Advertisement

Modulation of gut microbiome in nonalcoholic fatty liver disease: pro-, pre-, syn-, and antibiotics

  • Min Seok Cho
  • Sang Yeol Kim
  • Ki Tae Suk
  • Byung-Yong Kim
Minireview

Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most common types of liver diseases worldwide and its incidence continues to increase. NAFLD occurs when the body can no longer effectively store excess energy in the adipose tissue. Despite the increasing prevalence of NAFLD, making lifestyle changes, including increased exercise, is often an elusive goal for patients with NAFLD. The liver directly connects to the gut-gastrointestinal milieu via the portal vein, which are all part of the gut-liver axis. Therefore, the gut-microbiome and microbial products have been actively studied as likely key factors in NAFLD pathophysiology. Hence, dysbiosis of the gut microbiome and therapeutic manipulation of the gut-liver axis are being investigated. Novel therapeutic approaches for modulating gut microbiota through the administration of probiotics, prebiotics, synbiotics, and antibiotics have been proposed with numerous promising initial reports on the effectiveness and clinical applications of these approaches. This review delves into the current evidence on novel therapies that modulate gut microbiota and discusses ongoing clinical trials targeting the gut-liver axis for the management and prevention of NAFLD.

Keywords

NAFLD gut-liver axis microbiome probiotics prebiotics synbiotics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abdelmalek, M.F., Suzuki, A., Guy, C., Unalp-Arida, A., Colvin, R., Johnson, R.J., Diehl, A.M., and Nonalcoholic Steatohepatitis Clinical Research Network. 2010. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology 51, 1961–1971.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alisi, A., Bedogni, G., Baviera, G., Giorgio, V., Porro, E., Paris, C., Giammaria, P., Reali, L., Anania, F., and Nobili, V. 2014. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment. Pharmacol. Ther. 39, 1276–1285.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Aller, R., De Luis, D.A., Izaola, O., Conde, R., Gonzalez Sagrado, M., Primo, D., De La Fuente, B., and Gonzalez, J. 2011. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: A double blind randomized clinical trial. Eur. Rev. Med. Pharmacol. Sci. 15, 1090–1095.PubMedGoogle Scholar
  4. Aranha, M.M., Cortez-Pinto, H., Costa, A., da Silva, I.B., Camilo, M.E., de Moura, M.C., and Rodrigues, C.M. 2008. Bile acid levels are increased in the liver of patients with steatohepatitis. Eur. J. Gastroenterol. Hepatol. 20, 519–525.PubMedCrossRefGoogle Scholar
  5. Bajaj, J.S., Heuman, D.M., Hylemon, P.B., Sanyal, A.J., Puri, P., Sterling, R.K., Luketic, V., Stravitz, R.T., Siddiqui, M.S., Fuchs, M., et al. 2014. Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis. Aliment. Pharmacol. Ther. 39, 1113–1125.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bajaj, J.S., Heuman, D.M., Wade, J.B., Gibson, D.P., Saeian, K., Wegelin, J.A., Hafeezullah, M., Bell, D.E., Sterling, R.K., Stravitz, R.T., et al. 2011. Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy. Gastroenterology 140, 478–487.PubMedCrossRefGoogle Scholar
  7. Bajaj, J.S., Idilman, R., Mabudian, L., Hood, M., Fagan, A., Turan, D., White, M.B., Karakaya, F., Wang, J., Atalay, R., et al. 2018. Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort. Hepatology 68, 234–247.PubMedCrossRefGoogle Scholar
  8. Bajaj, J.S., Ridlon, J.M., Hylemon, P.B., Thacker, L.R., Heuman, D.M., Smith, S., Sikaroodi, M., and Gillevet, P.M. 2012. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G168–G175.PubMedCrossRefGoogle Scholar
  9. Bajaj, J.S. and Riggio, O. 2010. Drug therapy: Rifaximin. Hepatology 52, 1484–1488.PubMedCrossRefGoogle Scholar
