GT, Macfarlane S. Fermentation in the human large intestine: Its physiologic consequences and the potential contribution of prebiotics. J Clin Gastroenterol 2011; 45 Suppl: S120-S127 [PMID: 21992950 DOI: 10.1097/MCG.0b013e31822fecfe]
45. Giorgio V, Miele L, Principessa L, Ferretti F, Villa MP, Negro V, Grieco A, Alisi A, Nobili V. Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with liver disease severity. Dig Liver Dis 2014; 46: 556-560 [PMID: 24631029 DOI: 10.1016/j.dld.2014.02.010]
46. Smits LP, Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology 2013; 145: 946-953 [PMID: 24018052 DOI: 10.1053/j.gastro.2013.08.058]
47. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013; 341: 1241214 [PMID: 24009397 DOI: 10.1126/science.1241214]
48. Kesar V, Odin JA. Toll-like receptors and liver disease. Liver Int 2014; 34: 184-196 [PMID: 24118797 DOI: 10.1111/liv.12315]
49. Mehal WZ. The Gordian Knot of dysbiosis, obesity and NAFLD. Nat Rev Gastroenterol Hepatol 2013; 10: 637-644 [PMID: 23958600 DOI: 10.1038/nrgastro.2013.146]
50. Cario E. Barrier-protective function of intestinal epithelial Toll-like receptor 2. Mucosal Immunol 2008; 1 Suppl 1: S62-S66 [PMID: 19079234 DOI: 10.1038/mi.2008.47]
51. Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 2010; 328: 228-231 [PMID: 20203013 DOI: 10.1126/science.1179721]
52. Requena T, Shahar DR, Kleiveland CR, Martínez-Cuesta MC, Peláez C, Lea T. Interactions between gut microbiota, food and the obese host. Rends Food Sci Tech 2013; 34: 44-53 [DOI: 10.1016/j.tifs.2013.08.007]
53. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, Thaiss CA, Kau AL, Eisenbarth SC, Jurczak MJ, Camporez JP, Shulman GI, Gordon JI, Hoffman HM, Flavell RA. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012; 482: 179-185 [PMID: 22297845 DOI: 10.1038/nature10809]
54. Ouwehand A, Forssten S, Lehtinen M, Galbraith E, Davis E. Probiotic lactic acid bacteria vs bacilli: Pros and cons. Agro Food Ind Hi Tec 2013; 24: 13-18 55 Govender M, Choonara YE, Kumar P, du Toit LC, van Vuuren S, Pillay V. A review of the advancements in probiotic delivery: Conventional vs. non-conventional formulations for intestinal flora supplementation. AAPS PharmSciTech 2014; 15: 29-43 [PMID: 24222267 DOI: 10.1208/s12249-013-0027-1]
55. Resta-Lenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut 2003; 52: 988-997 [PMID: 12801956]
56. Yan F, Polk DB. Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem 2002; 277: 50959-50965 [PMID: 12393915]
57. Ewaschuk JB, Diaz H, Meddings L, Diederichs B, Dmytrash A, Backer J, Looijer-van Langen M, Madsen KL. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol Gastrointest Liver Physiol 2008; 295: G1025-G1034 [PMID: 18787064 DOI: 10.1152/ajpgi. 90227.2008]
58. 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: 804-816 [PMID: 17087734]
59. Parassol N, Freitas M, Thoreux K, Dalmasso G, Bourdet-Sicard R, Rampal P. Lactobacillus casei DN-114 001 inhibits the increase in paracellular permeability of enteropathogenic Escherichia coli-infected T84 cells. Res Microbiol 2005; 156: 256-262 [PMID: 15748992]
60. Otte JM, Podolsky DK. Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. Am J Physiol Gastrointest Liver Physiol 2004; 286: G613-G626 [PMID: 15010363]
61. Karczewski J, Troost FJ, Konings I, Dekker J, Kleerebezem M, Brummer RJ, Wells JM. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Gastrointest Liver Physiol 2010; 298: G851-G859 [PMID: 20224007 DOI: 10.1152/ajpgi.00327.2009]
62. 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 [PMID: 12540784]
63. 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 [PMID: 19321579 DOI: 10.3945/jn.108.101808]
64. 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 [PMID: 18674841 DOI: 10.1016/j.jhep.2008.05.025]
65. 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 [PMID: 19115316 DOI: 10.1002/hep.22711]
