Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanisms and Therapy
Abstract
:1. Introduction
2. Roles of the Gut Microbiota in NAFLD Development
3. Gut Microbiota-Targeted Therapies in NAFLD
3.1. Gut Microbiota-Targeted Therapy with Probiotics
3.2. Gut Microbiota-Targeted Therapy with Prebiotic
3.3. Gut Microbiota-Targeted Therapy with Synbiotic
3.4. Gut Microbiota-Targeted Therapies with Other Approaches
4. Conclusions and Perspectives
Acknowledgments
Author Contributions
Conflicts of Interest
Appendix A
- The main source of material was pubmed, and the search keywords used were as follows: “gut microbiota”, “gut flora”, “nonalcoholic fatty liver disease(NAFLD)”, “nonalcoholic steatohepatitis(NASH)”, “steatosis”,“probiotic”, “prebiotic”, “antibiotic”, “herbal medicince”;
- Selected papers have no language restrictions;
- Most of the papers selected were published during the past 10 years;
- References of some identified papers were further searched for related papers to cover this topic as completely as possible.
References
- Minemura, M.; Shimizu, Y. Gut microbiota and liver diseases. World J. Gastroenterol. 2015, 21, 1691–1702. [Google Scholar] [CrossRef] [PubMed]
- Yoo, J.Y.; Kim, S.S. Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders. Nutrients 2016, 8, 173. [Google Scholar] [CrossRef] [PubMed]
- Hooper, L.V.; Wong, M.H.; Thelin, A.; Hansson, L.; Falk, P.G.; Gordon, J.I. Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001, 291, 881–884. [Google Scholar] [CrossRef] [PubMed]
- De La Serre, C.B.; Ellis, C.L.; Lee, J.; Hartman, A.L.; Rutledge, J.C.; Raybould, H.E. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 299, G440–G448. [Google Scholar] [CrossRef] [PubMed]
- Qin, J.; Li, Y.; Cai, Z.; Li, S.; Zhu, J.; Zhang, F.; Liang, S.; Zhang, W.; Guan, Y.; Shen, D.; et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012, 490, 55–60. [Google Scholar] [CrossRef] [PubMed]
- Delzenne, N.M.; Cani, P.D.; Everard, A.; Neyrinck, A.M.; Bindels, L.B. Gut microorganisms as promising targets for the management of type 2 diabetes. Diabetologia 2015, 58, 2206–2217. [Google Scholar] [CrossRef] [PubMed]
- Escobedo, G.; Lopez-Ortiz, E.; Torres-Castro, I. Gut microbiota as a key player in triggering obesity, systemic inflammation and insulin resistance. Rev. Investig. Clin. 2014, 66, 450–459. [Google Scholar]
- Mehal, W.Z. The Gordian Knot of dysbiosis, obesity and NAFLD. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 637–644. [Google Scholar] [CrossRef] [PubMed]
- Henao-Mejia, J.; Elinav, E.; Jin, C.; Hao, L.; Mehal, W.Z.; Strowig, T.; Thaiss, C.A.; Kau, A.L.; Eisenbarth, S.C.; Jurczak, M.J.; et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012, 482, 179–185. [Google Scholar] [CrossRef] [PubMed]
- DiBaise, J.K.; Zhang, H.; Crowell, M.D.; Krajmalnik-Brown, R.; Decker, G.A.; Rittmann, B.E. Gut microbiota and its possible relationship with obesity. Mayo Clin. Proc. 2008, 83, 460–469. [Google Scholar] [CrossRef] [PubMed]
- Chong-Nguyen, C.; Duboc, H.; Sokol, H. The gut microbiota, a new cardiovascular risk factor? Presse Med. 2017, 46, 708–713. [Google Scholar] [CrossRef] [PubMed]
- Kitai, T.; Tang, W.H.W. The Role and Impact of Gut Microbiota in Cardiovascular Disease. Rev. Esp. Cardiol. 2017, 70, 799–800. [Google Scholar] [CrossRef] [PubMed]
- Tang, W.H.; Kitai, T.; Hazen, S.L. Gut Microbiota in Cardiovascular Health and Disease. Circ. Res. 2017, 120, 1183–1196. [Google Scholar] [CrossRef] [PubMed]
- Wieland, A.; Frank, D.N.; Harnke, B.; Bambha, K. Systematic review: Microbial dysbiosis and nonalcoholic fatty liver disease. Aliment. Pharmacol. Ther. 2015, 42, 1051–1063. [Google Scholar] [CrossRef] [PubMed]
- Wree, A.; Broderick, L.; Canbay, A.; Hoffman, H.M.; Feldstein, A.E. From NAFLD to NASH to cirrhosis-new insights into disease mechanisms. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 627–636. [Google Scholar] [CrossRef] [PubMed]
- Day, C.P.; James, O.F. Steatohepatitis: A tale of two “hits”? Gastroenterology 1998, 114, 842–845. [Google Scholar] [CrossRef]
- 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, 300. [Google Scholar] [CrossRef] [PubMed]
- Shen, J.; Obin, M.S.; Zhao, L. The gut microbiota, obesity and insulin resistance. Mol. Asp. Med. 2013, 34, 39–58. [Google Scholar] [CrossRef] [PubMed]
- Mouzaki, M.; Bandsma, R. Targeting the Gut Microbiota for the Treatment of Non-Alcoholic Fatty Liver Disease. Curr. Drug Targets 2015, 16, 1324–1331. [Google Scholar] [CrossRef] [PubMed]
- Kelishadi, R.; Farajian, S.; Mirlohi, M. Probiotics as a novel treatment for non-alcoholic Fatty liver disease; a systematic review on the current evidences. Hepat. Mon. 2013, 13, e7233. [Google Scholar] [CrossRef] [PubMed]
- Ley, R.E.; Turnbaugh, P.J.; Klein, S.; Gordon, J.I. Microbial ecology: Human gut microbes associated with obesity. Nature 2006, 444, 1022–1023. [Google Scholar] [CrossRef] [PubMed]
- Samuel, B.S.; Shaito, A.; Motoike, T.; Rey, F.E.; Backhed, F.; Manchester, J.K.; Hammer, R.E.; Williams, S.C.; Crowley, J.; Yanagisawa, M.; et al. 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, 16767–16772. [Google Scholar] [CrossRef] [PubMed]
- Wong, J.M.; de Souza, R.; Kendall, C.W.; Emam, A.; Jenkins, D.J. Colonic health: Fermentation and short chain fatty acids. J. Clin. Gastroenterol. 2006, 40, 235–243. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Delzenne, N.M. The role of the gut microbiota in energy metabolism and metabolic disease. Curr. Pharm. Des. 2009, 15, 1546–1558. [Google Scholar] [CrossRef] [PubMed]
- Backhed, F.; Ding, H.; Wang, T.; Hooper, L.V.; Koh, G.Y.; Nagy, A.; Semenkovich, C.F.; Gordon, J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 2004, 101, 15718–15723. [Google Scholar] [CrossRef] [PubMed]
- Turnbaugh, P.J.; Ley, R.E.; Mahowald, M.A.; Magrini, V.; Mardis, E.R.; Gordon, J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006, 444, 1027–1031. [Google Scholar] [CrossRef] [PubMed]
- Moschen, A.R.; Kaser, S.; Tilg, H. Non-alcoholic steatohepatitis: A microbiota-driven disease. Trends Endocrinol. Metab. 2013, 24, 537–545. [Google Scholar] [CrossRef] [PubMed]