  10. Bergheim, I., Weber, S., Vos, M., Kramer, S., Volynets, V., Kaserouni, S., McClain, C.J., and Bischoff, S.C. 2008. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: Role of endotoxin. J. Hepatol. 48, 983–992.PubMedCrossRefGoogle Scholar
  11. Bilzer, M., Roggel, F., and Gerbes, A.L. 2006. Role of Kupffer cells in host defense and liver disease. Liver Int. 26, 1175–1186.PubMedCrossRefGoogle Scholar
  12. Bindels, L.B., Porporato, P., Dewulf, E.M., Verrax, J., Neyrinck, A.M., Martin, J.C., Scott, K.P., Buc Calderon, P., Feron, O., Muccioli, G.G., et al. 2012. Gut microbiota-derived propionate reduces cancer cell proliferation in the liver. Br. J. Cancer 107, 1337–1344.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Boursier, J. and Diehl, A.M. 2015. Implication of gut microbiota in nonalcoholic fatty liver disease. PLoS Pathog. 11, e1004559.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Boursier, J., Mueller, O., Barret, M., Machado, M., Fizanne, L., Araujo-Perez, F., Guy, C.D., Seed, P.C., Rawls, J.F., David, L.A., et al. 2016. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 63, 764–775.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Brandl, K., Kumar, V., and Eckmann, L. 2017. Gut-liver axis at the frontier of host-microbial interactions. Am. J. Physiol. Gastrointest. Liver Physiol. 312, G413–G419.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Carr, R.M., Oranu, A., and Khungar, V. 2016. Nonalcoholic fatty liver disease: Pathophysiology and management. Gastroenterol. Clin. North Am. 45, 639–652.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Cassard, A.M. and Ciocan, D. 2018. Microbiota, a key player in alcoholic liver disease. Clin. Mol. Hepatol. 24, 100–107.PubMedCrossRefGoogle Scholar
  18. Chassaing, B., Etienne-Mesmin, L., and Gewirtz, A.T. 2014. Microbiota-liver axis in hepatic disease. Hepatology 59, 328–339.PubMedCrossRefGoogle Scholar
  19. Chavez-Tapia, N.N., Uribe, M., Ponciano-Rodriguez, G., Medina-Santillan, R., and Mendez-Sanchez, N. 2009. New insights into the pathophysiology of nonalcoholic fatty liver disease. Ann. Hepatol. 8 Suppl 1, S9–17.PubMedGoogle Scholar
  20. Chen, Y., Yang, F., Lu, H., Wang, B., Chen, Y., Lei, D., Wang, Y., Zhu, B., and Li, L. 2011. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54, 562–572.PubMedCrossRefGoogle Scholar
  21. Compare, D., Coccoli, P., Rocco, A., Nardone, O.M., De Maria, S., Carteni, M., and Nardone, G. 2012. Gut–liver axis: The impact of gut microbiota on non alcoholic fatty liver disease. Nutr. Metab. Cardiovasc. Dis. 22, 471–476.PubMedCrossRefGoogle Scholar
  22. Cope, K., Risby, T., and Diehl, A.M. 2000. Increased gastrointestinal ethanol production in obese mice: Implications for fatty liver disease pathogenesis. Gastroenterology 119, 1340–1347.PubMedCrossRefGoogle Scholar
  23. Csak, T., Velayudham, A., Hritz, I., Petrasek, J., Levin, I., Lippai, D., Catalano, D., Mandrekar, P., Dolganiuc, A., Kurt-Jones, E., et al. 2011. Deficiency in myeloid differentiation factor-2 and Toll-like receptor 4 expression attenuates nonalcoholic steatohepatitis and fibrosis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 300, G433–441.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Cui, X., Ye, L., Li, J., Jin, L., Wang, W., Li, S., Bao, M., Wu, S., Li, L., Geng, B., et al. 2018. Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients. Sci. Rep. 8, 635.PubMedPubMedCentralCrossRefGoogle Scholar
  25. De Santis, A., Famularo, G., and De Simone, C. 2000. Probiotics for the hemodynamic alterations of patients with liver cirrhosis. Am. J. Gastroenterol. 95, 323–324.PubMedCrossRefGoogle Scholar