66. Mencarelli A, Cipriani S, Renga B, Bruno A, D'Amore C, Distrutti E, Fiorucci S. VSL#3 resets insulin signaling and protects against NASH and atherosclerosis in a model of genetic dyslipidemia and intestinal inflammation. PLoS One 2012; 7: E45425 [PMID: 23029000 DOI: 10.1371/journal.pone.0045425]
67. Bhathena J, Martoni C, Kulamarva A, Tomaro-Duchesneau C, Malhotra M, Paul A, Urbanska AM, Prakash S. Oral probiotic microcapsule formulation ameliorates non-alcoholic fatty liver disease in Bio F1B Golden Syrian hamsters. PLoS One 2013; 8: E58394 [PMID: 23554890 DOI: 10.1371/journal. pone.0058394]
68. Wagnerberger S, Spruss A, Kanuri G, Stahl C, Schröder M, Vetter W, Bischoff SC, Bergheim I. Lactobacillus casei Shirota protects from fructose-induced liver steatosis: A mouse model. J Nutr Biochem 2013; 24: 531-538 [PMID: 22749137 DOI: 10.1016/j.jnutbio.2012.01.014]
69. Karahan N, Isler M, Koyu A, Karahan AG, Basyigit Kiliç G, Ciris IM, Sütçü R, Onaran I, Cam H, Keskin M. Effects of probiotics on methionine choline deficient diet-induced steatohepatitis in rats. Turk J Gastroenterol 2012; 23: 110-121 [PMID: 22706738]
70. Yalçin SS, Güçer S, Yalçin S, Onbasilar I, Kale G, Coskun T. Effects of probiotic (Primalac 454) on nonalcoholic fatty liver disease in broilers. Revue Méd Vét 2011; 7: 371-376
71. Xu RY, Wan YP, Fang QY, Lu W, Cai W. Supplementation with probiotics modifies gut flora and attenuates liver fat accumulation in rat nonalcoholic fatty liver disease model. J Clin Biochem Nutr 2012; 50: 72-77 [PMID: 22247604 DOI: 10.3164/jcbn.11-38]
72. Vajro P, Mandato C, Licenziati MR, Franzese A, Vitale DF, Lenta S, Caropreso M, Vallone G, Meli R. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr 2011; 52: 740-743 [PMID: 21505361 DOI: 10.1097/MPG.0b013e31821f9b85]
73. Nardone G, Compare D, Liguori E, Di Mauro V, Rocco A, Barone M, Napoli A, Lapi D, Iovene MR, Colantuoni A. 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 [PMID: 20576921 DOI: 10.1152/ajpgi.00188.2010]
74. 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. Iran J Diab Lipid Disorders 2010; 9: 1-7
75. Raso GM, Simeoli R, Iacono A, Santoro A, Amero P, Paciello O, Russo R, D'Agostino G, Di Costanzo M, Canani RB, Calignano A, Meli R. Effects of a Lactobacillus paracasei B21060 based synbiotic on steatosis, insulin signaling and toll-like receptor expression in rats fed a high-fat diet. J Nutr Biochem 2014; 25: 81-90 [PMID: 24314869 DOI: 10.1016/j.jnutbio.2013.09.006]
76. Endo H, Niioka M, Kobayashi N, Tanaka M, Watanabe T. Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: New insight into the probiotics for the gut-liver axis. PLoS One 2013; 8: E63388 [PMID: 23696823 DOI: 10.1371/journal.pone.0063388]
77. Chiua YH, Linb SL, Oua CC, Lue YC, Huanga HY, Lina MY. Anti-inflammatory effect of lactobacilli bacteria on HepG2 cells is through cross-regulation of TLR4 and NOD2 signalling. J Funct Foods 2013; 5: 820-828. Available from: URL: Http://www.sciencedirect.com/science/article/pii/S1756464613000467
78. Konishi H, Fujiya M, Kohgo Y. Traffic control of bacteriaderived molecules: A new system of host-bacterial crosstalk. Int J Cell Biol 2013; 2013: 757148 [PMID: 23606846 DOI: 10.1155/2013/757148]
79. Lirussi F, Mastropasqua E, Orando S, Orlando R. Probiotics for non-alcoholic fatty liver disease and/or steatohepatitis. Cochrane Database Syst Rev 2007; (1): CD005165 [PMID: 17253543]
80. Loguercio C, De Simone T, Federico A, Terracciano F, Tuccillo C, Di Chicco M, Cartenì M. Gut-liver axis: A new point of attack to treat chronic liver damage? Am J Gastroenterol 2002; 97: 2144-2146 [PMID: 12190198]
81. 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 [PMID: 15942443]
82. Socha P, Horvath A, Vajro P, Dziechciarz P, Dhawan A, Szajewska H. Pharmacological interventions for nonalcoholic fatty liver disease in adults and in children: A systematic review. J Pediatr Gastroenterol Nutr 2009; 48: 587-596 [PMID: 19412008 DOI: 10.1097/MPG.0b013e31818e04d1]