- 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, 367–372. [Google Scholar] [CrossRef] [PubMed]
- Tarantino, G.; Caputi, A. JNKs, insulin resistance and inflammation: A possible link between NAFLD and coronary artery disease. World J. Gastroenterol. 2011, 17, 3785–3794. [Google Scholar] [CrossRef] [PubMed]
- Farrell, G.C. Signalling links in the liver: Knitting SOCS with fat and inflammation. J. Hepatol. 2005, 43, 193–196. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Amar, J.; Iglesias, M.A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A.M.; Fava, F.; Tuohy, K.M.; Chabo, C.; et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007, 56, 1761–1772. [Google Scholar] [CrossRef] [PubMed]
- Caesar, R.; Reigstad, C.S.; Backhed, H.K.; Reinhardt, C.; Ketonen, M.; Lunden, G.O.; Cani, P.D.; Backhed, F. Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice. Gut 2012, 61, 1701–1707. [Google Scholar] [CrossRef] [PubMed]
- Wellen, K.E.; Hotamisligil, G.S. Inflammation, stress, and diabetes. J. Clin. Investig. 2005, 115, 1111–1119. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Delzenne, N.M. Gut microflora as a target for energy and metabolic homeostasis. Curr. Opin. Clin. Nutr. Metab. Care 2007, 10, 729–734. [Google Scholar] [CrossRef] [PubMed]
- Corbin, K.D.; Zeisel, S.H. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr. Opin. Gastroenterol. 2012, 28, 159–165. [Google Scholar] [CrossRef] [PubMed]
- Zeisel, S.H. Choline: Critical role during fetal development and dietary requirements in adults. Annu. Rev. Nutr. 2006, 26, 229–250. [Google Scholar] [CrossRef] [PubMed]
- 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. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011, 472, 57–63. [Google Scholar] [CrossRef] [PubMed]
- Brown, J.M.; Hazen, S.L. The gut microbial endocrine organ: Bacterially derived signals driving cardiometabolic diseases. Annu. Rev. Med. 2015, 66, 343–359. [Google Scholar] [CrossRef] [PubMed]
- Tang, W.H.; Wang, Z.; Levison, B.S.; Koeth, R.A.; Britt, E.B.; Fu, X.; Wu, Y.; Hazen, S.L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 2013, 368, 1575–1584. [Google Scholar] [CrossRef] [PubMed]
- Spencer, M.D.; Hamp, T.J.; Reid, R.W.; Fischer, L.M.; Zeisel, S.H.; Fodor, A.A. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology 2011, 140, 976–986. [Google Scholar] [CrossRef] [PubMed]
- Lorenzo-Zuniga, V.; Bartoli, R.; Planas, R.; Hofmann, A.F.; Vinado, B.; Hagey, L.R.; Hernandez, J.M.; Mane, J.; Alvarez, M.A.; Ausina, V.; et al. Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats. Hepatology 2003, 37, 551–557. [Google Scholar] [CrossRef] [PubMed]
- 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, 18–23. [Google Scholar] [CrossRef]
- Fuchs, C.; Claudel, T.; Trauner, M. Bile acid-mediated control of liver triglycerides. Semin. Liver Dis. 2013, 33, 330–342. [Google Scholar] [CrossRef] [PubMed]
- Houten, S.M.; Watanabe, M.; Auwerx, J. Endocrine functions of bile acids. EMBO J. 2006, 25, 1419–1425. [Google Scholar] [CrossRef] [PubMed]
- Hylemon, P.B.; Zhou, H.; Pandak, W.M.; Ren, S.; Gil, G.; Dent, P. Bile acids as regulatory molecules. J. Lipid Res. 2009, 50, 1509–1520. [Google Scholar] [CrossRef] [PubMed]
- 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, 2020–2030. [Google Scholar] [CrossRef] [PubMed]
- 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. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J. Clin. Investig. 2015, 125, 386–402. [Google Scholar] [CrossRef] [PubMed]
- Bashiardes, S.; Shapiro, H.; Rozin, S.; Shibolet, O.; Elinav, E. Non-alcoholic fatty liver and the gut microbiota. Mol. Metab. 2016, 5, 782–794. [Google Scholar] [CrossRef] [PubMed]
- Abu-Shanab, A.; Quigley, E.M. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat. Rev. Gastroenterol. Hepatol. 2010, 7, 691–701. [Google Scholar] [CrossRef] [PubMed]
- Kobyliak, N.; Virchenko, O.; Falalyeyeva, T. Pathophysiological role of host microbiota in the development of obesity. Nutr. J. 2016, 15, 43. [Google Scholar] [CrossRef] [PubMed]
- Paolella, G.; Mandato, C.; Pierri, L.; Poeta, M.; Di Stasi, M.; Vajro, P. Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease. World J. Gastroenterol. 2014, 20, 15518–15531. [Google Scholar] [CrossRef] [PubMed]
- Marchesi, J.R.; Adams, D.H.; Fava, F.; Hermes, G.D.; Hirschfield, G.M.; Hold, G.; Quraishi, M.N.; Kinross, J.; Smidt, H.; Tuohy, K.M.; et al. The gut microbiota and host health: A new clinical frontier. Gut 2016, 65, 330–339. [Google Scholar] [CrossRef] [PubMed]
- Kirpich, I.A.; Marsano, L.S.; McClain, C.J. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease. Clin. Biochem. 2015, 48, 923–930. [Google Scholar] [CrossRef] [PubMed]
- Usami, M.; Miyoshi, M.; Yamashita, H. Gut microbiota and host metabolism in liver cirrhosis. World J. Gastroenterol. 2015, 21, 11597–11608. [Google Scholar] [CrossRef] [PubMed]
- Festi, D.; Schiumerini, R.; Eusebi, L.H.; Marasco, G.; Taddia, M.; Colecchia, A. Gut microbiota and metabolic syndrome. World J. Gastroenterol. 2014, 20, 16079–16094. [Google Scholar] [CrossRef] [PubMed]
- Druart, C.; Alligier, M.; Salazar, N.; Neyrinck, A.M.; Delzenne, N.M. Modulation of the gut microbiota by nutrients with prebiotic and probiotic properties. Adv. Nutr. 2014, 5, 624S–633S. [Google Scholar] [CrossRef] [PubMed]
- Finelli, C.; Tarantino, G. Non-alcoholic fatty liver disease, diet and gut microbiota. EXCLI J. 2014, 13, 461–490. [Google Scholar] [PubMed]
- Patel, R.; DuPont, H.L. New approaches for bacteriotherapy: Prebiotics, new-generation probiotics, and synbiotics. Clin. Infect. Dis. 2015, 60 (Suppl. 2), S108–S121. [Google Scholar] [CrossRef] [PubMed]
- Ferolla, S.M.; Armiliato, G.N.; Couto, C.A.; Ferrari, T.C. The role of intestinal bacteria overgrowth in obesity-related nonalcoholic fatty liver disease. Nutrients 2014, 6, 5583–5599. [Google Scholar] [CrossRef] [PubMed]
- Fialho, A.; Thota, P.; McCullough, A.J.; Shen, B. Small Intestinal Bacterial Overgrowth Is Associated with Non-Alcoholic Fatty Liver Disease. J. Gastrointestin. Liver Dis. 2016, 25, 159–165. [Google Scholar] [CrossRef] [PubMed]
