Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The role of the gut microbiota in NAFLD

Key Points

  • The incidence of fatty liver disease, and its complications of inflammation, fibrosis and liver cancer, is increasing

  • Gut dysbiosis (an unhealthy gut microbiota) contributes to the pathogenesis of obesity-related disorders including the metabolic syndrome and NAFLD

  • Considerable differences exist between individuals' microbiota, influenced by the perinatal environment, diet, antibiotic exposure and lifestyle factors; changes in these factors might lead to the development of dysbiosis

  • The gut that is compromised by dysbiosis is a portal for increased exposure of the liver to bacteria, bacterial products and injurious components of foods that contribute to NAFLD pathogenesis

  • Improved methods of analysis to define healthy and unhealthy microbiotas, and better understanding of dietary and other factors that influence the gut–liver axis will facilitate preventive strategies and treatments for this disease

Abstract

NAFLD is now the most common cause of liver disease in Western countries. This Review explores the links between NAFLD, the metabolic syndrome, dysbiosis, poor diet and gut health. Animal studies in which the gut microbiota are manipulated, and observational studies in patients with NAFLD, have provided considerable evidence that dysbiosis contributes to the pathogenesis of NAFLD. Dysbiosis increases gut permeability to bacterial products and increases hepatic exposure to injurious substances that increase hepatic inflammation and fibrosis. Dysbiosis, combined with poor diet, also changes luminal metabolism of food substrates, such as increased production of certain short-chain fatty acids and alcohol, and depletion of choline. Changes to the microbiome can also cause dysmotility, gut inflammation and other immunological changes in the gut that might contribute to liver injury. Evidence also suggests that certain food components and lifestyle factors, which are known to influence the severity of NAFLD, do so at least in part by changing the gut microbiota. Improved methods of analysis of the gut microbiome, and greater understanding of interactions between dysbiosis, diet, environmental factors and their effects on the gut–liver axis should improve the treatment of this common liver disease and its associated disorders.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Key mechanistic pathways involved in the gut–liver axis in NAFLD progression.

Similar content being viewed by others

References

  1. Loomba, R. & Sanyal, A. J. The global NAFLD epidemic. Nat. Rev. Gastroenterol. Hepatol. 10, 686–690 (2013).

    CAS  PubMed  Google Scholar 

  2. Farrell, G. C. & Larter, C. Z. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43, S99–S112 (2006).

    CAS  PubMed  Google Scholar 

  3. Wong, R. J., Cheung, R. & Ahmed, A. Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology 59, 2188–2195 (2014).

    PubMed  Google Scholar 

  4. Basaranoglu, M., Basaranoglu, G. & Sentürk, H. From fatty liver to fibrosis: a tale of 'second hit'. World J. Gastroenterol. 19, 1158 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Manti, S. et al. Nonalcoholic fatty liver disease/non-alcoholic steatohepatitis in childhood: endocrine-metabolic 'mal-programming'. Hepat. Mon. 14, e17641 (2014).

    PubMed  PubMed Central  Google Scholar 

  6. Williams, C. D. et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 140, 124–131 (2011).

    PubMed  Google Scholar 

  7. Mouzaki, M. & Allard, J. P. The role of nutrients in the development, progression, and treatment of nonalcoholic fatty liver disease. J. Clin. Gastroenterol. 46, 457–467 (2012).

    PubMed  Google Scholar 

  8. Goodwin, M. et al. Advanced glycation end products augment experimental hepatic fibrosis. J. Gastroenterol. Hepatol. 28, 369–376 (2013).

    CAS  PubMed  Google Scholar 

  9. Tarantino, G., Savastano, S. & Colao, A. Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance. World J. Gastroenterol. 16, 4773–4783 (2010).

    PubMed  PubMed Central  Google Scholar 

  10. Compare, D. et al. Gut–liver axis: the impact of gut microbiota on non alcoholic fatty liver disease. Nutr. Metab. Cardiovasc. Dis. 22, 471–476 (2012).

    CAS  PubMed  Google Scholar 

  11. Volynets, V. et al. Nutrition, intestinal permeability, and blood ethanol levels are altered in patients with nonalcoholic fatty liver disease (NAFLD). Dig. Dis. Sci. 57, 1932–1941 (2012).

    CAS  PubMed  Google Scholar 

  12. Backhed, F. in A Systems Biology Approach to Study Metabolic Syndrome (eds Oresic, M. & Vidal-Puig, A.) 171–181 (Springer International Publishing AG, 2014).

    Google Scholar 

  13. Rinella, M. E. & Sanyal, A. J. NAFLD in 2014: genetics, diagnostics and therapeutic advances in NAFLD. Nat. Rev. Gastroenterol. Hepatol. 12, 65–66 (2015).