  26. Del Chierico, F., Nobili, V., Vernocchi, P., Russo, A., Stefanis, C., Gnani, D., Furlanello, C., Zandona, A., Paci, P., Capuani, G., et al. 2017. Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated metaomics- based approach. Hepatology 65, 451–464.PubMedCrossRefGoogle Scholar
  27. Delzenne, N.M. and Kok, N. 2001. Effects of fructans-type prebiotics on lipid metabolism. Am. J. Clin. Nutr. 73, 456S–458S.PubMedCrossRefGoogle Scholar
  28. Ding, S., Chi, M.M., Scull, B.P., Rigby, R., Schwerbrock, N.M., Magness, S., Jobin, C., and Lund, P.K. 2010. High-fat diet: Bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One 5, e12191.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Dumas, M.E., Barton, R.H., Toye, A., Cloarec, O., Blancher, C., Rothwell, A., Fearnside, J., Tatoud, R., Blanc, V., Lindon, J.C., et al. 2006. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc. Natl. Acad. Sci. USA 103, 12511–12516.PubMedCrossRefGoogle Scholar
  30. Eguchi, S., Takatsuki, M., Hidaka, M., Soyama, A., Ichikawa, T., and Kanematsu, T. 2011. Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation: a prospective randomized study. Am. J. Surg. 201, 498–502.PubMedCrossRefGoogle Scholar
  31. Eslamparast, T., Poustchi, H., Zamani, F., Sharafkhah, M., Malekzadeh, R., and Hekmatdoost, A. 2014. Synbiotic supplementation in nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled pilot study. Am. J. Clin. Nutr. 99, 535–542.PubMedCrossRefGoogle Scholar
  32. Esposito, E., Iacono, A., Bianco, G., Autore, G., Cuzzocrea, S., Vajro, P., Canani, R.B., Calignano, A., Raso, G.M., and Meli, R. 2009. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J. Nutr. 139, 905–911.PubMedCrossRefGoogle Scholar
  33. Etienne-Mesmin, L., Vijay-Kumar, M., Gewirtz, A.T., and Chassaing, B. 2016. Hepatocyte toll-like receptor 5 promotes bacterial clearance and protects mice against high-fat diet-induced liver disease. Cell. Mol. Gastroenterol. Hepatol. 2, 584–604.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Famouri, F., Shariat, Z., Hashemipour, M., Keikha, M., and Kelishadi, R. 2017. Effects of probiotics on non-alcoholic fatty liver disease in obese children and adolescents: A randomized clinical trial. J. Pediatr. Gastroenterol. Nutr. 64, 413–417.PubMedCrossRefGoogle Scholar
  35. Farhadi, A., Gundlapalli, S., Shaikh, M., Frantzides, C., Harrell, L., Kwasny, M.M., and Keshavarzian, A. 2008. Susceptibility to gut leakiness: A possible mechanism for endotoxaemia in non-alcoholic steatohepatitis. Liver Int. 28, 1026–1033.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Gangarapu, V., Ince, A.T., Baysal, B., Kayar, Y., Kilic, U., Gok, O., Uysal, O., and Senturk, H. 2015. Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease. Eur. J. Gastroenterol. Hepatol. 27, 840–845.PubMedCrossRefGoogle Scholar
  37. Garcia-Martinez, I., Santoro, N., Chen, Y., Hoque, R., Ouyang, X., Caprio, S., Shlomchik, M.J., Coffman, R.L., Candia, A., and Mehal, W.Z. 2016. Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9. J. Clin. Invest. 126, 859–864.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Gibson, G.R., Hutkins, R., Sanders, M.E., Prescott, S.L., Reimer, R.A., Salminen, S.J., Scott, K., Stanton, C., Swanson, K.S., Cani, P.D., et al. 2017. Expert consensus document: The international scientific association for probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 14, 491–502.PubMedGoogle Scholar
  39. Gonzalez, F.J., Jiang, C., and Patterson, A.D. 2016. An intestinal microbiota-farnesoid X receptor axis modulates metabolic disease. Gastroenterology 151, 845–859.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Gupta, A. and Khanna, S. 2017. Fecal microbiota transplantation. JAMA 318, 102.PubMedCrossRefGoogle Scholar