- Duvnjak, M.; Tomasic, V.; Gomercic, M.; Smircic Duvnjak, L.; Barsic, N.; Lerotic, I. Therapy of nonalcoholic fatty liver disease: Current status. J. Physiol. Pharmacol. 2009, 60 (Suppl. 7), 57–66. [Google Scholar] [PubMed]
- Sanders, M.E. Probiotics: Definition, sources, selection, and uses. Clin. Infect. Dis. 2008, 46 (Suppl. 2), S58–S61; discussion S144–S151. [Google Scholar] [CrossRef] [PubMed]
- Miura, K.; Ohnishi, H. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease. World J. Gastroenterol. 2014, 20, 7381–7791. [Google Scholar] [CrossRef] [PubMed]
- Okubo, H.; Sakoda, H.; Kushiyama, A.; Fujishiro, M.; Nakatsu, Y.; Fukushima, T.; Matsunaga, Y.; Kamata, H.; Asahara, T.; Yoshida, Y.; et al. Lactobacillus casei strain Shirota protects against nonalcoholic steatohepatitis development in a rodent model. Am. J. Physiol. Gastrointest. Liver Physiol. 2013, 305, G911–G918. [Google Scholar] [CrossRef] [PubMed]
- Naito, E.; Yoshida, Y.; Makino, K.; Kounoshi, Y.; Kunihiro, S.; Takahashi, R.; Matsuzaki, T.; Miyazaki, K.; Ishikawa, F. Beneficial effect of oral administration of Lactobacillus casei strain Shirota on insulin resistance in diet-induced obesity mice. J. Appl. Microbiol. 2011, 110, 650–657. [Google Scholar] [CrossRef] [PubMed]
- Wagnerberger, S.; Spruss, A.; Kanuri, G.; Stahl, C.; Schroder, M.; Vetter, W.; Bischoff, S.C.; Bergheim, I. Lactobacillus casei Shirota protects from fructose-induced liver steatosis: A mouse model. J. Nutr. Biochem. 2013, 24, 531–538. [Google Scholar] [CrossRef] [PubMed]
- Fukushima, M.; Yamada, A.; Endo, T.; Nakano, M. Effects of a mixture of organisms, Lactobacillus acidophilus or Streptococcus faecalis on delta6-desaturase activity in the livers of rats fed a fat- and cholesterol-enriched diet. Nutrition 1999, 15, 373–378. [Google Scholar] [CrossRef]
- Nguyen, T.D.; Kang, J.H.; Lee, M.S. Characterization of Lactobacillus plantarum PH04, a potential probiotic bacterium with cholesterol-lowering effects. Int. J. Food Microbiol. 2007, 113, 358–361. [Google Scholar] [CrossRef] [PubMed]
- Anderson, J.W.; Gilliland, S.E. Effect of fermented milk (yogurt) containing Lactobacillus acidophilus L1 on serum cholesterol in hypercholesterolemic humans. J. Am. Coll. Nutr. 1999, 18, 43–50. [Google Scholar] [CrossRef] [PubMed]
- Sohn, W.; Jun, D.W.; Lee, K.N.; Lee, H.L.; Lee, O.Y.; Choi, H.S.; Yoon, B.C. Lactobacillus paracasei Induces M2-Dominant Kupffer Cell Polarization in a Mouse Model of Nonalcoholic Steatohepatitis. Dig. Dis. Sci. 2015, 60, 3340–3350. [Google Scholar] [CrossRef] [PubMed]
- Ford, A.C.; Quigley, E.M.; Lacy, B.E.; Lembo, A.J.; Saito, Y.A.; Schiller, L.R.; Soffer, E.E.; Spiegel, B.M.; Moayyedi, P. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: Systematic review and meta-analysis. Am. J. Gastroenterol. 2014, 109, 1547–1561; quiz 1546, 1562. [Google Scholar] [CrossRef] [PubMed]
- Ghouri, Y.A.; Richards, D.M.; Rahimi, E.F.; Krill, J.T.; Jelinek, K.A.; DuPont, A.W. Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease. Clin. Exp. Gastroenterol. 2014, 7, 473–487. [Google Scholar] [CrossRef] [PubMed]
- Fazeli, H.; Moshtaghian, J.; Mirlohi, M.; Shirzadi, M. Reduction in serum lipid parameters by incorporation of a native strain of Lactobacillus Plantarum A7 in Mice. Iran. J. Diabetes Lipid Disord. 2010, 9, 1–7. [Google Scholar]
- 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, 341–347. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Nie, S.P.; Zhu, K.X.; Ding, Q.; Xiong, T.; Xie, M.Y. 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, 3216–3223. [Google Scholar] [CrossRef] [PubMed]
- Ritze, Y.; Bardos, G.; Claus, A.; Ehrmann, V.; Bergheim, I.; Schwiertz, A.; Bischoff, S.C. Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice. PLoS ONE 2014, 9, e80169. [Google Scholar] [CrossRef] [PubMed]
- Kim, B.; Park, K.Y.; Ji, Y.; Park, S.; Holzapfel, W.; Hyun, C.K. Protective effects of Lactobacillus rhamnosus GG against dyslipidemia in high-fat diet-induced obese mice. Biochem. Biophys. Res. Commun. 2016, 473, 530–536. [Google Scholar] [CrossRef] [PubMed]
- Xin, J.; Zeng, D.; Wang, H.; Ni, X.; Yi, D.; Pan, K.; Jing, B. Preventing non-alcoholic fatty liver disease through Lactobacillus johnsonii BS15 by attenuating inflammation and mitochondrial injury and improving gut environment in obese mice. Appl. Microbiol. Biotechnol. 2014, 98, 6817–6829. [Google Scholar] [CrossRef] [PubMed]
- Hsieh, F.C.; Lee, C.L.; Chai, C.Y.; Chen, W.T.; Lu, Y.C.; Wu, C.S. Oral administration of Lactobacillus reuteri GMNL-263 improves insulin resistance and ameliorates hepatic steatosis in high fructose-fed rats. Nutr. Metab. (Lond.) 2013, 10, 35. [Google Scholar] [CrossRef] [PubMed]
- Kang, J.H.; Yun, S.I.; Park, M.H.; Park, J.H.; Jeong, S.Y.; Park, H.O. Anti-obesity effect of Lactobacillus gasseri BNR17 in high-sucrose diet-induced obese mice. PLoS ONE 2013, 8, e54617. [Google Scholar] [CrossRef] [PubMed]
- 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, 43522. [Google Scholar] [CrossRef] [PubMed]
- 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, 469059. [Google Scholar] [CrossRef] [PubMed]
- Plaza-Diaz, J.; Ruiz-Ojeda, F.J.; Vilchez-Padial, L.M.; Gil, A. Evidence of the Anti-Inflammatory Effects of Probiotics and Synbiotics in Intestinal Chronic Diseases. Nutrients 2017, 9. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Wang, R.; Li, X.F.; Wang, R.L. Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome. Br. J. Nutr. 2012, 107, 1429–1434. [Google Scholar] [CrossRef] [PubMed]
- Cano, P.G.; Santacruz, A.; Trejo, F.M.; Sanz, Y. Bifidobacterium CECT 7765 improves metabolic and immunological alterations associated with obesity in high-fat diet-fed mice. Obesity 2013, 21, 2310–2321. [Google Scholar] [CrossRef] [PubMed]
- Xu, R.Y.; Wan, Y.P.; Fang, Q.Y.; Lu, W.; Cai, W. Supplementation with probiotics modifies gut flora and attenuates liver fat accumulation in rat nonalcoholic fatty liver disease model. J. Clin. Biochem. Nutr. 2012, 50, 72–77. [Google Scholar] [CrossRef] [PubMed]