    PubMed  PubMed Central  Google Scholar 

  14. Khalid, Q., Bailey, I. & Patel, V. Non-Al-coholic fatty liver disease: the effect of bile acids and farnesoid X recep-tor agonists on pathophysiology and treatment. Liver Res. Open J. 1, 32–40 (2015).

    Google Scholar 

  15. Ursell, L. K. et al. The interpersonal and intrapersonal diversity of human-associated microbiota in key body sites. J. Allergy Clin. Immunol. 129, 1204–1208 (2012).

    PubMed  PubMed Central  Google Scholar 

  16. The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

  17. Tremaroli, V. & Backhed, F. Functional interactions between the gut microbiota and host metabolism. Nature 489, 242–249 (2012).

    CAS  PubMed  Google Scholar 

  18. Reinhardt, C., Reigstad, C. S. & Bäckhed, F. Intestinal microbiota during infancy and its implications for obesity. J. Pediatr. Gastroenterol. Nutr. 48, 249–256 (2009).

    PubMed  Google Scholar 

  19. Cox, L. M. et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158, 705–721 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. White, D. G. et al. The isolation of antibiotic-resistant Salmonella from retail ground meats. N. Engl. J. Med. 345, 1147–1154 (2001).

    CAS  PubMed  Google Scholar 

  21. Loftus, E. V. et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 54, 91–96 (2005).

    PubMed  PubMed Central  Google Scholar 

  22. Wigg, A. et al. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor α in the pathogenesis of non-alcoholic steatohepatitis. Gut 48, 206–211 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1131 (2006).

    PubMed  Google Scholar 

  24. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).

    CAS  PubMed  Google Scholar 

  25. Membrez, M. et al. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J. 22, 2416–2426 (2008).

    CAS  PubMed  Google Scholar 

  26. Mazagova, M. et al. Commensal microbiota is hepatoprotective and prevents liver fibrosis in mice. FASEB J. 29, 1043–1055 (2015).

    CAS  PubMed  Google Scholar 

  27. Cho, I. et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488, 621–626 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Vrieze, A. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913–916.e7 (2012).

    CAS  PubMed  Google Scholar 

  29. Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

    CAS  PubMed  Google Scholar 

  30. Siddiqui, M. S. et al. Severity of nonalcoholic fatty liver disease and progression to cirrhosis are associated with atherogenic lipoprotein profile. Clin. Gastroenterol. Hepatol. 13, 1000–1008.e3 (2015).

    CAS  PubMed  Google Scholar 

  31. Stams, A. J. M. & Plugge, C. M. Electron transfer in syntrophic communities of anaerobic bacteria and archaea. Nat. Rev. Microbiol. 7, 568–577 (2009).

    CAS  PubMed  Google Scholar 

  32. Sinal, C. J. et al. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102, 731–744 (2000).

    CAS  PubMed  Google Scholar 

  33. Carr, R. M. & Reid, A. E. FXR agonists as therapeutic agents for non-alcoholic fatty liver disease. Curr. Atheroscler. Rep. 17, 1–14 (2015).

    CAS  Google Scholar 

  34. Neuschwander-Tetri, B. A. et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385, 956–965 (2015).

    CAS  PubMed  Google Scholar 

  35. Musso, G., Cassader, M. & Gambino, R. Trials of obeticholic acid for non-alcoholic steatohepatitis. Lancet 386, 27 (2015).

    PubMed  Google Scholar 

  36. Armstrong, M. J. & Newsome, P. N. Trials of obeticholic acid for non-alcoholic steatohepatitis. Lancet 386, 28 (2015).

    PubMed  Google Scholar 

  37. Jiang, C. et al. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J. Clin. Invest. 125, 386–402 (2015).

    PubMed  Google Scholar 

  38. Tuominen, I. & Beaven, S. W. Intestinal farnesoid X receptor puts a fresh coat of wax on fatty liver. Hepatology 62, 646–648 (2015).

    PubMed  PubMed Central  Google Scholar 

  39. Duncan, S. H., Louis, P., Thomson, J. M. & Flint, H. J. The role of pH in determining the species composition of the human colonic microbiota. Environ. Microbiol. 11, 2112–2122 (2009).

    PubMed  Google Scholar 

  40. Arslan, N. Obesity, fatty liver disease and intestinal microbiota. World J. Gastroenterol. 20, 16452–16463 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Hara, H., Haga, S., Aoyama, Y. & Kiriyama, S. Short-chain fatty acids suppress cholesterol synthesis in rat liver and intestine. J. Nutr. 129, 942–948 (1999).

    CAS  PubMed  Google Scholar 

  42. den Besten, G. et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARγ-dependent switch from lipogenesis to fat oxidation. Diabetes 64, 2398–2408 (2015).