  41. Hossain, N., Kanwar, P., and Mohanty, S.R. 2016. A comprehensive updated review of pharmaceutical and nonpharmaceutical treatment for NAFLD. Gastroenterol. Res. Pract. 2016, 7109270.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hutkins, R.W., Krumbeck, J.A., Bindels, L.B., Cani, P.D., Fahey, G. Jr., Goh, Y.J., Hamaker, B., Martens, E.C., Mills, D.A., Rastal, R.A., et al. 2016. Prebiotics: Why definitions matter. Curr. Opin. Biotechnol. 37, 1–7.PubMedCrossRefGoogle Scholar
  43. Jernberg, C., Lofmark, S., Edlund, C., and Jansson, J.K. 2007. Longterm ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 1, 56–66.PubMedCrossRefGoogle Scholar
  44. Jiang, W., Wu, N., Wang, X., Chi, Y., Zhang, Y., Qiu, X., Hu, Y., Li, J., and Liu, Y. 2015. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Sci. Rep. 5, 8096.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Jiang, C., Xie, C., Li, F., Zhang, L., Nichols, R.G., Krausz, K.W., Cai, J., Qi, Y., Fang, Z.Z., Takahashi, S., et al. 2015. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J. Clin. Invest. 125, 386–402.PubMedCrossRefGoogle Scholar
  46. Jirillo, E., Caccavo, D., Magrone, T., Piccigallo, E., Amati, L., Lembo, A., Kalis, C., and Gumenscheimer, M. 2002. The role of the liver in the response to LPS: Experimental and clinical findings. J. Endotoxin. Res. 8, 319–327.PubMedGoogle Scholar
  47. Jones, B.V., Begley, M., Hill, C., Gahan, C.G., and Marchesi, J.R. 2008. Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. Proc. Natl. Acad. Sci. USA 105, 13580–13585.PubMedCrossRefGoogle Scholar
  48. Kundu, P., Blacher, E., Elinav, E., and Pettersson, S. 2017. Our gut microbiome: The evolving inner self. Cell 171, 1481–1493.PubMedCrossRefPubMedCentralGoogle Scholar
  49. Lambert, J.E., Parnell, J.A., Eksteen, B., Raman, M., Bomhof, M.R., Rioux, K.P., Madsen, K.L., and Reimer, R.A. 2015. Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: A randomized controlled trial protocol. BMC Gastroenterol. 15, 169.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Larsen, N., Vogensen, F.K., van den Berg, F.W., Nielsen, D.S., Andreasen, A.S., Pedersen, B.K., Al-Soud, W.A., Sorensen, S.J., Hansen, L.H., and Jakobsen, M. 2010. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5, e9085.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Letexier, D., Diraison, F., and Beylot, M. 2003. Addition of inulin to a moderately high-carbohydrate diet reduces hepatic lipogenesis and plasma triacylglycerol concentrations in humans. Am. J. Clin. Nutr. 77, 559–564.PubMedCrossRefGoogle Scholar
  52. Li, Z., Yang, S., Lin, H., Huang, J., Watkins, P.A., Moser, A.B., Desimone, C., Song, X.Y., and Diehl, A.M. 2003. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 37, 343–350.PubMedCrossRefGoogle Scholar
  53. Lindheim, L., Bashir, M., Munzker, J., Trummer, C., Zachhuber, V., Leber, B., Horvath, A., Pieber, T.R., Gorkiewicz, G., Stadlbauer, V., et al. 2017. Alterations in gut microbiome composition and barrier function are associated with reproductive and metabolic defects in women with polycystic ovary syndrome (PCOS): A pilot study. PLoS One 12, e0168390.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Llorente, C. and Schnabl, B. 2015. The gut microbiota and liver disease. Cell. Mol. Gastroenterol. Hepatol. 1, 275–284.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Loft, S., Sonne, J., Dossing, M., and Andreasen, P.B. 1987. Metronidazole pharmacokinetics in patients with hepatic encephalopathy. Scand. J. Gastroenterol. 22, 117–123.PubMedCrossRefGoogle Scholar
  56. Loguercio, C., De Simone, T., Federico, A., Terracciano, F., Tuccillo, C., Di Chicco, M., and Carteni, M. 2002. Gut-liver axis: A new point of attack to treat chronic liver damage? Am. J. Gastroenterol. 97, 2144–2146.Google Scholar
  57. Lonardo, A., Byrne, C.D., Caldwell, S.H., Cortez-Pinto, H., and Targher, G. 2016. Global epidemiology of nonalcoholic fatty liver disease: Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64, 1388–1389.PubMedCrossRefGoogle Scholar