83. Solga SF, Buckley G, Clark JM, Horska A, Diehl AM. The effect of a probiotic on hepatic steatosis. J Clin Gastroenterol 2008; 42: 1117-1119 [PMID: 18936646]
84. Aller R, De Luis DA, Izaola O, Conde R, Gonzalez Sagrado M, Primo D, De La Fuente B, Gonzalez J. 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 [PMID: 22013734]
85. Malaguarnera M, Vacante M, Antic T, Giordano M, Chisari G, Acquaviva R, Mastrojeni S, Malaguarnera G, Mistretta A, Li Volti G, Galvano F. Bifidobacterium longum with fructooligosaccharides in patients with non alcoholic steatohepatitis. Dig Dis Sci 2012; 57: 545-553 [PMID: 21901256 DOI: 10.1007/s10620-011-1887-4]
86. Wong VW, Won GL, Chim AM, Chu WC, Yeung DK, Li KC, Chan HL. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann Hepatol 2013; 12: 256-262 [PMID: 23396737]
87. 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 [PMID: 24187469 DOI: 10.3748/wjg.v19.i40.6911]
88. Eslamparast T, Poustchi H, Zamani F, Sharafkhah M, Malekzadeh R, Hekmatdoost A. Synbiotic supplementation in nonalcoholic fatty liver disease: A randomized, doubleblind, placebo-controlled pilot study. Am J Clin Nutr 2014; 99: 535-542 [PMID: 24401715 DOI: 10.3945/ajcn.113.068890]
89. Alisi A, Bedogni G, Baviera G, Giorgio V, Porro E, Paris C, Giammaria P, Reali L, Anania F, Nobili V. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2014; 39: 1276-1285 [PMID: 24738701 DOI: 10.1111/apt.12758]
90. Shavakhi A, Minakari M, Firouzian H, Assali R, Hekmatdoost A, Ferns G. Effect of a Probiotic and Metformin on Liver Aminotransferases in Non-alcoholic Steatohepatitis: A Double Blind Randomized Clinical Trial. Int J Prev Med 2013; 4: 531-537 [PMID: 23930163]
91. Parnell JA, Raman M, Rioux KP, Reimer RA. The potential role of prebiotic fibre for treatment and management of nonalcoholic fatty liver disease and associated obesity and in-sulin resistance. Liver Int 2012; 32: 701-711 [PMID: 22221818 DOI: 10.1111/j.1478-3231.2011.02730.x]
92. Kleessen B, Schwarz S, Boehm A, Fuhrmann H, Richter A, Henle T, Krueger M. Jerusalem artichoke and chicory inulin in bakery products affect faecal microbiota of healthy volunteers. Br J Nutr 2007; 98: 540-549 [PMID: 17445348]
93. Vajro P, Lenta S, Pignata C, Salerno M, D'Aniello R, De Micco I, Paolella G, Parenti G. Therapeutic options in pediatric non alcoholic fatty liver disease: Current status and future directions. Ital J Pediatr 2012; 38: 55 [PMID: 23075296 DOI: 10.1186/1824-7288-38-55]
94. Vajro P, Paolella G, Poeta M, Pizza C, Sangermano M, Massa G. Pediatric non alcoholic fatty liver disease: More on novel treatment targets. BMC Pediatr 2013; 13: 109 [PMID: 23870449 DOI: 10.1186/1471-2431-13-109]
95. Younossi ZM, Reyes MJ, Mishra A, Mehta R, Henry L. Systematic review with meta-analysis: Non-alcoholic steatohepatitis -A case for personalised treatment based on pathogenic targets. Aliment Pharmacol Ther 2014; 39: 3-14 [PMID: 24206433 DOI: 10.1111/apt.12543]
96. Volynets V, Machann J, Küper MA, Maier IB, Spruss A, Königsrainer A, Bischoff SC, Bergheim I. A moderate weight reduction through dietary intervention decreases hepatic fat content in patients with non-alcoholic fatty liver disease (NAFLD): A pilot study. Eur J Nutr 2013; 52: 527-535 [PMID: 22543623 DOI: 10.1007/s00394-012-0355-z]
97. Vajro P, Poeta M, Pierri L, Pizza C, D'Aniello R, Sangermano M, Massa M, Paolella G. Probiotics to Treat Visceral Obesity and Related Liver Disease. In: Watson RR. Editor "Nutrition in the Prevention and Treatment of Abdominal Obesity". London: Academic Press, 2014: 363-380
98. Ong JP, Younossi ZM. Editorial: Probiotics in NASH -more studies are needed. Aliment Pharmacol Ther 2014; 40: 211-212 [PMID: 24946062 DOI: 10.1111/apt.12812]