    CAS  PubMed  Google Scholar 

  43. Brüssow, H. & Parkinson, S. J. You are what you eat. Nat. Biotechnol. 32, 243–245 (2014).

    PubMed  Google Scholar 

  44. Subramanian, S. et al. Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice. J. Lipid Res. 52, 1626–1635 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Wostmann, B. S., Larkin, C., Moriarty, A. & Bruckner-Kardoss, E. Dietary intake, energy metabolism, and excretory losses of adult male germfree Wistar rats. Lab. Anim. Sci. 33, 46–50 (1983).

    CAS  PubMed  Google Scholar 

  46. Webb, P. & Annis, J. Adaptation to overeating in lean and overweight men and women. Hum. Nutr. Clin. Nutr. 37, 117–131 (1983).

    CAS  PubMed  Google Scholar 

  47. Jumpertz, R. et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am. J. Clin. Nutr. 94, 58–65 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Mouzaki, M. et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 58, 120–127 (2013).

    CAS  PubMed  Google Scholar 

  49. De Wit, N. et al. Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 303, G589–G599 (2012).

    CAS  PubMed  Google Scholar 

  50. Boursier, J. & Diehl, A. M. Implication of gut microbiota in nonalcoholic fatty liver disease. PLoS Pathog. 11, e1004559 (2015).

    PubMed  PubMed Central  Google Scholar 

  51. Alkhouri, N. et al. Development and validation of a new histological score for pediatric non-alcoholic fatty liver disease. J. Hepatol. 57, 1312–1318 (2012).

    PubMed  Google Scholar 

  52. Wong, V. et al. Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis — a longitudinal study. PLoS ONE 8, e62885 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Raman, M. et al. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 11, 868–875.e3 (2013).

    CAS  PubMed  Google Scholar 

  54. Jiang, W. et al. 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 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhu, L. et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology 57, 601–609 (2013).

    CAS  PubMed  Google Scholar 

  56. Musso, G., Gambino, R. & Cassader, M. Obesity, diabetes, and gut microbiota the hygiene hypothesis expanded? Diabetes Care 33, 2277–2284 (2010).

    PubMed  PubMed Central  Google Scholar 

  57. Svegliati-Baroni, G. et al. Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis. Liver Int. 31, 1285–1297 (2011).

    CAS  PubMed  Google Scholar 

  58. Ulven, T. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Front. Endocrinol. (Lausanne) 3, 111 (2012).

    Google Scholar 

  59. Bollrath, J., & Powrie, F. Feed your Tregs more fiber. Science 341, 463–464 (2013).

    CAS  PubMed  Google Scholar 

  60. Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).

    CAS  PubMed  Google Scholar 

  61. Delaere, F. et al. The role of sodium-coupled glucose co-transporter 3 in the satiety effect of portal glucose sensing. Mol. Metab. 2, 47–53 (2013).

    CAS  Google Scholar 

  62. Troy, S. et al. Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice. Cell Metab. 8, 201–211 (2008).

    CAS  PubMed  Google Scholar 

  63. Bäckhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004).

    PubMed  Google Scholar 

  64. Alex, S. et al. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ. Mol. Cell Biol. 33, 1303–1316 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Trinchese, G. et al. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota. J. Nutr. Biochem. 26, 1136–1146 (2015).

    CAS  PubMed  Google Scholar 

  66. Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761–1772 (2007).

    CAS  PubMed  Google Scholar 

  67. Mao, J.-W. et al. Intestinal mucosal barrier dysfunction participates in the progress of nonalcoholic fatty liver disease. Int. J. Clin. Exp. Pathol. 8, 3648–3658 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Kohjima, M. et al. SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int. J. Mol. Med. 21, 507–511 (2008).

    CAS  PubMed  Google Scholar 

  69. Hur, W. et al. Downregulation of microRNA-451 in non-alcoholic steatohepatitis inhibits fatty acid-induced proinflammatory cytokine production through the AMPK/AKT pathway. Int. J. Biochem. Cell Biol. 64, 265–276 (2015).

    CAS  PubMed  Google Scholar 

  70. Zhang, M. et al. Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease. J. Nutr. Biochem. 26, 337–344 (2015).

    CAS  PubMed  Google Scholar 

  71. Than, N. N. & Newsome, P. N. A concise review of non-alcoholic fatty liver disease. Atherosclerosis 239, 192–202 (2015).

    CAS  PubMed  Google Scholar 

  72. Mencin, A., Kluwe, J. & Schwabe, R. F. Toll-like receptors as targets in chronic liver diseases. Gut 58, 704–720 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Federico, A., Dallio, M., Godos, J., Loguercio, C. & Salomone, F. Targeting gut–liver axis for the treatment of nonalcoholic steatohepatitis: translational and clinical evidence. Transl. Res. 167, 116–124 (2016).