  58. Lv, L.X., Hu, X.J., Qian, G.R., Zhang, H., Lu, H.F., Zheng, B.W., Jiang, L., and Li, L.J. 2014. Administration of Lactobacillus salivarius LI01 or Pediococcus pentosaceus LI05 improves acute liver injury induced by D-galactosamine in rats. Appl. Microbiol. Biotechnol. 98, 5619–5632.PubMedCrossRefGoogle Scholar
  59. Ma, X., Hua, J., and Li, Z. 2008. Probiotics improve high fat dietinduced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J. Hepatol. 49, 821–830.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Malaguarnera, M., Vacante, M., Antic, T., Giordano, M., Chisari, G., Acquaviva, R., Mastrojeni, S., Malaguarnera, G., Mistretta, A., Li Volti, G., et al. 2012. Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig. Dis. Sci. 57, 545–553.PubMedCrossRefGoogle Scholar
  61. Mas, A., Rodes, J., Sunyer, L., Rodrigo, L., Planas, R., Vargas, V., Castells, L., Rodriguez-Martinez, D., Fernandez-Rodriguez, C., Coll, I., et al. 2003. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: Results of a randomized, double-blind, double-dummy, controlled clinical trial. J. Hepatol. 38, 51–58.PubMedCrossRefGoogle Scholar
  62. Mazzotti, A., Caletti, M.T., Sasdelli, A.S., Brodosi, L., and Marchesini, G. 2016. Pathophysiology of nonalcoholic fatty liver disease: Lifestyle-gut-gene interaction. Dig. Dis. 34 Suppl 1, 3–10.PubMedCrossRefGoogle Scholar
  63. McCullough, A.J. 2004. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin. Liver Dis. 8, 521–533, viii.PubMedCrossRefGoogle Scholar
  64. Mencarelli, A., Cipriani, S., Renga, B., Bruno, A., D’Amore, C., Distrutti, E., and Fiorucci, S. 2012. VSL#3 resets insulin signaling and protects against NASH and atherosclerosis in a model of genetic dyslipidemia and intestinal inflammation. PLoS One 7, e45425.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Miele, L., Marrone, G., Lauritano, C., Cefalo, C., Gasbarrini, A., Day, C., and Grieco, A. 2013. Gut-liver axis and microbiota in NAFLD: Insight pathophysiology for novel therapeutic target. Curr. Pharm. Des. 19, 5314–5324.PubMedCrossRefGoogle Scholar
  66. Miele, L., Valenza, V., La Torre, G., Montalto, M., Cammarota, G., Ricci, R., Masciana, R., Forgione, A., Gabrieli, M.L., Perotti, G., et al. 2009. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 49, 1877–1887.PubMedCrossRefGoogle Scholar
  67. Mofidi, F., Poustchi, H., Yari, Z., Nourinayyer, B., Merat, S., Sharafkhah, M., Malekzadeh, R., and Hekmatdoost, A. 2017. Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: A pilot, randomised, double-blind, placebo-controlled, clinical trial. Br. J. Nutr. 117, 662–668.PubMedCrossRefGoogle Scholar
  68. Mouzaki, M., Comelli, E.M., Arendt, B.M., Bonengel, J., Fung, S.K., Fischer, S.E., McGilvray, I.D., and Allard, J.P. 2013. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 58, 120–127.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Mykhal’chyshyn, H.P., Bodnar, P.M., and Kobyliak, N.M. 2013. Effect of probiotics on proinflammatory cytokines level in patients with type 2 diabetes and nonalcoholic fatty liver disease. Lik. Sprava 2, 56–62.Google Scholar
  70. Nagata, K., Suzuki, H., and Sakaguchi, S. 2007. Common pathogenic mechanism in development progression of liver injury caused by non-alcoholic or alcoholic steatohepatitis. J. Toxicol. Sci. 32, 453–468.PubMedCrossRefGoogle Scholar
  71. Nair, S., Cope, K., Risby, T.H., and Diehl, A.M. 2001. Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis. Am. J. Gastroenterol. 96, 1200–1204.PubMedCrossRefGoogle Scholar
  72. Okubo, H., Sakoda, H., Kushiyama, A., Fujishiro, M., Nakatsu, Y., Fukushima, T., Matsunaga, Y., Kamata, H., Asahara, T., Yoshida, Y., et al. 2013. Lactobacillus casei strain Shirota protects against nonalcoholic steatohepatitis development in a rodent model. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G911–918.PubMedCrossRefGoogle Scholar
  73. Pendyala, S., Neff, L.M., Suarez-Farinas, M., and Holt, P.R. 2011. Diet-induced weight loss reduces colorectal inflammation: Implications for colorectal carcinogenesis. Am. J. Clin. Nutr. 93, 234–242.PubMedCrossRefGoogle Scholar
  74. Pereg, D., Kotliroff, A., Gadoth, N., Hadary, R., Lishner, M., and Kitay-Cohen, Y. 2011. Probiotics for patients with compensated liver cirrhosis: a double-blind placebo-controlled study. Nutrition 27, 177–181.PubMedCrossRefGoogle Scholar
  75. Pineiro, M., Asp, N.G., Reid, G., Macfarlane, S., Morelli, L., Brunser, O., and Tuohy, K. 2008. FAO Technical meeting on prebiotics. J. Clin. Gastroenterol. 42 Suppl 3 Pt 2, S156–159.PubMedCrossRefGoogle Scholar
  76. Pokusaeva, K., Fitzgerald, G.F., and van Sinderen, D. 2011. Carbohydrate metabolism in Bifidobacteria. Genes Nutr. 6, 285–306.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Ponziani, F.R., Scaldaferri, F., Petito, V., Paroni Sterbini, F., Pecere, S., Lopetuso, L.R., Palladini, A., Gerardi, V., Masucci, L., Pompili, M., et al. 2016. The role of antibiotics in gut microbiota modulation: The eubiotic effects of Rifaximin. Dig. Dis. 34, 269–278.PubMedCrossRefGoogle Scholar
  78. Raman, M., Ahmed, I., Gillevet, P.M., Probert, C.S., Ratcliffe, N.M., Smith, S., Greenwood, R., Sikaroodi, M., Lam, V., Crotty, P., et al. 2013. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 11, 868–875, e861–863.PubMedCrossRefGoogle Scholar
  79. Raso, G.M., Simeoli, R., Iacono, A., Santoro, A., Amero, P., Paciello, O., Russo, R., D’Agostino, G., Di Costanzo, M., Canani, R.B., et al. 2014. 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. 25, 81–90.PubMedCrossRefGoogle Scholar
  80. Rayes, N., Seehofer, D., Theruvath, T., Schiller, R.A., Langrehr, J.M., Jonas, S., Bengmark, S., and Neuhaus. P. 2005. Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation–a randomized, double-blind trial. Am. J. Transplant. 5, 125–130.PubMedCrossRefGoogle Scholar
  81. Ridlon, J.M., Kang, D.J., and Hylemon, P.B. 2006. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 47, 241–259.PubMedCrossRefGoogle Scholar
  82. Rinella, M.E. 2015. Nonalcoholic fatty liver disease: A systematic review. JAMA 313, 2263–2273.PubMedCrossRefGoogle Scholar
  83. Rinella, M. and Charlton, M. 2016. The globalization of nonalcoholic fatty liver disease: Prevalence and impact on world health. Hepatology 64, 19–22.PubMedCrossRefGoogle Scholar
  84. Ritze, Y., Bardos, G., Claus, A., Ehrmann, V., Bergheim, I., Schwiertz, A., and Bischoff, S.C. 2014. Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice. PLoS One 9, e80169.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Roberfroid, M., Gibson, G.R., Hoyles, L., McCartney, A.L., Rastall, R., Rowland, I., Wolvers, D., Watzl, B., Szajewska, H., Stahl, B., et al. 2010. Prebiotic effects: Metabolic and health benefits. Br. J. Nutr. 104 Suppl 2, S1–63.PubMedCrossRefGoogle Scholar
  86. Ruiz, A.G., Casafont, F., Crespo, J., Cayon, A., Mayorga, M., Estebanez, A., Fernadez-Escalante, J.C., and Pons-Romero, F. 2007. Lipopolysaccharide-binding protein plasma levels and liver TNFalpha gene expression in obese patients: Evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis. Obes. Surg. 17, 1374–1380.PubMedCrossRefGoogle Scholar
  87. Russell, D.W. 2003. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72, 137–174.PubMedCrossRefGoogle Scholar
  88. Saez-Lara, M.J., Robles-Sanchez, C., Ruiz-Ojeda, F.J., Plaza-Diaz, J., and Gil, A. 2016. Effects of probiotics and synbiotics on obesity, insulin resistance syndrome, type 2 diabetes and non-alcoholic fatty liver disease: A review of human clinical trials. Int. J. Mol. Sci. 17, 928.PubMedCentralCrossRefGoogle Scholar
