Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota

  • Ruiting Han
  • Junli Ma
  • Houkai Li


Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical “Two-hit” theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a “metabolic organ” that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.


gut microbiota NAFLD obesity insulin resistance bile acids probiotic 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



Houkai Li was funded by National Natural Science Foundation of China (No. 81673662), The Program for Professor of Special Appointment (Eastern Scholar), and Shuguang Scholar (No. 16SG36) at Shanghai Institutions of Higher Learning from Shanghai Municipal Education Commission.


  1. 1.
    Martinez KB, Leone V, Chang EB. Microbial metabolites in health and disease: navigating the unknown in search of function. J Biol Chem 2017; 292(21): 8553–8559PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol 2014; 28(8): 1221–1238PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz–Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Doré J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464(7285): 59–65PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Claesson MJ, Cusack S, O’Sullivan O, Greene–Diniz R, de Weerd H, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, Stanton C, van Sinderen D, O’Connor M, Harnedy N, O’Connor K, Henry C, O’Mahony D, Fitzgerald AP, Shanahan F, Twomey C, Hill C, Ross RP, O’Toole PW. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA 2011; 108(Suppl 1): 4586–4591PubMedCrossRefGoogle Scholar
  5. 5.
    He X, Ji G, Jia W, Li H. Gut microbiota and nonalcoholic fatty liver disease: insights on mechanism and application of metabolomics. Int J Mol Sci 2016; 17(3): 300PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Bordalo Tonucci L, Dos Santos KM, De Luces Fortes Ferreira CL, Ribeiro SM, De Oliveira LL, Martino HS. Gut microbiota and probiotics: focus on diabetes mellitus. Crit Rev Food Sci Nutr 2017; 57(11): 2296–2309PubMedCrossRefGoogle Scholar
  7. 7.
    Kvit KB, Kharchenko NV. Gut microbiota changes as a risk factor for obesity. Wiad Lek 2017; 70(2): 231–235PubMedGoogle Scholar
  8. 8.
    Valsecchi C, Carlotta Tagliacarne S, Castellazzi A. Gut microbiota and obesity. J Clin Gastroenterol 2016; 50(Suppl 2): S157–S158Google Scholar
  9. 9.
    Sanduzzi Zamparelli M, Compare D, Coccoli P, Rocco A, Nardone OM, Marrone G, Gasbarrini A, Grieco A, Nardone G, Miele L. The metabolic role of gut microbiota in the development of nonalcoholic fatty liver disease and cardiovascular disease. Int J Mol Sci 2016; 17(8): E1225Google Scholar
  10. 10.
    Lambert JE, Parnell JA, Eksteen B, Raman M, Bomhof MR, Rioux KP, Madsen KL, Reimer RA. Gut microbiota manipulation with prebiotics in patients with non–alcoholic fatty liver disease: a randomized controlled trial protocol. BMC Gastroenterol 2015; 15 (1): 169Google Scholar
  11. 11.
    Mahana D, Trent CM, Kurtz ZD, Bokulich NA, Battaglia T, Chung J, Müller CL, Li H, Bonneau RA, Blaser MJ. Antibiotic perturbation of the murine gut microbiome enhances the adiposity, insulin resistance, and liver disease associated with high–fat diet. Genome Med 2016; 8(1): 48PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Sze MA, Schloss PD. Looking for a signal in the noise: revisiting obesity and the microbiome. MBio 2016; 7(4): e01018–16Google Scholar
  13. 13.
    Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 2013; 10(11): 686–690PubMedCrossRefGoogle Scholar
  14. 14.
    Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein AE. From NAFLD to NASH to cirrhosis—new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol 2013; 10(11): 627–636PubMedCrossRefGoogle Scholar
  15. 15.
    Liu W, Baker RD, Bhatia T, Zhu L, Baker SS. Pathogenesis of nonalcoholic steatohepatitis. Cell Mol Life Sci 2016; 73(10): 1969–1987PubMedCrossRefGoogle Scholar
  16. 16.
    Hoefert B. Über die bakterienbefunde im duodenalsaft von gesunden und kranken. Zschr Klin Med 1921; 92: 221–235 (in German)Google Scholar
  17. 17.
    Dumas ME, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, Fearnside J, Tatoud R, Blanc V, Lindon JC, Mitchell SC, Holmes E, McCarthy MI, Scott J, Gauguier D, Nicholson JK. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin–resistant mice. Proc Natl Acad Sci USA 2006; 103(33): 12511–12516PubMedCrossRefGoogle Scholar
  18. 18.
    Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998; 114(4): 842–845PubMedCrossRefGoogle Scholar
  19. 19.
    Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444 (7122): 1022–1023PubMedCrossRefGoogle Scholar
  20. 20.
    Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des 2009; 15(13): 1546–1558PubMedCrossRefGoogle Scholar
  21. 21.
    Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, Tang A, Zhong S, Li X, Chen W, Xu R, Wang M, Feng Q, Gong M, Yu J, Zhang Y, Zhang M, Hansen T, Sanchez G, Raes J, Falony G, Okuda S, Almeida M, LeChatelier E, Renault P, Pons N, Batto JM, Zhang Z, Chen H, Yang R, Zheng W, Li S, Yang H, Wang J, Ehrlich SD, Nielsen R, Pedersen O, Kristiansen K, Wang J. A metagenome–wide association study of gut microbiota in type 2 diabetes. Nature 2012; 490(7418): 55–60PubMedCrossRefGoogle Scholar
  22. 22.
    Delzenne NM, Cani PD, Everard A, Neyrinck AM, Bindels LB. Gut microorganisms as promising targets for the management of type 2 diabetes. Diabetologia 2015; 58(10): 2206–2217PubMedCrossRefGoogle Scholar
  23. 23.
    Escobedo G, López–Ortiz E, Torres–Castro I. Gut microbiota as a key player in triggering obesity, systemic inflammation and insulin resistance. Rev Invest Clin 2014; 66(5): 450–459PubMedGoogle Scholar
  24. 24.
    Mehal WZ. The Gordian Knot of dysbiosis, obesity and NAFLD. Nat Rev Gastroenterol Hepatol 2013; 10(11): 637–644PubMedCrossRefGoogle Scholar
  25. 25.
    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(7384): 179–185PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    DiBaise JK, Zhang H, Crowell MD, Krajmalnik–Brown R, Decker GA, Rittmann BE. Gut microbiota and its possible relationship with obesity. Mayo Clin Proc 2008; 83(4): 460–469PubMedCrossRefGoogle Scholar
  27. 27.
    Wieland A, Frank DN, Harnke B, Bambha K. Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease. Aliment Pharmacol Ther 2015; 42(9): 1051–1063PubMedCrossRefGoogle Scholar
  28. 28.
    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(7228): 480–484PubMedCrossRefGoogle Scholar
  29. 29.
    Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 2004; 101(44): 15718–15723PubMedCrossRefGoogle Scholar
  30. 30.
    Dutton S, Trayhurn P. Regulation of angiopoietin–like protein 4/fasting–induced adipose factor (Angptl4/FIAF) expression in mouse white adipose tissue and 3T3–L1 adipocytes. Br J Nutr 2008; 100(1): 18–26PubMedCrossRefGoogle Scholar
  31. 31.
    Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet–induced obesity in germ–free mice. Proc Natl Acad Sci USA 2007; 104(3): 979–984PubMedCrossRefGoogle Scholar
  32. 32.
    Hong YH, Nishimura Y, Hishikawa D, Tsuzuki H, Miyahara H, Gotoh C, Choi KC, Feng DD, Chen C, Lee HG, Katoh K, Roh SG, Sasaki S. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 2005; 146(12): 5092–5099PubMedCrossRefGoogle Scholar
  33. 33.
    Polyzos SA, Kountouras J, Zavos C. Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med 2009; 9(3): 299–314PubMedCrossRefGoogle Scholar
  34. 34.
    Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI. Effects of the gut microbiota on host adiposity are modulated by the short–chain fatty–acid binding G protein–coupled receptor, Gpr41. Proc Natl Acad Sci USA 2008; 105(43): 16767–16772PubMedCrossRefGoogle Scholar
  35. 35.
    Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 2006; 40(3): 235–243PubMedCrossRefGoogle Scholar
  36. 36.
    Kimura I, Inoue D, Maeda T, Hara T, Ichimura A, Miyauchi S, Kobayashi M, Hirasawa A, Tsujimoto G. Short–chain fatty acids and ketones directly regulate sympathetic nervous system via G protein–coupled receptor 41 (GPR41). Proc Natl Acad Sci USA 2011; 108(19): 8030–8035PubMedCrossRefGoogle Scholar
  37. 37.
    Yadav H, Lee JH, Lloyd J, Walter P, Rane SG. Beneficial metabolic effects of a probiotic via butyrate–induced GLP–1 hormone secretion. J Biol Chem 2013; 288(35): 25088–25097PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Leung C, Rivera L, Furness JB, Angus PW. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol 2016; 13 (7): 412–425Google Scholar
  39. 39.
    Kant P, Hull MA. Excess body weight and obesity—the link with gastrointestinal and hepatobiliary cancer. Nat Rev Gastroenterol Hepatol 2011; 8(4): 224–238PubMedCrossRefGoogle Scholar
  40. 40.
    Pagano G, Pacini G, Musso G, Gambino R, Mecca F, Depetris N, Cassader M, David E, Cavallo–Perin P, Rizzetto M. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology 2002; 35(2): 367–372PubMedCrossRefGoogle Scholar
  41. 41.
    Cani PD, Delzenne NM. Gut microflora as a target for energy and metabolic homeostasis. Curr Opin Clin Nutr Metab Care 2007; 10 (6): 729–734PubMedCrossRefGoogle Scholar
  42. 42.
    Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, Petersen KF, Kibbey RG, Goodman AL, Shulman GI. Acetate mediates a microbiome–brain–β–cell axis to promote metabolic syndrome. Nature 2016; 534(7606): 213–217PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Fialho A, Fialho A, Thota P, McCullough AJ, Shen B. Small intestinal bacterial overgrowth is associated with non–alcoholic fatty liver disease. J Gastrointestin Liver Dis 2016; 25(2): 159–165 doi:10.15403/jgld.2014.1121.252.iwgPubMedGoogle Scholar
  44. 44.
    Wu WC, Zhao W, Li S. Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats. World J Gastroenterol 2008; 14(2): 313–317PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Wigg AJ, Roberts–Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor α in the pathogenesis of non–alcoholic steatohepatitis. Gut 2001; 48(2): 206–211PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Saito T, Hayashida H, Furugen R. Comment on: Cani et al. (2007) Metabolic endotoxemia initiates obesity and insulin resistance: Diabetes 56:1761–1772. Diabetes 2007; 56(12): e20 DOI:10.2337/db07–1181Google Scholar
  47. 47.
    Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palù G, Martines D. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2007; 292(2): G518–G525Google Scholar
  48. 48.
    Bluemel S, Williams B, Knight R, Schnabl B. Precision medicine in alcoholic and nonalcoholic fatty liver disease via modulating the gut microbiota. Am J Physiol Gastrointest Liver Physiol 2016; 311 (6): G1018–G1036Google Scholar
  49. 49.
    Kessoku T, Imajo K, Honda Y, Kato T, Ogawa Y, Tomeno W, Higurashi T, Yoneda M, Shimakawa M, Tanaka Y, Kawahara T, Saito S, Haruki U, Wada K, Nakajima A, Tanaka Y. Characteristics of fecal microbiota in Japanese patients with nonalcoholic fatty liver disease: a connection among gut–permeability, endotoxin and NAFLD. Gastroenterology 2017; 152(5): S1200CrossRefGoogle Scholar
  50. 50.
    Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56(7): 1761–1772PubMedCrossRefGoogle Scholar
  51. 51.
    Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver Int 2006; 26(10): 1175–1186PubMedCrossRefGoogle Scholar
  52. 52.
    Stams AJ, Plugge CM. Electron transfer in syntrophic communities of anaerobic bacteria and archaea. Nat Rev Microbiol 2009; 7(8): 568–577PubMedCrossRefGoogle Scholar
  53. 53.
    Kim JJ, Sears DD. TLR4 and Insulin Resistance. Gastroenterol Res Pract 2010; 2010: 212563PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Farrell GC. Signalling links in the liver: knitting SOCS with fat and inflammation. J Hepatol 2005; 43(1): 193–196PubMedCrossRefGoogle Scholar
  55. 55.
    Alisi A, Manco M, Devito R, Piemonte F, Nobili V. Endotoxin and plasminogen activator inhibitor–1 serum levels associated with nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 2010; 50(6): 645–649PubMedCrossRefGoogle Scholar
  56. 56.
    Creely SJ, McTernan PG, Kusminski CM, Fisher M, Da Silva NF, Khanolkar M, Evans M, Harte AL, Kumar S. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab 2007; 292(3): E740–E747PubMedCrossRefGoogle Scholar
  57. 57.
    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(2): 343–350PubMedCrossRefGoogle Scholar
  58. 58.
    Senn JJ, Klover PJ, Nowak IA, Zimmers TA, Koniaris LG, Furlanetto RW, Mooney RA. Suppressor of cytokine signaling–3 (SOCS–3), a potential mediator of interleukin–6–dependent insulin resistance in hepatocytes. J Biol Chem 2003; 278(16): 13740–13746PubMedCrossRefGoogle Scholar
  59. 59.