    CAS  PubMed  Google Scholar 

  74. Friedman, S. L. A deer in the headlights: BAMBI meets liver fibrosis. Nat. Med. 13, 1281–1282 (2007).

    CAS  PubMed  Google Scholar 

  75. Takaki, A., Kawai, D. & Yamamoto, K. Molecular mechanisms and new treatment strategies for non-alcoholic steatohepatitis (NASH). Int 15, 7352–7379 (2014).

    Google Scholar 

  76. Tyrer, P. C., Bean, E. G., Ruth Foxwell, A. & Pavli, P. Effects of bacterial products on enterocyte–macrophage interactions in vitro. Biochem. Biophys. Res. Commun. 413, 336–341 (2011).

    CAS  PubMed  Google Scholar 

  77. Baldwin, A. S. Jr. The NF-κB and IκB proteins: new discoveries and insights. Annu. Rev. Immunol. 14, 649–681 (1996).

    CAS  PubMed  Google Scholar 

  78. Everard, A. et al. Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status. Nat. Commun. 5, 5648 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Dixon, L. J., Flask, C. A., Papouchado, B. G., Feldstein, A. E. & Nagy, L. E. Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis. PLoS ONE 8, e56100 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Friedman, S. L. Liver fibrosis in 2012: convergent pathways that cause hepatic fibrosis in NASH. Nat. Rev. Gastroenterol. Hepatol. 10, 71–72 (2013).

    CAS  PubMed  Google Scholar 

  81. Wree, A. et al. NLRP3 inflammasome activation is required for fibrosis development in NAFLD. J. Mol. Med. 92, 1069–1082 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Henao-Mejia, J. et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482, 179–185 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Vijay-Kumar, M. & Gewirtz, Andrew, T. Is predisposition to NAFLD and obesity communicable? Cell Metab. 15, 419–420 (2012).

    CAS  PubMed  Google Scholar 

  84. Wang, L. et al. Methods to determine intestinal permeability and bacterial translocation during liver disease. J. Immunol. Methods 421, 44–53 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Miki, K., Butler, R., Moore, D. & Davidson, G. Rapid and simultaneous quantification of rhamnose, mannitol, and lactulose in urine by HPLC for estimating intestinal permeability in pediatric practice. Clin. Chem. 42, 71–75 (1996).

    CAS  PubMed  Google Scholar 

  86. van Wijck, K. et al. Novel multi-sugar assay for site-specific gastrointestinal permeability analysis: a randomized controlled crossover trial. Clin. Nutr. 32, 245–251 (2013).

    CAS  PubMed  Google Scholar 

  87. Miele, L. et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 49, 1877–1887 (2009).

    CAS  PubMed  Google Scholar 

  88. Arasaradnam, R. P. et al. Evaluation of gut bacterial populations using an electronic e-nose and field asymmetric ion mobility spectrometry: further insights into 'fermentonomics'. J. Med. Eng. Technol. 36, 333–337 (2012).

    CAS  PubMed  Google Scholar 

  89. Verdam, F. J., Rensen, S. S., Driessen, A., Greve, J. W. & Buurman, W. A. Novel evidence for chronic exposure to endotoxin in human nonalcoholic steatohepatitis. J. Clin. Gastroenterol. 45, 149–152 (2011).

    CAS  PubMed  Google Scholar 

  90. Tarantino, G., Scalera, A. & Finelli, C. Liver–spleen axis: intersection between immunity, infections and metabolism. World J. Gastroenterol. 19, 3534–3542 (2013).

    PubMed  PubMed Central  Google Scholar 

  91. Duman, D. G. et al. Colloid scintigraphy in non-alcoholic steatohepatitis: a conventional diagnostic method for an emerging disease. Nucl. Med. Commun. 27, 387–393 (2006).

    PubMed  Google Scholar 

  92. Rosser, E. C. et al. Regulatory B cells are induced by gut microbiota-driven interleukin-1β and interleukin-6 production. Nat. Med. 20, 1334–1339 (2014).

    CAS  PubMed  Google Scholar 

  93. Yuan, J. et al. Endotoxemia unrequired in the pathogenesis of pediatric nonalcoholic steatohepatitis. J. Gastroenterol. Hepatol. 29, 1292–1298 (2014).

    CAS  PubMed  Google Scholar 

  94. Thuy, S. et al. Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. J. Nutr. 138, 1452–1455 (2008).

    CAS  PubMed  Google Scholar 

  95. Guerra Ruiz, A. et al. Lipopolysaccharide-binding protein plasma levels and liver TNF-alpha gene expression in obese patients: evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis. Obes. Surg. 17, 1374–1380 (2007).

    Google Scholar 

  96. Rivera, L. R. et al. Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high-fat diet. Neurogastroenterol. Motil. 26, 1188–1199 (2014).

    CAS  PubMed  Google Scholar 

  97. Jalanka-Tuovinen, J. et al. Faecal microbiota composition and host–microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome. Gut 63, 1737–1745 (2014).