  89. Sanchez, M., Darimont, C., Drapeau, V., Emady-Azar, S., Lepage, M., Rezzonico, E., Ngom-Bru, C., Berger, B., Philippe, L., Ammon-Zuffrey, C., et al. 2014. Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women. Br. J. Nutr. 111, 1507–1519.PubMedCrossRefGoogle Scholar
  90. Sanyal, A.J., Banas, C., Sargeant, C., Luketic, V.A., Sterling, R.K., Stravitz, R.T., Shiffman, M.L., Heuman, D., Coterrell, A., Fisher, R.A., et al. 2006. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology 43, 682–689.PubMedCrossRefGoogle Scholar
  91. Sanyal, A.J., Chalasani, N., Kowdley, K.V., McCullough, A., Diehl, A.M., Bass, N.M., Neuschwander-Tetri, B.A., Lavine, J.E., Tonascia, J., Unalp, A., et al. 2010. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl. J. Med. 362, 1675–1685.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Sayin, S.I., Wahlstrom, A., Felin, J., Jantti, S., Marschall, H.U., Bamberg, K., Angelin, B., Hyotylainen, T., Oresic, M., and Backhed, F. 2013. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17, 225–235.PubMedCrossRefGoogle Scholar
  93. Schnabl, B. and Brenner, D.A. 2014. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146, 1513–1524.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Seto, W.K. and Yuen, M.F. 2017. Nonalcoholic fatty liver disease in Asia: Emerging perspectives. J. Gastroenterol. 52, 164–174.PubMedCrossRefGoogle Scholar
  95. Shavakhi, A., Minakari, M., Firouzian, H., Assali, R., Hekmatdoost, A., and Ferns, G. 2013. Effect of a probiotic and metformin on liver aminotransferases in non-alcoholic steatohepatitis: A double blind randomized clinical trial. Int. J. Prev. Med. 4, 531–537.PubMedPubMedCentralGoogle Scholar
  96. Soh, S.E, Ong, D.Q., Gerez, I., Zhang, X., Chollate, P., Shek, L.P., Lee, B.W., and Aw, M. 2010. Effect of probiotic supplementation in the first 6 months of life on specific antibody responses to infant Hepatitis B vaccination. Vaccine 28, 2577–2579.PubMedCrossRefGoogle Scholar
  97. Sookoian, S. and Pirola, C.J. 2017. Genetic predisposition in nonalcoholic fatty liver disease. Clin. Mol. Hepatol. 23, 1–12.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Strauss, E., Tramote, R., Silva, E.P., Caly, W.R., Honain, N.Z., Maffei, R.A., and de Sa, M.F. 1992. Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology 39, 542–545.PubMedGoogle Scholar
  99. Suk, K.T., Kim, M.Y., and Baik, S.K. 2014. Alcoholic liver disease: Treatment. World J. Gastroenterol. 20, 12934–12944.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Tarantino, G. and Finelli, C. 2015. Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease. Future Microbiol. 10, 889–902.PubMedCrossRefGoogle Scholar
  101. Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., and Schoonjans, K. 2008. Targeting bile-acid signalling for metabolic diseases. Nat. Rev. Drug Discov. 7, 678–693.PubMedCrossRefGoogle Scholar
  102. Turnbaugh, P.J., Hamady, M., Yatsunenko, T., Cantarel, B.L., Duncan, A., Ley, R.E., Sogin, M.L., Jones, W.J., Roe, B.A., Affourtit, J.P., et al. 2009. A core gut microbiome in obese and lean twins. Nature 457, 480–484.PubMedCrossRefGoogle Scholar
  103. Vajro, P., Mandato, C., Licenziati, M.R., Franzese, A., Vitale, D.F., Lenta, S., Caropreso, M., Vallone, G., and Meli, R. 2011. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J. Pediatr. Gastroenterol. Nutr. 52, 740–743.PubMedCrossRefGoogle Scholar
  104. Verbeke, L., Farre, R., Verbinnen, B., Covens, K., Vanuytsel, T., Verhaegen, J., Komuta, M., Roskams, T., Chatterjee, S., Annaert, P., et al. 2015. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats. Am. J. Pathol. 185, 409–419.PubMedCrossRefGoogle Scholar