- Sinha, A.; Gupta, S.S.; Chellani, H.; Maliye, C.; Kumari, V.; Arya, S.; Garg, B.S.; Gaur, S.D.; Gaind, R.; Deotale, V.; et al. Role of probiotics VSL#3 in prevention of suspected sepsis in low birthweight infants in India: A randomised controlled trial. BMJ Open 2015, 5, e006564. [Google Scholar] [CrossRef] [PubMed]
- Fedorak, R.N.; Feagan, B.G.; Hotte, N.; Leddin, D.; Dieleman, L.A.; Petrunia, D.M.; Enns, R.; Bitton, A.; Chiba, N.; Pare, P.; et al. The probiotic VSL#3 has anti-inflammatory effects and could reduce endoscopic recurrence after surgery for Crohn’s disease. Clin. Gastroenterol. Hepatol. 2015, 13, 928–935. [Google Scholar] [CrossRef] [PubMed]
- Dhiman, R.K.; Rana, B.; Agrawal, S.; Garg, A.; Chopra, M.; Thumburu, K.K.; Khattri, A.; Malhotra, S.; Duseja, A.; Chawla, Y.K. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: A randomized, controlled trial. Gastroenterology 2014, 147, 1327–1337. [Google Scholar] [CrossRef] [PubMed]
- Wong, R.K.; Yang, C.; Song, G.H.; Wong, J.; Ho, K.Y. 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, 186–194. [Google Scholar] [CrossRef] [PubMed]
- Mencarelli, A.; Cipriani, S.; Renga, B.; Bruno, A.; D’Amore, C.; Distrutti, E.; Fiorucci, S. VSL#3 resets insulin signaling and protects against NASH and atherosclerosis in a model of genetic dyslipidemia and intestinal inflammation. PLoS ONE 2012, 7, e45425. [Google Scholar] [CrossRef]
- Esposito, E.; Iacono, A.; Bianco, G.; Autore, G.; Cuzzocrea, S.; Vajro, P.; Canani, R.B.; Calignano, A.; Raso, G.M.; Meli, R. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J. Nutr. 2009, 139, 905–911. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Yang, S.; Lin, H.; Huang, J.; Watkins, P.A.; Moser, A.B.; Desimone, C.; Song, X.Y.; Diehl, A.M. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 2003, 37, 343–350. [Google Scholar] [CrossRef] [PubMed]
- Ma, X.; Hua, J.; Li, Z. Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J. Hepatol. 2008, 49, 821–830. [Google Scholar] [CrossRef] [PubMed]
- Velayudham, A.; Dolganiuc, A.; Ellis, M.; Petrasek, J.; Kodys, K.; Mandrekar, P.; Szabo, G. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology 2009, 49, 989–997. [Google Scholar] [CrossRef] [PubMed]
- Mei, L.; Tang, Y.; Li, M.; Yang, P.; Liu, Z.; Yuan, J.; Zheng, P. Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver. PLoS ONE 2015, 10, e0138078. [Google Scholar] [CrossRef]
- Xue, L.; He, J.; Gao, N.; Lu, X.; Li, M.; Wu, X.; Liu, Z.; Jin, Y.; Liu, J.; Xu, J.; et al. Probiotics may delay the progression of nonalcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia. Sci. Rep. 2017, 7, 45176. [Google Scholar] [CrossRef] [PubMed]
- Kim, D.H.; Kim, H.; Jeong, D.; Kang, I.B.; Chon, J.W.; Kim, H.S.; Song, K.Y.; Seo, K.H. 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, 35–43. [Google Scholar] [CrossRef] [PubMed]
- Karahan, N.; Isler, M.; Koyu, A.; Karahan, A.G.; Basyigit Kilic, G.; Ciris, I.M.; Sutcu, R.; Onaran, I.; Cam, H.; Keskin, M. Effects of probiotics on methionine choline deficient diet-induced steatohepatitis in rats. Turk. J. Gastroenterol. 2012, 23, 110–121. [Google Scholar] [CrossRef] [PubMed]
- Ji, Y.S.; Kim, H.N.; Park, H.J.; Lee, J.E.; Yeo, S.Y.; Yang, J.S.; Park, S.Y.; Yoon, H.S.; Cho, G.S.; Franz, C.M.; et al. Modulation of the murine microbiome with a concomitant anti-obesity effect by Lactobacillus rhamnosus GG and Lactobacillus sakei NR28. Benef. Microbes 2012, 3, 13–22. [Google Scholar] [CrossRef] [PubMed]
- 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, 123–130. [Google Scholar] [CrossRef] [PubMed]
- Seo, M.; Inoue, I.; Tanaka, M.; Matsuda, N.; Nakano, T.; Awata, T.; Katayama, S.; Alpers, D.H.; Komoda, T. Clostridium butyricum MIYAIRI 588 improves high-fat diet-induced non-alcoholic fatty liver disease in rats. Dig. Dis. Sci. 2013, 58, 3534–3544. [Google Scholar] [CrossRef] [PubMed]
- Endo, H.; Niioka, M.; Kobayashi, N.; Tanaka, M.; Watanabe, T. Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: New insight into the probiotics for the gut-liver axis. PLoS ONE 2013, 8, e63388. [Google Scholar] [CrossRef] [PubMed]
- Alisi, A.; Bedogni, G.; Baviera, G.; Giorgio, V.; Porro, E.; Paris, C.; Giammaria, P.; Reali, L.; Anania, F.; Nobili, V. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment. Pharmacol. Ther. 2014, 39, 1276–1285. [Google Scholar] [CrossRef] [PubMed]
- Vajro, P.; Mandato, C.; Licenziati, M.R.; Franzese, A.; Vitale, D.F.; Lenta, S.; Caropreso, M.; Vallone, G.; Meli, R. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J. Pediatr. Gastroenterol. Nutr. 2011, 52, 740–743. [Google Scholar] [CrossRef] [PubMed]
- Aller, R.; De Luis, D.A.; Izaola, O.; Conde, R.; Gonzalez Sagrado, M.; Primo, D.; De La Fuente, B.; Gonzalez, J. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: A double blind randomized clinical trial. Eur. Rev. Med. Pharmacol. Sci. 2011, 15, 1090–1095. [Google Scholar] [PubMed]
- Sepideh, A.; Karim, P.; Hossein, A.; Leila, R.; Hamdollah, M.; Mohammad, E.G.; Mojtaba, S.; Mohammad, S.; Ghader, G.; Seyed Moayed, A. Effects of Multistrain Probiotic Supplementation on Glycemic and Inflammatory Indices in Patients with Nonalcoholic Fatty Liver Disease: A Double-Blind Randomized Clinical Trial. J. Am. Coll. Nutr. 2016, 35, 500–505. [Google Scholar] [CrossRef] [PubMed]
- Shavakhi, A.; Minakari, M.; Firouzian, H.; Assali, R.; Hekmatdoost, A.; Ferns, G. Effect of a Probiotic and Metformin on Liver Aminotransferases in Non-alcoholic Steatohepatitis: A Double Blind Randomized Clinical Trial. Int. J. Prev. Med. 2013, 4, 531–537. [Google Scholar] [PubMed]
- Zvenigorodskaia, L.A.; Cherkashova, E.A.; Samsonova, N.G.; Nilova, T.V.; Sil’verstova, S. Advisability of using probiotics in the treatment of atherogenic dyslipidemia. Eksp. Klin. Gastroenterol. 2011, 2, 37–43. [Google Scholar]
- Solga, S.F.; Buckley, G.; Clark, J.M.; Horska, A.; Diehl, A.M. The effect of a probiotic on hepatic steatosis. J. Clin. Gastroenterol. 2008, 42, 1117–1119. [Google Scholar] [CrossRef] [PubMed]