    PubMed  Google Scholar 

  98. Dawes, E. & Foster, S. M. The formation of ethanol in Escherichia coli. Biochim. Biophys. Acta 22, 253–265 (1956).

    CAS  PubMed  Google Scholar 

  99. Cope, K., Risby, T. & Diehl, A. M. Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis. Gastroenterology 119, 1340–1347 (2000).

    CAS  PubMed  Google Scholar 

  100. Nair, S., Cope, K., Terence, R. H. & Diehl, A. M. Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis. Am. J. Gastroenterol. 96, 1200–1204 (2001).

    CAS  PubMed  Google Scholar 

  101. Baker, S. S., Baker, R. D., Liu, W., Nowak, N. J. & Zhu, L. Role of alcohol metabolism in non-alcoholic steatohepatitis. PLoS ONE 5, e9570 (2010).

    PubMed  PubMed Central  Google Scholar 

  102. Parlesak, A., Schäfer, C., Schütz, T., Bode, J. C. & Bode, C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J. Hepatol. 32, 742–747 (2000).

    CAS  PubMed  Google Scholar 

  103. Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57–63 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Spencer, M. D. et al. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology 140, 976–986 (2011).

    CAS  PubMed  Google Scholar 

  105. Dumas, M.-E. et al. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc. Natl Acad. Sci. USA 103, 12511–12516 (2006).

    CAS  PubMed  Google Scholar 

  106. Savard, C. et al. Synergistic interaction of dietary cholesterol and dietary fat in inducing experimental steatohepatitis. Hepatology 57, 81–92 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. de Wit, N. et al. Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine. Am. J. Gastrointest. Liver Physiol. 303, G589–G599 (2012).

    CAS  Google Scholar 

  108. Caesar, R., Tremaroli, V., Kovatcheva-Datchary, P., Cani, Patrice, D. & Bäckhed, F. Crosstalk between gut microbiota and dietary lipids aggravates WAT Inflammation through TLR signaling. Cell Metab. 22, 658–668 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Jakobsdottir, G., Xu, J., Molin, G., Ahrne, S. & Nyman, M. High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects. PLoS ONE 8, e80476 (2013).

    PubMed  PubMed Central  Google Scholar 

  110. Jin, C. J., Sellmann, C., Engstler, A. J., Ziegenhardt, D. & Bergheim, I. Supplementation of sodium butyrate protects mice from the development of non-alcoholic steatohepatitis (NASH). Br. J. Nutr. 114, 1745–1755 (2015).

    CAS  PubMed  Google Scholar 

  111. Wagnerberger, S. et al. Toll-like receptors 1–9 are elevated in livers with fructose-induced hepatic steatosis. Br. J. Nutr. 107, 1727–1738 (2012).

    CAS  PubMed  Google Scholar 

  112. Ishimoto, T. et al. High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase. Hepatology 58, 1632–1643 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Donnelly, K. L. et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J. Clin. Invest. 115, 1343–1351 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Lambert, J. E., Ramos–Roman, M. A., Browning, J. D. & Parks, E. J. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology 146, 726–735 (2014).

    CAS  PubMed  Google Scholar 

  115. Stanhope, K. L. et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J. Clin. Invest. 119, 1322–1334 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Timlin, M. T. & Parks, E. J. Temporal pattern of de novo lipogenesis in the postprandial state in healthy men. Am. J. Clin. Nutr. 81, 35–42 (2005).

    CAS  PubMed  Google Scholar 

  117. Softic, S., Cohen, D. E. & Kahn, C. R. Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig. Dis. Sci. 61, 1282–1293 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Ma, J. et al. Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts. J. Hepatol. 63, 462–469 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Chiavaroli, L., Ha, V., de Souza, R. J., Kendall, C. W. & Sievenpiper, J. L. Overstated associations between fructose and nonalcoholic fatty liver disease. J. Pediatr. Gastroenterol. Nutr. 60, e35 (2015).

    PubMed  Google Scholar 

  120. Abdelmalek, M. F. & Day, C. Sugar sweetened beverages and fatty liver disease: rising concern and call to action. J. Hepatol. 63, 306–308 (2015).

    PubMed  Google Scholar 

  121. Yap, Y. T. et al. Advanced glycation end products as environmental risk factors for the development of type 1 diabetes. Curr. Drug Targets 13, 526–540 (2012).

    CAS  PubMed  Google Scholar 

  122. Rojas, A. et al. Evidence of involvement of the receptor for advanced glycation end-products (RAGE) in the adhesion of Helicobacter pylori to gastric epithelial cells. Microbes Infect. 13, 818–823 (2011).

    CAS  PubMed  Google Scholar 

  123. Däbritz, J. et al. The functional −374T/A polymorphism of the receptor for advanced glycation end products may modulate Crohn's disease. Am. J. Physiol. Gastrointest. Liver Physiol. 300, G823–G832 (2011).