  105. Vindigni, S.M. and Surawicz, C.M. 2017. Fecal microbiota transplantation. Gastroenterol. Clin. North Am. 46, 171–185.PubMedCrossRefGoogle Scholar
  106. Vrieze, A., Van Nood, E., Holleman, F., Salojarvi, J., Kootte, R.S., Bartelsman, J.F., Dallinga-Thie, G.M., Ackermans, M.T., Serlie, M.J., Oozeer, R., et al. 2012. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913–916.e7.PubMedCrossRefGoogle Scholar
  107. Wahlstrom, A., Sayin, S.I., Marschall, H.U., and Backhed, F. 2016. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 24, 41–50.PubMedCrossRefGoogle Scholar
  108. Wang, B., Jiang, X., Cao, M., Ge, J., Bao, Q., Tang, L., Chen, Y., and Li, L. 2016. Altered fecal microbiota correlates with liver biochemistry in nonobese patients with non-alcoholic fatty liver disease. Sci. Rep. 6, 32002.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Wang, Z., Klipfell, E., Bennett, B.J., Koeth, R., Levison, B.S., Dugar, B., Feldstein, A.E., Britt, E.B., Fu, X., Chung, Y.M., et al. 2011. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57–63.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Wieland, A., Frank, D.N., Harnke, B., and Bambha, K. 2015. Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease. Aliment. Pharmacol. Ther. 42, 1051–1063.PubMedCrossRefGoogle Scholar
  111. Wiest, R., Albillos, A., Trauner, M., Bajaj, J.S., and Jalan, R. 2017. Targeting the gut-liver axis in liver disease. J. Hepatol. 67, 1084–1103.PubMedCrossRefGoogle Scholar
  112. Wong, V.W., Tse, C.H., Lam, T.T., Wong, G.L., Chim, A.M., Chu, W.C., Yeung, D.K., Law, P.T., Kwan, H.S., Yu, J., et al. 2013. Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis–a longitudinal study. PLoS One 8, e62885.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Woodhouse, C.A., Patel, V.C., Singanayagam, A., and Shawcross, D.L. 2018. Review article: The gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease. Aliment. Pharmacol. Ther. 47, 192–202.PubMedCrossRefGoogle Scholar
  114. Wu, W.C., Zhao, W., and Li, S. 2008. Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats. World J. Gastroenterol. 14, 313–317.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Xie, G., Wang, X., Liu, P., Wei, R., Chen, W., Rajani, C., Hernandez, B.Y., Alegado, R., Dong, B., Li, D., et al. 2016. Distinctly altered gut microbiota in the progression of liver disease. Oncotarget 7, 19355–19366.PubMedPubMedCentralGoogle Scholar
  116. Xu, R.Y., Wan, Y.P., Fang, Q.Y., Lu, W., and Cai, W. 2012. Supplementation with probiotics modifies gut flora and attenuates liver fat accumulation in rat nonalcoholic fatty liver disease model. J. Clin. Biochem. Nutr. 50, 72–77.PubMedCrossRefGoogle Scholar
  117. Xue, L., He, J., Gao, N., Lu, X., Li, M., Wu, X., Liu, Z., Jin, Y., Liu, J., Xu, J., et al. 2017. Probiotics may delay the progression of nonalcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia. Sci. Rep. 7, 45176.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Zhao, Y., Wu, J., Li, J.V., Zhou, N.Y., Tang, H., and Wang, Y. 2013. Gut microbiota composition modifies fecal metabolic profiles in mice. J. Proteome Res. 12, 2987–2999.PubMedCrossRefGoogle Scholar
  119. Zhu, L., Baker, S.S., Gill, C., Liu, W., Alkhouri, R., Baker, R.D., and Gill, S.R. 2013. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH. Hepatology 57, 601–609.PubMedCrossRefPubMedCentralGoogle Scholar
  120. Zhu, L., Baker, R.D., Zhu, R., and Baker, S.S. 2016. Gut microbiota produce alcohol and contribute to NAFLD. Gut 65, 1232.PubMedCrossRefGoogle Scholar

Copyright information

© The Microbiological Society of Korea and Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.ChunLab, Inc.SeoulRepublic of Korea
  2. 2.Division of Gastroenterology and Hepatology, College of MedicineHallym UniversityChuncheonRepublic of Korea

Personalised recommendations