    Rahman K, Desai C, Iyer SS, Thorn NE, Kumar P, Liu Y, Smith T, Neish AS, Li H, Tan S, Wu P, Liu X, Yu Y, Farris AB, Nusrat A, Parkos CA, Anania FA. Loss of junctional adhesion molecule A promotes severe steatohepatitis in mice on a diet high in saturated fat, fructose, and cholesterol. Gastroenterology 2016; 151(4):733–746PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Corbin KD, Zeisel SH. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr Opin Gastroenterol 2012; 28(2): 159–165PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Zeisel SH. Choline: critical role during fetal development and dietary requirements in adults. Annu Rev Nutr 2006; 26(1): 229–250PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Zeisel SH, Wishnok JS, Blusztajn JK. Formation of methylamines from ingested choline and lecithin. J Pharmacol Exp Ther 1983; 225(2): 320–324PubMedGoogle Scholar
  63. 63.
    al–Waiz M, Mikov M, Mitchell SC, Smith RL. The exogenous origin of trimethylamine in the mouse. Metabolism 1992; 41(2): 135–136PubMedCrossRefGoogle Scholar
  64. 64.
    Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011; 472(7341): 57–63PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Martínez–del Campo A, Bodea S, Hamer HA, Marks JA, Haiser HJ, Turnbaugh PJ, Balskus EP. Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria. MBio 2015; 6(2): e00042–15Google Scholar
  66. 66.
    Sherriff JL, O’Sullivan TA, Properzi C, Oddo JL, Adams LA. Choline, its potential role in nonalcoholic fatty liver disease, and the case for human and bacterial genes. Adv Nutr 2016; 7(1): 5–13PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Spencer MD, Hamp TJ, Reid RW, Fischer LM, Zeisel SH, Fodor AA. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology 2011; 140(3): 976–986PubMedCrossRefGoogle Scholar
  68. 68.
    Betrapally NS, Gillevet PM, Bajaj JS. Changes in the intestinal microbiome and alcoholic and nonalcoholic liver diseases: causes or effects? Gastroenterology 2016; 150(8):1745–1755.e3PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Matsubara T, Li F, Gonzalez FJ. FXR signaling in the enterohepatic system. Mol Cell Endocrinol 2013; 368(1–2): 17–29PubMedCrossRefGoogle Scholar
  70. 70.
    Brighton CA, Rievaj J, Kuhre RE, Glass LL, Schoonjans K, Holst JJ, Gribble FM, Reimann F. Bile acids trigger GLP–1 release predominantly by accessing basolaterally located g proteincoupled bile acid receptors. Endocrinology 2015; 156(11): 3961–3970PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Claudel T, Staels B, Kuipers F. The farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol 2005; 25(10): 2020–2030PubMedCrossRefGoogle Scholar
  72. 72.
    Polyzos SA, Kountouras J, Mantzoros CS. Adipose tissue, obesity and non–alcoholic fatty liver disease. Minerva Endocrinol 2017; 42 (2): 92–108Google Scholar
  73. 73.
    Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J 2006; 25(7): 1419–1425PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Hylemon PB, Zhou H, Pandak WM, Ren S, Gil G, Dent P. Bile acids as regulatory molecules. J Lipid Res 2009; 50(8): 1509–1520PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Kim I, Ahn SH, Inagaki T, Choi M, Ito S, Guo GL, Kliewer SA, Gonzalez FJ. Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J Lipid Res 2007; 48(12): 2664–2672PubMedCrossRefGoogle Scholar
  76. 76.
    Chávez–Talavera O, Tailleux A, Lefebvre P, Staels B. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Gastroenterology 2017; 152(7): 1679–1694PubMedCrossRefGoogle Scholar
  77. 77.
    Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003; 72(1): 137–174PubMedCrossRefGoogle Scholar
  78. 78.
    Stacey M, Webb M. Studies on the antibacterial properties of the bile acids and some compounds derived from cholanic acid. Proc R Soc Med 1947; 134(877): 523–537PubMedCrossRefGoogle Scholar
  79. 79.
    Lorenzo–Zúñiga V, Bartolí R, Planas R, Hofmann AF, Viñado B, Hagey LR, Hernández JM, Mañé J, Alvarez MA, Ausina V, Gassull MA. Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats. Hepatology 2003; 37(3): 551–557PubMedCrossRefGoogle Scholar
  80. 80.
    Ogata Y, Nishi M, Nakayama H, Kuwahara T, Ohnishi Y, Tashiro S. Role of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats. J Surg Res 2003; 115(1): 18–23PubMedCrossRefGoogle Scholar
  81. 81.
    Jamar G, Estadella D, Pisani LP. Contribution of anthocyanin–rich foods in obesity control through gut microbiota interactions. Biofactors 2017; 43(4): 507–516PubMedCrossRefGoogle Scholar
  82. 82.
    Zhu Y, Li F, Guo GL. Tissue–specific function of farnesoid X receptor in liver and intestine. Pharmacol Res 2011; 63(4): 259–265PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Hirokane H, Nakahara M, Tachibana S, Shimizu M, Sato R. Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor–4. J Biol Chem 2004; 279(44): 45685–45692PubMedCrossRefGoogle Scholar
  84. 84.
    Ma J, Zhou Q, Li H. Gut microbiota and nonalcoholic fatty liver disease: insights on mechanisms and therapy. Nutrients 2017; 9(10): 1124PubMedCentralCrossRefGoogle Scholar
  85. 85.
    Yoo JY, Kim SS. Probiotics and prebiotics: present status and future perspectives on metabolic disorders. Nutrients 2016; 8(3): 173PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Sanders ME. Probiotics: definition, sources, selection, and uses. Clin Infect Dis 2008; 46(Suppl 2):S58–61Google Scholar
  87. 87.
    Ferolla SM, Armiliato GN, Couto CA, Ferrari TC. Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease. World J Hepatol 2015; 7(3): 559–565PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Qamar AA. Probiotics in nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and cirrhosis. J Clin Gastroenterol 2015; 49(Suppl 1): S28–S32Google Scholar
  89. 89.
    Fukushima M, Yamada A, Endo T, Nakano M. Effects of a mixture of organisms, Lactobacillus acidophilus or Streptococcus faecalis on δ6–desaturase activity in the livers of rats fed a fat–and cholesterol–enriched diet. Nutrition 1999; 15(5): 373–378PubMedCrossRefGoogle Scholar
  90. 90.
    Nguyen TD, Kang JH, Lee MS. Characterization of Lactobacillus plantarum PH04, a potential probiotic bacterium with cholesterollowering effects. Int J Food Microbiol 2007; 113(3): 358–361PubMedCrossRefGoogle Scholar
  91. 91.
    Okubo H, Sakoda H, Kushiyama A, Fujishiro M, Nakatsu Y, Fukushima T, Matsunaga Y, Kamata H, Asahara T, Yoshida Y, Chonan O, Iwashita M, Nishimura F, Asano T. Lactobacillus casei strain Shirota protects against nonalcoholic steatohepatitis development in a rodent model. Am J Physiol Gastrointest Liver Physiol 2013; 305(12): G911–G918Google Scholar
  92. 92.
    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(3): 531–538PubMedCrossRefGoogle Scholar
  93. 93.
    Kawano M, Miyoshi M, Ogawa A, Sakai F, Kadooka Y. Lactobacillus gasseri SBT2055 inhibits adipose tissue inflammation and intestinal permeability in mice fed a high–fat diet. J Nutr Sci 2016; 5: e23CrossRefGoogle Scholar
  94. 94.
    Fazeli H, Moshtaghian J, Mirlohi M, Shirzadi M. Reduction in serum lipid parameters by incorporation of a native strain of Lactobacillus plantarum A7 in mice. Iranian J Diabetes Lipid Disord 2010; 9: 1–7Google Scholar
  95. 95.
    Wang Y, Xu N, Xi A, Ahmed Z, Zhang B, Bai X. Effects of Lactobacillus plantarum MA2 isolated from Tibet kefir on lipid metabolism and intestinal microflora of rats fed on high–cholesterol diet. Appl Microbiol Biotechnol 2009; 84(2): 341–347PubMedCrossRefGoogle Scholar
  96. 96.
    Li C, Nie SP, Zhu KX, Ding Q, Li C, Xiong T, Xie MY. Lactobacillus plantarum NCU116 improves liver function, oxidative stress and lipid metabolism in rats with high fat diet induced non–alcoholic fatty liver disease. Food Funct 2014; 5(12): 3216–3223PubMedCrossRefGoogle Scholar
  97. 97.
    Aoki R, Kamikado K, Suda W, Takii H, Mikami Y, Suganuma N, Hattori M, Koga Y. A proliferative probiotic Bifidobacterium strain in the gut ameliorates progression of metabolic disorders via microbiota modulation and acetate elevation. Sci Rep 2017; 7: 43522PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Ren T, Huang C, Cheng M. Dietary blueberry and bifidobacteria attenuate nonalcoholic fatty liver disease in rats by affecting SIRT1–mediated signaling pathway. Oxid Med Cell Longev 2014; 2014: 469059PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Plaza–Díaz J, Ruiz–Ojeda FJ, Vilchez–Padial LM, Gil A. Evidence of the anti–inflammatory effects of probiotics and synbiotics in intestinal chronic diseases. Nutrients 2017; 9(6): E555Google Scholar
  100. 100.
    Chen J, Wang R, Li XF, Wang RL. Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome. Br J Nutr 2012; 107(10): 1429–1434PubMedCrossRefGoogle Scholar
  101. 101.
    Cano PG, Santacruz A, Trejo FM, Sanz Y. Bifidobacterium CECT 7765 improves metabolic and immunological alterations associated with obesity in high–fat diet–fed mice. Obesity (Silver Spring) 2013; 21(11): 2310–2321CrossRefGoogle Scholar
  102. 102.
    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(1): 72–77PubMedCrossRefGoogle Scholar
  103. 103.
    Fedorak RN, Feagan BG, Hotte N, Leddin D, Dieleman LA, Petrunia DM, Enns R, Bitton A, Chiba N, Paré P, Rostom A, Marshall J, Depew W, Bernstein CN, Panaccione R, Aumais G, Steinhart AH, Cockeram A, Bailey RJ, Gionchetti P, Wong C, Madsen K. The probiotic VSL#3 has anti–inflammatory effects and could reduce endoscopic recurrence after surgery for Crohn’s disease. Clin Gastroenterol Hepatol 2015; 13(5): 928–935PubMedCrossRefGoogle Scholar
  104. 104.
    Dhiman RK, Rana B, Agrawal S, Garg A, Chopra M, Thumburu KK, Khattri A, Malhotra S, Duseja A, Chawla YK. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology 2014; 147(6): 1327–37PubMedCrossRefGoogle Scholar
  105. 105.
    Wong RK, Yang C, Song GH, Wong J, Ho KY. Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double–blinded placebo study. Dig Dis Sci 2015; 60(1): 186–194PubMedCrossRefGoogle Scholar
  106. 106.
    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(9): e45425Google Scholar
  107. 107.
    Ma X, Hua J, Li Z. Probiotics improve high fat diet–induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J Hepatol 2008; 49(5): 821–830PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Mei L, Tang Y, Li M, Yang P, Liu Z, Yuan J, Zheng P. Coadministration of cholesterol–lowering probiotics and anthraquinone from Cassia obtusifolia L. Ameliorate non–alcoholic fatty liver. PLoS One 2015; 10(9): e0138078Google Scholar
  109. 109.
    Xue L, He J, Gao N, Lu X, Li M, Wu X, Liu Z, Jin Y, Liu J, Xu J, Geng Y. Probiotics may delay the progression of nonalcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia. Sci Rep 2017; 7: 45176PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Kim DH, Kim H, Jeong D, Kang IB, Chon JW, Kim HS, Song KY, Seo KH. Kefir alleviates obesity and hepatic steatosis in high–fat diet–fed mice by modulation of gut microbiota and mycobiota: targeted and untargeted community analysis with correlation of biomarkers. J Nutr Biochem 2017; 44: 35–43PubMedCrossRefGoogle Scholar
  111. 111.
    Karahan N, Işler M, Koyu A, Karahan AG, Başyığıt Kiliç G, Cırış IM, Sütçü R, Onaran I, Cam H, Keskın M. Effects of probiotics on methionine choline deficient diet–induced steatohepatitis in rats. Turk J Gastroenterol 2012; 23(2): 110–121PubMedCrossRefGoogle Scholar
  112. 112.
    Ji YS, Kim HN, Park HJ, Lee JE, Yeo SY, Yang JS, Park SY, Yoon HS, Cho GS, Franz CM, Bomba A, Shin HK, Holzapfel WH. Modulation of the murine microbiome with a concomitant antiobesity effect by Lactobacillus rhamnosus GG and Lactobacillus sakei NR28. Benef Microbes 2012; 3(1): 13–22PubMedCrossRefGoogle Scholar
  113. 113.
    Kobyliak N, Falalyeyeva T, Bodnar P, Beregova T. Probiotics supplemented with omega–3 fatty acids are more effective for hepatic steatosis reduction in an animal model of obesity. Probiotics Antimicrob Proteins 2017; 9(2): 123–130PubMedCrossRefGoogle Scholar
  114. 114.
    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 nonalcoholic steatohepatitis. Aliment Pharmacol Ther 2014; 39(11): 1276–1285PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Famouri F, Shariat Z, Hashemipour M, Keikha M, Kelishadi R. Effects of probiotics on non–alcoholic fatty liver disease in obese children and adolescents: a randomized clinical trial. J Pediatr Gastroenterol Nutr 2017; 64(3):413–417Google Scholar
  116. 116.
    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(6): 740–743PubMedCrossRefGoogle Scholar
  117. 117.
    Roberfroid M. Prebiotics: the concept revisited. J Nutr 2007; 137(3 Suppl 2): 830S–837SGoogle Scholar
  118. 118.