    PubMed  Google Scholar 

  124. Ciccocioppo, R. et al. Role of the advanced glycation end products receptor in Crohn's disease inflammation. World J. Gastroenterol. 19, 8269–8281 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Leung, C. et al. Dietary glycotoxins exacerbate progression of experimental fatty liver disease. J. Hepatol. 60, 832–838 (2014).

    CAS  PubMed  Google Scholar 

  126. Suez, J. et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181–186 (2014).

    CAS  PubMed  Google Scholar 

  127. Payne, A. N., Chassard, C. & Lacroix, C. Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host–microbe interactions contributing to obesity. Obes. Rev. 13, 799–809 (2012).

    CAS  PubMed  Google Scholar 

  128. Swithers, S. E. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol. Metab. 24, 431–441 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. AlKhater, S. A. Paediatric non-alcoholic fatty liver disease: an overview. Obes. Rev. 16, 393–405 (2015).

    CAS  PubMed  Google Scholar 

  130. Bergheim, I. et al. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J. Hepatol. 48, 983–992 (2008).

    CAS  PubMed  Google Scholar 

  131. Trocho, C. et al. Formaldehyde derived from dietary aspartame binds to tissue components in vivo. Life Sci. 63, 337–349 (1998).

    CAS  PubMed  Google Scholar 

  132. Imaizumi, K., Nakatsu, Y., Sato, M., Sedarnawati, Y. & Sugano, M. Effects of xylooligosaccharides on blood glucose, serum and liver lipids and cecum short-chain fatty acids in diabetic rats. Agric. Biol. Chem. 55, 199–205 (1991).

    CAS  Google Scholar 

  133. Hashemi Kani, A., Alavian, S. M., Haghighatdoost, F. & Azadbakht, L. Diet macronutrients composition in nonalcoholic fatty liver disease: a review on the related documents. Hepat. Mon. 14, e10939 (2014).

    PubMed  PubMed Central  Google Scholar 

  134. Seo, D.-B. et al. Fermented green tea extract alleviates obesity and related complications and alters gut microbiota composition in diet-induced obese mice. J. Med. Food 18, 549–556 (2015).

    PubMed  Google Scholar 

  135. Zhou, J. et al. Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, stimulates hepatic autophagy and lipid clearance. PLoS ONE 9, e87161 (2014).

    PubMed  PubMed Central  Google Scholar 

  136. Santamarina, A. B. et al. Decaffeinated green tea extract rich in epigallocatechin-3-gallate prevents fatty liver disease by increased activities of mitochondrial respiratory chain complexes in diet-induced obesity mice. J. Nutr. Biochem. 26, 1348–1356 (2015).

    CAS  PubMed  Google Scholar 

  137. Imatoh, T., Kamimura, S. & Miyazaki, M. Coffee but not green tea consumption is associated with prevalence and severity of hepatic steatosis: the impact on leptin level. Eur. J. Clin. Nutr. 69, 1023–1027 (2015).

    CAS  PubMed  Google Scholar 

  138. Pezeshki, A., Safi, S., Feizi, A., Askari, G. & Karami, F. The effect of green tea extract supplementation on liver enzymes in patients with nonalcoholic fatty liver disease. Int. J. Prev. Med. 6, 131 (2015).

    Google Scholar 

  139. Molloy, J. W. et al. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology 55, 429–436 (2012).

    CAS  PubMed  Google Scholar 

  140. Vitaglione, P. et al. Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins. Hepatology 52, 1652–1661 (2010).

    CAS  PubMed  Google Scholar 

  141. Shen, L. Letter: gut microbiota modulation contributes to coffee's benefits for non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 39, 1441–1442 (2014).

    CAS  PubMed  Google Scholar 

  142. Nakayama, T. & Oishi, K. Influence of coffee (Coffea arabica) and galacto-oligosaccharide consumption on intestinal microbiota and the host responses. FEMS Microbiol. Lett. 343, 161–168 (2013).

    CAS  PubMed  Google Scholar 

  143. Cowan, T. E. et al. Chronic coffee consumption in the diet-induced obese rat: impact on gut microbiota and serum metabolomics. J. Nutr. Biochem. 25, 489–495 (2014).

    CAS  PubMed  Google Scholar 

  144. Dong, H., Lu, F.-e. & Zhao, L. Chinese herbal medicine in the treatment of nonalcoholic fatty liver disease. Chin. J. Integr. Med. 18, 152–160 (2012).

    PubMed  Google Scholar 

  145. Yin, X. et al. Structural changes of gut microbiota in a rat non-alcoholic fatty liver disease model treated with a Chinese herbal formula. Syst. Appl. Microbiol. 36, 188–196 (2013).

    PubMed  Google Scholar 

  146. Yi, C., Leiming, X. & Qin, P. Modulation of gut microbiota with berberine improves nonalcoholic steatohepatitis in mice. J. Clin. Hepatol. 2, 015 (2013).