- Andreasen, A.S.; Larsen, N.; Pedersen-Skovsgaard, T.; Berg, R.M.; Moller, K.; Svendsen, K.D.; Jakobsen, M.; Pedersen, B.K. Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects. Br. J. Nutr. 2010, 104, 1831–1838. [Google Scholar] [CrossRef] [PubMed]
- Mahboobi, S.; Iraj, B.; Maghsoudi, Z.; Feizi, A.; Ghiasvand, R.; Askari, G.; Maayeshi, N. The effects of probiotic supplementation on markers of blood lipids, and blood pressure in patients with prediabetes: A randomized clinical trial. Int. J. Prev. Med. 2014, 5, 1239–1246. [Google Scholar] [PubMed]
- Lewis, S.J.; Burmeister, S. A double-blind placebo-controlled study of the effects of Lactobacillus acidophilus on plasma lipids. Eur. J. Clin. Nutr. 2005, 59, 776–780. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Zhang, H.; Chen, X.; Chen, Y.; MenghebiligeBao, Q. Selection of potential probiotic lactobacilli for cholesterol-lowering properties and their effect on cholesterol metabolism in rats fed a high-lipid diet. J. Dairy Sci. 2012, 95, 1645–1654. [Google Scholar] [CrossRef] [PubMed]
- An, H.M.; Park, S.Y.; Lee, D.K.; Kim, J.R.; Cha, M.K.; Lee, S.W.; Lim, H.T.; Kim, K.J.; Ha, N.J. Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats. Lipids Health Dis. 2011, 10, 116. [Google Scholar] [CrossRef] [PubMed]
- Gauffin Cano, P.; Santacruz, A.; Moya, A.; Sanz, Y. Bacteroides uniformis CECT 7771 ameliorates metabolic and immunological dysfunction in mice with high-fat-diet induced obesity. PLoS ONE 2012, 7, e41079. [Google Scholar] [CrossRef] [PubMed]
- Loguercio, C.; Federico, A.; Tuccillo, C.; Terracciano, F.; D’Auria, M.V.; De Simone, C.; Del Vecchio Blanco, C. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J. Clin. Gastroenterol. 2005, 39, 540–543. [Google Scholar] [PubMed]
- Al-Muzafar, H.M.; Amin, K.A. Probiotic mixture improves fatty liver disease by virtue of its action on lipid profiles, leptin, and inflammatory biomarkers. BMC Complement. Altern. Med. 2017, 17, 43. [Google Scholar] [CrossRef] [PubMed]
- Famouri, F.; Shariat, Z.; Hashemipour, M.; Keikha, M.; Kelishadi, R. Effects of Probiotics on Nonalcoholic Fatty Liver Disease in Obese Children and Adolescents. J. Pediatr. Gastroenterol. Nutr. 2017, 64, 413–417. [Google Scholar] [CrossRef] [PubMed]
- Wong, V.W.; Won, G.L.; Chim, A.M.; Chu, W.C.; Yeung, D.K.; Li, K.C.; Chan, H.L. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann. Hepatol. 2013, 12, 256–262. [Google Scholar] [PubMed]
- Nabavi, S.; Rafraf, M.; Somi, M.H.; Homayouni-Rad, A.; Asghari-Jafarabadi, M. Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease. J. Dairy Sci. 2014, 97, 7386–7393. [Google Scholar] [CrossRef] [PubMed]
- Ejtahed, H.S.; Mohtadi-Nia, J.; Homayouni-Rad, A.; Niafar, M.; Asghari-Jafarabadi, M.; Mofid, V.; Akbarian-Moghari, A. Effect of probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes mellitus. J. Dairy Sci. 2011, 94, 3288–3294. [Google Scholar] [CrossRef] [PubMed]
- Gibson, G.R.; Roberfroid, M.B. Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics. J. Nutr. 1995, 125, 1401–1412. [Google Scholar] [PubMed]
- Roberfroid, M. Prebiotics: The concept revisited. J. Nutr. 2007, 137, 830S–837S. [Google Scholar] [PubMed]
- Roberfroid, M.B. Inulin-type fructans: Functional food ingredients. J. Nutr. 2007, 137, 2493S–2502S. [Google Scholar] [PubMed]
- Parnell, J.A.; Raman, M.; Rioux, K.P.; Reimer, R.A. 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, 701–711. [Google Scholar] [CrossRef] [PubMed]
- Daubioul, C.A.; Horsmans, Y.; Lambert, P.; Danse, E.; Delzenne, N.M. Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: Results of a pilot study. Eur. J. Clin. Nutr. 2005, 59, 723–726. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Possemiers, S.; Van de Wiele, T.; Guiot, Y.; Everard, A.; Rottier, O.; Geurts, L.; Naslain, D.; Neyrinck, A.; Lambert, D.M.; et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009, 58, 1091–1103. [Google Scholar] [CrossRef] [PubMed]
- 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, e0175406. [Google Scholar] [CrossRef] [PubMed]
- Pachikian, B.D.; Essaghir, A.; Demoulin, J.B.; Catry, E.; Neyrinck, A.M.; Dewulf, E.M.; Sohet, F.M.; Portois, L.; Clerbaux, L.A.; Carpentier, Y.A.; et al. Prebiotic approach alleviates hepatic steatosis: Implication of fatty acid oxidative and cholesterol synthesis pathways. Mol. Nutr. Food Res. 2013, 57, 347–359. [Google Scholar] [CrossRef] [PubMed]
- Lau, E.; Carvalho, D.; Freitas, P. Gut Microbiota: Association with NAFLD and Metabolic Disturbances. Biomed. Res. Int. 2015, 2015, 979515. [Google Scholar] [CrossRef] [PubMed]
- Salminen, S.; Salminen, E. Lactulose, lactic acid bacteria, intestinal microecology and mucosal protection. Scand. J. Gastroenterol. Suppl. 1997, 222, 45–48. [Google Scholar] [CrossRef] [PubMed]
- Fan, J.G.; Xu, Z.J.; Wang, G.L. Effect of lactulose on establishment of a rat non-alcoholic steatohepatitis model. World J. Gastroenterol. 2005, 11, 5053–5056. [Google Scholar] [CrossRef] [PubMed]
- Neyrinck, A.M.; Possemiers, S.; Verstraete, W.; De Backer, F.; Cani, P.D.; Delzenne, N.M. 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, 51–59. [Google Scholar] [CrossRef] [PubMed]
- Singh, D.P.; Khare, P.; Zhu, J.; Kondepudi, K.K.; Singh, J.; Baboota, R.K.; Boparai, R.K.; Khardori, R.; Chopra, K.; Bishnoi, M. A novel cobiotic-based preventive approach against high-fat diet-induced adiposity, nonalcoholic fatty liver and gut derangement in mice. Int. J. Obes. (Lond.) 2016, 40, 487–496. [Google Scholar] [CrossRef] [PubMed]
- Micka, A.; Siepelmeyer, A.; Holz, A.; Theis, S.; Schon, C. Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: A randomized, double-blind, placebo-controlled trial. Int. J. Food Sci. Nutr. 2017, 68, 82–89. [Google Scholar] [CrossRef] [PubMed]
- Poesen, R.; Evenepoel, P.; de Loor, H.; Delcour, J.A.; Courtin, C.M.; 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, e0153893. [Google Scholar] [CrossRef] [PubMed]
- Lambert, J.E.; Parnell, J.A.; Eksteen, B.; Raman, M.; Bomhof, M.R.; Rioux, K.P.; Madsen, K.L.; Reimer, R.A. Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: A randomized controlled trial protocol. BMC Gastroenterol. 2015, 15, 169. [Google Scholar] [CrossRef] [PubMed]