    Parnell JA, Raman M, Rioux KP, Reimer RA. The potential role of prebiotic fibre for treatment and management of non–alcoholic fatty liver disease and associated obesity and insulin resistance. Liver Int 2012; 32(5): 701–711PubMedCrossRefGoogle Scholar
  119. 119.
    Daubioul CA, Horsmans Y, Lambert P, Danse E, Delzenne NM. Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. Eur J Clin Nutr 2005; 59(5): 723–726PubMedCrossRefGoogle Scholar
  120. 120.
    Fan JG, Xu ZJ, Wang GL. Effect of lactulose on establishment of a rat non–alcoholic steatohepatitis model. World J Gastroenterol 2005; 11(32): 5053–5056PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Salminen S, Salminen E. Lactulose, lactic acid bacteria, intestinal microecology and mucosal protection. Scand J Gastroenterol Suppl 1997; 32(sup222): 45–48Google Scholar
  122. 122.
    Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP–2–driven improvement of gut permeability. Gut 2009; 58(8): 1091–1103PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Matsumoto K, Ichimura M, Tsuneyama K, Moritoki Y, Tsunashima H, Omagari K, Hara M, Yasuda I, Miyakawa H, Kikuchi K. Fructo–oligosaccharides and intestinal barrier function in a methionine–choline–deficient mouse model of nonalcoholic steatohepatitis. PLoS One 2017; 12(6): e0175406Google Scholar
  124. 124.
    Neyrinck AM, Possemiers S, Verstraete W, De Backer F, Cani PD, Delzenne NM. Dietary modulation of clostridial cluster XIVa gut bacteria (Roseburia spp.) by chitin–glucan fiber improves host metabolic alterations induced by high–fat diet in mice. J Nutr Biochem 2012; 23(1): 51–59PubMedCrossRefGoogle Scholar
  125. 125.
    Dewulf EM, Cani PD, Claus SP, Fuentes S, Puylaert PG, Neyrinck AM, Bindels LB, de Vos WM, Gibson GR, Thissen JP, Delzenne NM. Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin–type fructans in obese women. Gut 2013; 62(8): 1112–1121PubMedCrossRefGoogle Scholar
  126. 126.
    Micka A, Siepelmeyer A, Holz A, Theis S, Schön C. Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double–blind, placebocontrolled trial. Int J Food Sci Nutr 2017; 68(1): 82–89PubMedCrossRefGoogle Scholar
  127. 127.
    Poesen R, Evenepoel P, de Loor H, Delcour JA, Courtin CM, Kuypers D, Augustijns P, Verbeke K, Meijers B. The influence of prebiotic arabinoxylan oligosaccharides on microbiota derived uremic retention solutes in patients with chronic kidney disease: a randomized controlled trial. PLoS One 2016; 11(4): e0153893PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Tarantino G, Finelli C. Systematic review on intervention with prebiotics/probiotics in patients with obesity–related nonalcoholic fatty liver disease. Future Microbiol 2015; 10(5): 889–902PubMedCrossRefGoogle Scholar
  129. 129.
    de Vrese M, Schrezenmeir J. Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 2008; 111: 1–66PubMedGoogle Scholar
  130. 130.
    Sáez–Lara MJ, Robles–Sanchez C, Ruiz–Ojeda FJ, Plaza–Diaz J, Gil A. 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 2016; 17 (6): E928Google Scholar
  131. 131.
    Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, O’neil DA, Macfarlane GT. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 2005; 54(2): 242–249PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Cortez–Pinto H, Borralho P, Machado J, Lopes MT, Gato IV, Santos AM, Guerreiro AS. Microbiota modulation with synbiotic decreases liver fibrosis in a high fat choline deficient diet mice model of non–alcoholic steatohepatitis (NASH). GE Port J Gastroenterol 2016; 23(3): 132–141PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Mofidi F, Poustchi H, Yari Z, Nourinayyer B, Merat S, Sharafkhah M, Malekzadeh R, Hekmatdoost A. Synbiotic supplementation in lean patients with non–alcoholic fatty liver disease: a pilot, randomised, double–blind, placebo–controlled, clinical trial. Br J Nutr 2017; 117(5): 662–668PubMedCrossRefGoogle Scholar
  134. 134.
    Ferolla SM, Couto CA, Costa–Silva L, Armiliato GN, Pereira CA, Martins FS, Ferrari ML, Vilela EG, Torres HO, Cunha AS, Ferrari TC. Beneficial effect of synbiotic supplementation on hepatic steatosis and anthropometric parameters, but not on gut permeability in a population with nonalcoholic steatohepatitis. Nutrients 2016; 8(7): E397PubMedCrossRefGoogle Scholar
  135. 135.
    Hwang I, Park YJ, Kim YR, Kim YN, Ka S, Lee HY, Seong JK, Seok YJ, Kim JB. Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon–like peptide 1 in diet–induced obesity. FASEB J 2015; 29(6): 2397–2411PubMedCrossRefGoogle Scholar
  136. 136.
    Gangarapu V, Ince AT, Baysal B, Kayar Y, Kılıç U, Gök Ö, Uysal Ö, Şenturk H. Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2015; 27(7): 840–845PubMedCrossRefGoogle Scholar
  137. 137.
    Aroniadis OC, Brandt LJ. Fecal microbiota transplantation: past, present and future. Curr Opin Gastroenterol 2013; 29(1): 79–84PubMedCrossRefGoogle Scholar
  138. 138.
    Cohen NA, Maharshak N. Novel indications for fecal microbial transplantation: update and review of the literature. Dig Dis Sci 2017; 62(5): 1131–1145PubMedCrossRefGoogle Scholar
  139. 139.
    Jegatheesan P, Beutheu S, Ventura G, Sarfati G, Nubret E, Kapel N, Waligora–Dupriet AJ, Bergheim I, Cynober L, De–Bandt JP. Effect of specific amino acids on hepatic lipid metabolism in fructose–induced non–alcoholic fatty liver disease. Clin Nutr 2016; 35(1): 175–182PubMedCrossRefGoogle Scholar
  140. 140.
    Herman MA, Samuel VT. The sweet path to metabolic demise: fructose and lipid synthesis. Trends Endocrinol Metab 2016; 27(10): 719–730PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Clarke SF, Murphy EF, O’Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O’Reilly M, Jeffery IB, Wood–Martin R, Kerins DM, Quigley E, Ross RP, O’Toole PW, Molloy MG, Falvey E, Shanahan F, Cotter PD. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 2014; 63(12): 1913–1920PubMedCrossRefGoogle Scholar
  142. 142.
    Denou E, Marcinko K, Surette MG, Steinberg GR, Schertzer JD. High–intensity exercise training increases the diversity and metabolic capacity of the mouse distal gut microbiota during diet–induced obesity. Am J Physiol Endocrinol Metab 2016; 310 (11): E982–E993Google Scholar
  143. 143.
    Matsumoto M, Inoue R, Tsukahara T, Ushida K, Chiji H, Matsubara N, Hara H. Voluntary running exercise alters microbiota composition and increases n–butyrate concentration in the rat cecum. Biosci Biotechnol Biochem 2008; 72(2): 572–576PubMedCrossRefGoogle Scholar
  144. 144.
    Hua W, Ding L, Chen Y, Gong B, He J, Xu G. Determination of berberine in human plasma by liquid chromatography–electrospray ionization–mass spectrometry. J Pharm Biomed Anal 2007; 44(4): 931–937PubMedCrossRefGoogle Scholar
  145. 145.
    Zhang X, Zhao Y, Zhang M, Pang X, Xu J, Kang C, Li M, Zhang C, Zhang Z, Zhang Y, Li X, Ning G, Zhao L. Structural changes of gut microbiota during berberine–mediated prevention of obesity and insulin resistance in high–fat diet–fed rats. PLoS One 2012; 7 (8): e42529Google Scholar
  146. 146.
    Li C, He JZ, Zhou XD, Xu X. Berberine regulates type 2 diabetes mellitus related with insulin resistance. China J Chin Materia Medica (Zhongguo Zhongyao Zazhi) 2017; 42: 2254–2260 (in Chinese)Google Scholar
  147. 147.
    Xu JH, Liu XZ, Pan W, Zou DJ. Berberine protects against dietinduced obesity through regulating metabolic endotoxemia and gut hormone levels. Mol Med Rep 2017; 15(5): 2765–2787PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Lin P, Lu J, Wang Y, Gu W, Yu J, Zhao R. Naturally occurring stilbenoid TSG reverses non–alcoholic fatty liver diseases via gutliver axis. PLoS One 2015; 10(10): e0140346PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Hussain A, Yadav MK, Bose S, Wang JH, Lim D, Song YK, Ko SG, Kim H. Daesiho–Tang is an effective herbal formulation in attenuation of obesity in mice through alteration of gene expression and modulation of intestinal microbiota. PLoS One 2016; 11(11): e0165483PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Yin X, Peng J, Zhao L, Yu Y, Zhang X, Liu P, Feng Q, Hu Y, Pang X. Structural changes of gut microbiota in a rat non–alcoholic fatty liver disease model treated with a Chinese herbal formula. Syst Appl Microbiol 2013; 36(3): 188–196PubMedCrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Biomedical ResearchShanghai University of Traditional Chinese MedicineShanghaiChina

Personalised recommendations