    Google Scholar 

  147. Spiegel, K., Tasali, E., Leproult, R. & Van Cauter, E. Effects of poor and short sleep on glucose metabolism and obesity risk. Nat. Rev. Endocrinol. 5, 253–261 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Nedeltcheva, A. V., Kilkus, J. M., Imperial, J., Schoeller, D. A. & Penev, P. D. Insufficient sleep undermines dietary efforts to reduce adiposity. Ann. Intern. Med. 153, 435–441 (2010).

    PubMed  PubMed Central  Google Scholar 

  149. Voigt, R. M. et al. Circadian disorganization alters intestinal microbiota. PLoS ONE 9, e97500 (2014).

    PubMed  PubMed Central  Google Scholar 

  150. Summa, K. C. et al. Disruption of the circadian clock in mice increases intestinal permeability and promotes alcohol-induced hepatic pathology and inflammation. PLoS ONE 8, e67102 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Dvornyk, V., Vinogradova, O. & Nevo, E. Origin and evolution of circadian clock genes in prokaryotes. Proc. Natl Acad. Sci. USA 100, 2495–2500 (2003).

    CAS  PubMed  Google Scholar 

  152. Musso, G. et al. Association of obstructive sleep apnoea with the presence and severity of non-alcoholic fatty liver disease. A systematic review and meta-analysis. Obes. Rev. 14, 417–431 (2013).

    CAS  PubMed  Google Scholar 

  153. Mishra, P. et al. Apnoeic–hypopnoeic episodes during obstructive sleep apnoea are associated with histological nonalcoholic steatohepatitis. Liver Int. 28, 1080–1086 (2008).

    CAS  PubMed  Google Scholar 

  154. Zamora-Valdés, D. & Méndez-Sánchez, N. Experimental evidence of obstructive sleep apnea syndrome as a second hit accomplice in nonalcoholic steatohepatitis pathogenesis. Ann. Hepatol. 6, 281–283 (2007).

    PubMed  Google Scholar 

  155. Moreno-Indias, I. et al. Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur. Respir. J. 45, 1055–1065 (2015).

    PubMed  Google Scholar 

  156. Finelli, C. & Tarantino, G. Is there any consensus as to what diet or lifestyle approach is the right one for NAFLD patients. J. Gastrointest. Liver Dis. 21, 293–302 (2012).

    Google Scholar 

  157. Targher, G. & Arcaro, G. Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 191, 235–240 (2007).

    CAS  PubMed  Google Scholar 

  158. Conn, V. S., Hafdahl, A. R., Cooper, P. S., Brown, L. M. & Lusk, S. L. Meta-analysis of workplace physical activity interventions. Am. J. Prev. Med. 37, 330–339 (2009).

    PubMed  PubMed Central  Google Scholar 

  159. Evans, C. C. et al. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PLoS ONE 9, e92193 (2014).

    PubMed  PubMed Central  Google Scholar 

  160. Matsumoto, M. et al. Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum. Biosci. Biotechnol. Biochem. 72, 572–576 (2008).

    CAS  PubMed  Google Scholar 

  161. Clarke, S. F. et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 63, 1913–1920 (2014).

    CAS  PubMed  Google Scholar 

  162. Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl Acad. Sci. USA 110, 9066–9071 (2013).

    CAS  PubMed  Google Scholar 

  163. Murase, T., Haramizu, S., Shimotoyodome, A., Tokimitsu, I. & Hase, T. Green tea extract improves running endurance in mice by stimulating lipid utilization during exercise. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R1550–R1556 (2006).

    CAS  PubMed  Google Scholar 

  164. Patel, R. & DuPont, H. L. New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Clin. Infect. Dis. 60, S108–S121 (2015).

    PubMed  PubMed Central  Google Scholar 

  165. Ferolla, S. M., Armiliato, G. N. d. A., Couto, C. A. & Ferrari, T. C. A. Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease. World J. Hepatol. 7, 559–565 (2015).

    PubMed  PubMed Central  Google Scholar 

  166. Alisi, A. et al. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment. Pharmacol. Ther. 39, 1276–1285 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Lee, J., Hong, S. W., Rhee, E. J. & Lee, W. Y. GLP-1 receptor agonist and non-alcoholic fatty liver disease. Diabetes Metab. J. 36, 262–267 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Campbell, J. E. & Drucker, D. J. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 17, 819–837 (2013).

    CAS  PubMed  Google Scholar 

  169. Malaguarnera, M. et al. Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig. Dis. Sci. 57, 545–553 (2012).

    PubMed  Google Scholar 

  170. Wong, V. et al. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann. Hepatol. 12, 256–262 (2013).

    CAS  PubMed  Google Scholar 

  171. Beserra, B. T. et al. A systematic review and meta-analysis of the prebiotics and synbiotics effects on glycaemia, insulin concentrations and lipid parameters in adult patients with overweight or obesity. Clin. Nutr. 34, 845–858 (2015).