- Mitchell, C.M.; Davy, B.M.; Halliday, T.M.; Hulver, M.W.; Neilson, A.P.; Ponder, M.A.; Davy, K.P. The effect of prebiotic supplementation with inulin on cardiometabolic health: Rationale, design, and methods of a controlled feeding efficacy trial in adults at risk of type 2 diabetes. Contemp. Clin. Trials 2015, 45, 328–337. [Google Scholar] [CrossRef] [PubMed]
- Savaiano, D.A.; Ritter, A.J.; Klaenhammer, T.R.; James, G.M.; Longcore, A.T.; Chandler, J.R.; Walker, W.A.; Foyt, H.L. Improving lactose digestion and symptoms of lactose intolerance with a novel galacto-oligosaccharide (RP-G28): A randomized, double-blind clinical trial. Nutr. J. 2013, 12, 160. [Google Scholar] [CrossRef] [PubMed]
- Holscher, H.D.; Faust, K.L.; Czerkies, L.A.; Litov, R.; Ziegler, E.E.; Lessin, H.; Hatch, T.; Sun, S.; Tappenden, K.A. Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. JPEN J. Parenter. Enteral Nutr. 2012, 36, 95S–105S. [Google Scholar] [CrossRef] [PubMed]
- Dewulf, E.M.; Cani, P.D.; Claus, S.P.; Fuentes, S.; Puylaert, P.G.; Neyrinck, A.M.; Bindels, L.B.; de Vos, W.M.; Gibson, G.R.; Thissen, J.P.; et al. Insight into the prebiotic concept: Lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut 2013, 62, 1112–1121. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Delzenne, N.M. The gut microbiome as therapeutic target. Pharmacol. Ther. 2011, 130, 202–212. [Google Scholar] [CrossRef] [PubMed]
- de Vrese, M.; Schrezenmeir, J. Probiotics, prebiotics, and synbiotics. Adv. Biochem. Eng. Biotechnol. 2008, 111, 1–66. [Google Scholar] [CrossRef] [PubMed]
- Pandey, K.R.; Naik, S.R.; Vakil, B.V. Probiotics, prebiotics and synbiotics- a review. J. Food Sci. Technol. 2015, 52, 7577–7587. [Google Scholar] [CrossRef] [PubMed]
- 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. Effects of a Lactobacillus paracasei B21060 based synbiotic on steatosis, insulin signaling and toll-like receptor expression in rats fed a high-fat diet. J. Nutr. Biochem. 2014, 25, 81–90. [Google Scholar] [CrossRef] [PubMed]
- Kassaian, N.; Aminorroaya, A.; Feizi, A.; Jafari, P.; Amini, M. The effects of probiotic and synbiotic supplementation on metabolic syndrome indices in adults at risk of type 2 diabetes: Study protocol for a randomized controlled trial. Trials 2017, 18, 148. [Google Scholar] [CrossRef] [PubMed]
- Saez-Lara, M.J.; Robles-Sanchez, C.; Ruiz-Ojeda, F.J.; 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, 928. [Google Scholar] [CrossRef] [PubMed]
- Furrie, E.; Macfarlane, S.; Kennedy, A.; Cummings, J.H.; Walsh, S.V.; O’Neil, D.A.; Macfarlane, G.T. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: A randomised controlled pilot trial. Gut 2005, 54, 242–249. [Google Scholar] [CrossRef] [PubMed]
- Eslamparast, T.; Poustchi, H.; Zamani, F.; Sharafkhah, M.; Malekzadeh, R.; Hekmatdoost, A. Synbiotic supplementation in nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled pilot study. Am. J. Clin. Nutr. 2014, 99, 535–542. [Google Scholar] [CrossRef] [PubMed]
- Malaguarnera, M.; Vacante, M.; Antic, T.; Giordano, M.; Chisari, G.; Acquaviva, R.; Mastrojeni, S.; Malaguarnera, G.; Mistretta, A.; Li Volti, G.; et al. Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig. Dis. Sci. 2012, 57, 545–553. [Google Scholar] [CrossRef] [PubMed]
- 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, 662–668. [Google Scholar] [CrossRef] [PubMed]
- Asgharian, A.; Askari, G.; Esmailzade, A.; Feizi, A.; Mohammadi, V. The Effect of Symbiotic Supplementation on Liver Enzymes, C-reactive Protein and Ultrasound Findings in Patients with Non-alcoholic Fatty Liver Disease: A Clinical Trial. Int. J. Prev. Med. 2016, 7, 59. [Google Scholar] [CrossRef] [PubMed]
- Goffredo, M.; Mass, K.; Parks, E.J.; Wagner, D.A.; McClure, E.A.; Graf, J.; Savoye, M.; Pierpont, B.; Cline, G.; Santoro, N. Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth. J. Clin. Endocrinol. Metab. 2016, 101, 4367–4376. [Google Scholar] [CrossRef] [PubMed]
- Zhou, J.; Gao, S.; Chen, J.; Zhao, R.; Yang, X. Maternal sodium butyrate supplement elevates the lipolysis in adipose tissue and leads to lipid accumulation in offspring liver of weaning-age rats. Lipids Health Dis. 2016, 15, 119. [Google Scholar] [CrossRef] [PubMed]
- Zhou, D.; Pan, Q.; Xin, F.Z.; Zhang, R.N.; He, C.X.; Chen, G.Y.; Liu, C.; Chen, Y.W.; Fan, J.G. Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier. World J. Gastroenterol. 2017, 23, 60–75. [Google Scholar] [CrossRef] [PubMed]
- Jernberg, C.; Lofmark, S.; Edlund, C.; Jansson, J.K. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007, 1, 56–66. [Google Scholar] [CrossRef] [PubMed]
- Wu, W.-C. Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats. World J. Gastroenterol. 2008, 14, 313. [Google Scholar] [CrossRef] [PubMed]
- Gangarapu, V.; Ince, A.T.; Baysal, B.; Kayar, Y.; Kilic, U.; Gok, O.; Uysal, O.; Senturk, H. Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease. Eur. J. Gastroenterol. Hepatol. 2015, 27, 840–845. [Google Scholar] [CrossRef] [PubMed]
- Singh, R.; Sripada, L. Side effects of antibiotics during bacterial infection: Mitochondria, the main target in host cell. Mitochondrion 2014, 16, 50–54. [Google Scholar] [CrossRef] [PubMed]
- Zhong, L.J.; Xie, Z.S.; Yang, H.; Li, P.; Xu, X.J. Moutan Cortex and Paeoniae Radix Rubra reverse high-fat-diet-induced metabolic disorder and restore gut microbiota homeostasis. Chin. J. Nat. Med. 2017, 15, 210–219. [Google Scholar] [CrossRef]
- Xu, J.; Chen, H.B.; Li, S.L. Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota. Med. Res. Rev. 2017, 37, 1140–1185. [Google Scholar] [CrossRef] [PubMed]
- 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, 931–937. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Zhao, Y.; Zhang, M.; Pang, X.; Xu, J.; Kang, C.; Li, M.; Zhang, C.; Zhang, Z.; Zhang, Y.; et al. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS ONE 2012, 7, e42529. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; He, J.Z.; Zhou, X.D.; Xu, X. Berberine regulates type 2 diabetes mellitus related with insulin resistance. Zhongguo Zhong Yao Za Zhi 2017, 42, 2254–2260. [Google Scholar] [CrossRef] [PubMed]
- Xu, J.H.; Liu, X.Z.; Pan, W.; Zou, D.J. Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels. Mol. Med. Rep. 2017, 15, 2765–2787. [Google Scholar] [CrossRef] [PubMed]
- Cao, Y.; Pan, Q.; Cai, W.; Shen, F.; Chen, G.Y.; Xu, L.M.; Fan, J.G. Modulation of Gut Microbiota by Berberine Improves Steatohepatitis in High-Fat Diet-Fed BALB/C Mice. Arch. Iran. Med. 2016, 19, 197–203. [Google Scholar]
- Xie, W.; Gu, D.; Li, J.; Cui, K.; Zhang, Y. Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice. PLoS ONE 2011, 6, e24520. [Google Scholar] [CrossRef] [PubMed]
- Lin, P.; Lu, J.; Wang, Y.; Gu, W.; Yu, J.; Zhao, R. Naturally Occurring Stilbenoid TSG Reverses Non-Alcoholic Fatty Liver Diseases via Gut-Liver Axis. PLoS ONE 2015, 10, e0140346. [Google Scholar] [CrossRef] [PubMed]
- Varshney, P.; Dey, C.S. Resveratrol regulates neuronal glucose uptake and insulin sensitivity via P21-activated kinase 2 (PAK2). Biochem. Biophys. Res. Commun. 2017, 485, 372–378. [Google Scholar] [CrossRef] [PubMed]
- Qiao, Y.; Sun, J.; Xia, S.; Tang, X.; Shi, Y.; Le, G. Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity. Food Funct. 2014, 5, 1241–1249. [Google Scholar] [CrossRef] [PubMed]
- 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, 188–196. [Google Scholar] [CrossRef] [PubMed]
- Feng, Q.; Liu, W.; Baker, S.S.; Li, H.; Chen, C.; Liu, Q.; Tang, S.; Guan, L.; Tsompana, M.; Kozielski, R.; et al. Multi-targeting therapeutic mechanisms of the Chinese herbal medicine QHD in the treatment of non-alcoholic fatty liver disease. Oncotarget 2017, 8, 27820–27838. [Google Scholar] [CrossRef] [PubMed]
- Hussain, A.; Yadav, M.K.; Bose, S.; Wang, J.H.; Lim, D.; Song, Y.K.; Ko, S.G.; 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, e0165483. [Google Scholar] [CrossRef] [PubMed]
- Yuan, Y.; Sun, Z.M.; Zhang, Y.; Liang, F.F.; He, X.X. Influence of gut microecology on the pathogenesis and treatment of nonalcoholic fatty liver disease. Zhonghua Gan Zang Bing Za Zhi 2016, 24, 375–379. [Google Scholar] [CrossRef] [PubMed]
- Xu, J.; Lian, F.; Zhao, L.; Zhao, Y.; Chen, X.; Zhang, X.; Guo, Y.; Zhang, C.; Zhou, Q.; Xue, Z.; et al. Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula. ISME J. 2015, 9, 552–562. [Google Scholar] [CrossRef] [PubMed]
Interventions | Main Effects | Experimental Models | Ref. | |
---|---|---|---|---|
Probiotic | Lactobacillus (LcS) | Suppressing NASH development | MCD diet-induced NASH in mice | [64] |
Improving insulin resistance and glucose intolerance | Diet-induced obesity (DIO) mice. | [65] | ||
Protecting against the onset of fructose-induced NAFLD | Fructose-induced NAFLD in mice | [66] | ||
L. paracasei | Attenuating hepatic steatosis | (High fat +10% fructose diet)-induced NASH in mice | [70] | |
L. plantarum A7 | Lowering serum lipids, TC, and TG levels | High-cholesterol diet-fed rats | [73] | |
L. plantarum MA2 | Lowering serum TC, TG and low-density lipoprotein cholesterol | Cholesterol-enriched diet-fed rats | [74] | |
L. plantarum NCU116 | Improving liver function, oxidative stress and lipid metabolism | HFD-induced NAFLD in rats | [75] | |
Lactobacillus rhamnosus GG (LGG) | Protecting mice from NAFLD attenuated liver inflammation and steatosis | High-fructose diet induced NAFLD in mice | [76] | |
Improving NAFLD | HFD-induced NAFLD in rats | [82] | ||
Improving in alanine aminotransferase levels | 20 obesity-related liver abnormalities in children | [105] | ||
L. johnsonii BS15 | Effective in preventing NAFLD | HFD-induced NAFLD in mice | [78] | |
L. reuteri GMNL-263 | Ameliorating hepatic steatosis | High-fructose diet-fed rats | [79] | |
L. gasseri BNR17 | Inhibiting increases in body and adipocyte tissue weight | High-sucrose diet-induced obese mice. | [80] | |
3 Lactobacillus strains | Reducing serum TC, TG, and low-density lipoprotein cholesterol | HFD-fed rats | [114] | |
L. acidophilus NCFM | Inflammatory markers and the systemic inflammatory response were unaffected | 45 males with T2D | [111] | |
L. acidophilus | No changes in serum lipids | 80 patients with elevated cholesterols | [113] | |
Bifidobacterium (Bif) | Ameliorating visceral fat accumulation and insulin sensitivity | HFD-fed rats | [84] | |
Attenuating hepatic fat accumulation | HFD-induced NAFLD in rats | [86] | ||
Reducing body and fat weights, blood serum levels (TC, HDL-C, LDL-C, TG, AST, ALT, and lipase levels) | HFD-induced obesity in rats | [115] | ||
B. pseudocatenulatum CECT 7765 | Reducing serum cholesterol, TG, and insulin resistance | HFD-fed mice | [85] | |
Bacteroides uniformis CECT 7771 | Reducing body weight gain, liver steatosis and cholesterol and TG concentrations | HFD-induced obesity mice | [116] | |
Probiotic | VSL#3 | Limiting oxidative and inflammatory liver damage | HFD-fed young rats | [92] |
Reducing hepatic total fatty acid content and ALT levels. | HFD-induced NAFLD in mice | [93] | ||
Improvements in steatosis and insulin resistance | HFD-fed mice | [94] | ||
Modulating liver fibrosis, without protecting from inflammation and steatosis in NASH. | MCD diet-induced NASH in mice. | [95] | ||
Improving the degree of liver disease in children | 44 Obese children with NAFLD | [104] | ||
Improving plasma levels of lipid peroxidation markers: MDA(malondialdehyde), 4-HNE( 4-hydroxynonenal). | 22 patients with NAFLD + 20 patients with AC (alcoholic liver cirrhosis ) | [117] | ||
Experiencing a significant increase in liver fat; no significant differences in any of the blood assays or clinical parameters | 4 patients with NAFLD | [110] | ||
Probiotic mixtures | Improving NAFLD | HFD-induced NAFLD in rats | [96] | |
Delaying the progression of NAFLD via LPS/TLR4 signaling | HSHF diet-induced NAFLD in rats | [97] | ||
Improving NAFLD pathogenesis and steatosis | High fat and sucrose diet (HFSD)-induced NAFLD in rats | [118] | ||
Influencing protein expression and decreasing steatohepatitis | MCD diet-induced NASH in rats | [99] | ||
Reducing obesity-related biomarkers and modulating the microbial community | Obese mice | [100] | ||
Modulating gut microbiota and up-regulated genes related to fatty acid oxidation in both the liver and adipose tissue | HFD-induced obese mice | [98] | ||
Improving liver aminotransferases levels | 30 patients with NAFLD | [106] | ||
Decreasing levels of ALT and AST and improving pediatric NAFLD | 64 obese children with NAFLD | [119] | ||
Reducing insulin, insulin resistance, TNF-a, and IL-6 | 42 patients with NAFLD | [107] | ||
No significant changes in (LDL)-cholesterol, (HDL)-cholesterol, TG, TC TG/LDL and LDL/HDL ratios | 60 patients with T2DM | [112] | ||
Great reductions in serum AST level and liver fat | 20 patients with NASH | [120] | ||
MIYAIRI 588 | Improving NAFLD and decreasing accumulation of lipid droplets | HFD-induced NAFLD in rats | [102] | |
Improving hepatic lipid deposition and decreasing the triglyceride content, insulin resistance, serum endotoxin levels, and hepatic inflammatory indexes. | Choline-deficient/ l-amino acid-defined (CDAA)-diet-induced NAFLD in rats | [103] | ||
Probiotics and metformin | Improvements in liver aminotransferases, cholesterol, and TG | 64 patients with NASH | [108] | |
Probiotics and statins | Lowering cholesterol and products of metabolism of intestinal microflora | Patients with NAFLD | [109] | |
Probiotic | Probiotic yogurt | Improving hepatic enzymes, serum TC, and low-density lipoprotein cholesterol levels | 72 patients with NAFLD | [121] |
Improvements in total cholesterol and LDL-C concentrations | 60 people with type 2 diabetes and low-density lipoprotein cholesterol | [122] |
Interventions | Main Effects | Experimental Models | Ref. | |
---|---|---|---|---|
Prebiotic | Oligofructose (OFS) | Lowering LPS and cytokine levels, and decreasing the hepatic expression of inflammatory and oxidative stress markers | Obese and diabetic mice | [128] |
Decreasing serum ALT, AST and insulin level | Patients with NASH | [127] | ||
Fructooligosaccharides (FOS) | Restoring normal gastrointestinal microflora and intestinal epithelial barrier function, and decreasing steatohepatitis | MCD diet-induced NASH in mice. | [129] | |
Reducing hepatic TG and TC level, modulating hepatic steatosis | N-3PUFA (polyunsaturated fatty acid)-depleted diet-fed mice | [130] | ||
Lactulose | Ameliorating the hepatic inflammation and decreasing serum levels of ALT and AST | HFD-induced NASH in rats | [133] | |
Chitin–glucan (CG) | Decreasing weight gain, fat mass development, glucose intolerance, and hepatic TG accumulation | HFD-induced obese mice | [134] | |
Isomalto-oligosaccharides (IMOs) | Preventing weight gain, adiposity, and improving insulin resistance. | HFD-induced NAFLD in mice | [135] | |
Galacto-oligosaccharides and fructo-oligosaccharides (9:1) | Increasing abundance and proportion of bifidobacteria | Formula-fed infants (FF) | [141] | |
Inulin-type fructans( ITF) prebiotics (inulin + oligofructose) | Changing the gut microbiota composition and host metabolism | 30 obese women | [142] |
Interventions | Main Effects | Experimental Models | Ref. | |
---|---|---|---|---|
Synbiotic | L. paracasei B21060 + arabinogalactan + FOS | Lessening NAFLD progression, preserving gut barrier integrity and reducing the severity of liver injury and IR | HFD-induced NAFLD in rats | [146] |
Seven probiotics + OFS | Improving NAFLD and decreasing levels of ALT and AST | 52 patients with NAFLD | [150] | |
B. longum + FOS | Reductions in TNF-a, serum AST levels, serum endotoxins, steatosis, and the NASH activity index | 66 patients with NASH | [151] | |
Dietary fiber + L. reuteri | Improving NAFLD and reducing serum levels of most of the inflammatory mediators | 50 lean patients with NAFLD | [152] | |
Seven probiotics + FOS | Protecting against NAFLD progression and improving steatosis | 80 NAFLD patients | [153] |
Interventions | Main Effects | Experimental Models | Ref. | |
---|---|---|---|---|
Antibiotic | Cidomycin | Lowering serum levels of ALT, AST and TNF-α and alleviating the severity of NASH | Rats with NASH | [158] |
Vancomycin + Neomycin + Metronidazole + Ampicillin | Adjusting gut microecology and alleviating the lesions of NAFLD | HFD-induced NAFLD in rats | [175] | |
Rifaximin | Improving NAFLD and reducing endotoxin and IL-10 levels | 42 patients with NAFLD | [159] | |
Herbal medicine or natural active ingredient | 2,3,5,4′-tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG) | Reversing NAFLD and reducing FFA accumulation, and increasing the protein expression of ZO-1 and occludin | HFD-induced NAFLD in rats | [169] |
Resveratrol | Reducing blood glucose and lipid levels, and lowering both body and visceral adipose weights | HFD-fed mice | [171] | |
Qushi Huayu Fang | Reducing body weight, TG and free fatty acids, alleviating hepatic steatosis | HFD-induced NAFLD in rats | [172] | |
Enhancing the hepatic anti-oxidative mechanism, decreasing hepatic lipid synthesis, and promoting the regulatory T cell inducing microbiota in the gut | HFD-induced NAFLD in rats | [173] | ||
Daesiho-tang (DSHT) | Ameliorating body weight gain, body fat, decreasing TC and TG | HFD-fed obese mice | [174] | |
Gegen Qinlian Decoction (GQD) | Alleviating T2D, increasing the amounts of beneficial bacteria | 187 patients with type 2 diabetes (T2D) | [176] |
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Ma, J.; Zhou, Q.; Li, H. Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanisms and Therapy. Nutrients 2017, 9, 1124. https://doi.org/10.3390/nu9101124
Ma J, Zhou Q, Li H. Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanisms and Therapy. Nutrients. 2017; 9(10):1124. https://doi.org/10.3390/nu9101124
Chicago/Turabian StyleMa, Junli, Qihang Zhou, and Houkai Li. 2017. "Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanisms and Therapy" Nutrients 9, no. 10: 1124. https://doi.org/10.3390/nu9101124
APA StyleMa, J., Zhou, Q., & Li, H. (2017). Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanisms and Therapy. Nutrients, 9(10), 1124. https://doi.org/10.3390/nu9101124