    CAS  PubMed  Google Scholar 

  172. Beserra, B. T. S. et al. A systematic review and meta-analysis of the prebiotics and synbiotics effects on glycaemia, insulin concentrations and lipid parameters in adult patients with overweight or obesity. Clin. Nutr. 34, 845–858 (2015).

    CAS  PubMed  Google Scholar 

  173. Tarantino, G. & Finelli, C. Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease. Future Microbiol. 10, 889–902 (2015).

    CAS  PubMed  Google Scholar 

  174. Miloh, T. Probiotics in pediatric liver disease. J. Clin. Gastroenterol. 49, S33–S36 (2015).

    CAS  PubMed  Google Scholar 

  175. Anand, G., Zarrinpar, A. & Loomba, R. in Seminars in Liver Disease 37–47 (Thieme Medical Publishers, 2016).

    Google Scholar 

  176. Frei, R., Akdis, M. & O'Mahony, L. Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence. Curr. Opin. Gastroenterol. 31, 153–158 (2015).

    CAS  PubMed  Google Scholar 

  177. Younossi, Z., Reyes, M., 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. 39, 3–14 (2014).

    CAS  PubMed  Google Scholar 

  178. Mudaliar, S. et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 145, 574–582.e1 (2013).

    CAS  PubMed  Google Scholar 

  179. Safadi, R. et al. The fatty acid–bile acid conjugate aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 12, 2085–2091.e1 (2014).

    CAS  PubMed  Google Scholar 

  180. Marra, F. & Tacke, F. Roles for chemokines in liver disease. Gastroenterology 147, 577–594.e571 (2014).

    CAS  PubMed  Google Scholar 

  181. Ratziu, V. Pharmacological agents for NASH. Nat. Rev. Gastroenterol. Hepatol. 10, 676–685 (2013).

    CAS  PubMed  Google Scholar 

  182. Gastaldelli, A. & Marchesini, G. Time for Glucagon like peptide-1 receptor agonists treatment for patients with NAFLD? J. Hepatol. 64, 262–264 (2016).

    PubMed  Google Scholar 

  183. Staels, B. et al. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology 58, 1941–1952 (2013).

    CAS  PubMed  Google Scholar 

  184. Cho, I. & Blaser, M. J. The human microbiome: at the interface of health and disease. Nat. Rev. Genet. 13, 260–270 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    PubMed  PubMed Central  Google Scholar 

  186. Mutlu, E. et al. Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol. Clin. Exp. Res. 33, 1836–1846 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. DuPont, A. W. & DuPont, H. L. The intestinal microbiota and chronic disorders of the gut. Nat. Rev. Gastroenterol. Hepatol. 8, 523–531 (2011).

    PubMed  Google Scholar 

  188. Reyes, A. et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466, 334–338 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  189. Norman, J. M., Handley, S. A. & Virgin, H. W. Kingdom-agnostic metagenomics and the importance of complete characterization of enteric microbial communities. Gastroenterology 146, 1459–1469 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  190. Fernández, L. et al. The human milk microbiota: origin and potential roles in health and disease. Pharmacol. Res. 69, 1–10 (2013).

    PubMed  Google Scholar 

  191. De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010).

    PubMed  Google Scholar 

  192. Grzeskowiak, L. et al. Distinct gut microbiota in southeastern African and northern European infants. J. Pediatr. Gastroenterol. Nutr. 54, 812–816 (2012).

    PubMed  Google Scholar 

  193. Sinkiewicz, G. & Nordstrom, E. A. 353 occurrence of Lactobacillus Reuteri, Lactobacilli and Bifidobacteria in human breast milk. Pediatr. Res. 58, 415–415 (2005).

    Google Scholar 

  194. Nobili, V. et al. A protective effect of breastfeeding on the progression of non-alcoholic fatty liver disease. Arch. Dis. Child. 94, 801–805 (2009).

    CAS  PubMed  Google Scholar 

  195. Oben, J. A. et al. Maternal obesity during pregnancy and lactation programs the development of offspring non-alcoholic fatty liver disease in mice. J. Hepatol. 52, 913–920 (2010).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

C.L. is supported by funding from the Department of Health, National Health and Medical Research Council (NHMRC) – 629025, 1029990. P.W.A. is supported by funding from the Department of Health, National Health and Medical Research Council (NHMRC) – 1029990.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to researching data, discussing, writing and reviewing/editing the manuscript.

Corresponding author

Correspondence to Christopher Leung.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leung, C., Rivera, L., Furness, J. et al. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol 13, 412–425 (2016). https://doi.org/10.1038/nrgastro.2016.85

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2016.85

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing