{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:28:33Z","timestamp":1789122513515,"version":"build-2803163510"},"reference-count":98,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria play a crucial role in the pathogenesis and progression of liver damage in patients with NAFLD, it has been suggested that manipulating the microbiome may represent a therapeutical option. In this review, we summarise the latest evidence supporting the manipulation of the intestinal microbiome as a potential therapy for treating liver disease in patients with NAFLD.<\/jats:p>","DOI":"10.3390\/ijms23158307","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T21:11:05Z","timestamp":1658956265000},"page":"8307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Gut Microbiota\u2014A Future Therapeutic Target for People with Non-Alcoholic Fatty Liver Disease: A Systematic Review"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-7065","authenticated-orcid":false,"given":"Roberta","family":"Forlano","sequence":"first","affiliation":[{"name":"Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6847-7599","authenticated-orcid":false,"given":"Mathuri","family":"Sivakumar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-3100","authenticated-orcid":false,"given":"Benjamin H.","family":"Mullish","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinelopi","family":"Manousou","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis","volume":"69","author":"Younossi","year":"2019","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s43440-019-00020-1","article-title":"New therapeutic strategies in nonalcoholic fatty liver disease: A focus on promising drugs for nonalcoholic steatohepatitis","volume":"72","author":"Pydyn","year":"2020","journal-title":"Pharm. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrgastro.2013.34","article-title":"NAFLD in Asia\u2014As common and important as in the West","volume":"10","author":"Farrell","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4254\/wjh.v9.i16.715","article-title":"Non-alcoholic fatty liver disease: An expanded review","volume":"9","author":"Benedict","year":"2017","journal-title":"World J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/j.1467-789X.2009.00657.x","article-title":"Non-alcoholic fatty liver disease from pathogenesis to management: An update","volume":"11","author":"Musso","year":"2010","journal-title":"Obes. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.21037\/tgh.2019.09.08","article-title":"Epidemiology of non-alcoholic and alcoholic fatty liver diseases","volume":"5","author":"Mitra","year":"2020","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100234","DOI":"10.1016\/j.jhepr.2021.100234","article-title":"European \u2018NAFLD Preparedness Index\u2019\u2014Is Europe ready to meet the challenge of fatty liver disease?","volume":"3","author":"Lazarus","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/hep.27368","article-title":"Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up","volume":"61","author":"Ekstedt","year":"2015","journal-title":"Hepatology"},{"key":"ref_9","unstructured":"Le, M.H., Yeo, Y.H., Li, X., Li, J., Zou, B., Wu, Y., Ye, Q., Huang, D.Q., Zhao, C., and Zhang, J. (2021). 2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis. Clin. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1053\/jhep.2003.50161","article-title":"Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome","volume":"37","author":"Marchesini","year":"2003","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) (2016). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia, 59, 1121\u20131140.","DOI":"10.1007\/s00125-016-3902-y"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.cgh.2009.05.033","article-title":"Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease","volume":"7","author":"Shah","year":"2009","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/s41598-018-19753-9","article-title":"Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance","volume":"8","author":"Teterina","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.cmet.2020.06.005","article-title":"A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis","volume":"32","author":"Oh","year":"2020","journal-title":"Cell Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrgastro.2016.85","article-title":"The role of the gut microbiota in NAFLD","volume":"13","author":"Leung","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_16","unstructured":"Beyaz Coskun, A., and Sagdicoglu Celep, A.G. (2021). Therapeutic modulation methods of gut microbiota and gut-liver axis. Crit. Rev. Food Sci. Nutr., 1\u201311."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1136\/flgastro-2019-101376","article-title":"The gut microbiome: What every gastroenterologist needs to know","volume":"12","author":"Mullish","year":"2021","journal-title":"Frontline Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sender, R., Fuchs, S., and Milo, R. (2016). Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol., 14.","DOI":"10.1101\/036103"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.cell.2006.02.017","article-title":"Ecological and evolutionary forces shaping microbial diversity in the human intestine","volume":"124","author":"Ley","year":"2006","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G.A.D., Gasbarrini, A., and Mele, M.C. (2019). What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms, 7.","DOI":"10.3390\/microorganisms7010014"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s10620-020-06112-w","article-title":"Diet and the Human Gut Microbiome: An International Review","volume":"65","author":"Wilson","year":"2020","journal-title":"Dig. Dis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1136\/gut.48.2.206","article-title":"The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis","volume":"48","author":"Wigg","year":"2001","journal-title":"Gut"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/nature05414","article-title":"An obesity-associated gut microbiome with increased capacity for energy harvest","volume":"444","author":"Turnbaugh","year":"2006","journal-title":"Nature"},{"key":"ref_24","first-page":"2416","article-title":"Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice","volume":"22","author":"Membrez","year":"2008","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1053\/j.gastro.2012.06.031","article-title":"Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome","volume":"143","author":"Vrieze","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/s41591-018-0061-3","article-title":"Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women","volume":"24","author":"Hoyles","year":"2018","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41575-020-0269-9","article-title":"Gut microbiota and human NAFLD: Disentangling microbial signatures from metabolic disorders","volume":"17","author":"Vigliotti","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/s41598-020-79718-9","article-title":"Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients","volume":"11","author":"Lanthier","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1080\/19490976.2019.1681861","article-title":"Lower gut microbiome diversity and higher abundance of proinflammatory genus Collinsella are associated with biopsy-proven nonalcoholic steatohepatitis","volume":"11","author":"Astbury","year":"2020","journal-title":"Gut MicrObes"},{"key":"ref_30","first-page":"381","article-title":"Update on the Role of the Gut Microbiota on Alcohol-Associated Liver Disease","volume":"17","author":"Schnabl","year":"2021","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1111\/j.1462-2920.2009.01931.x","article-title":"The role of pH in determining the species composition of the human colonic microbiota","volume":"11","author":"Duncan","year":"2009","journal-title":"Environ. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16452","DOI":"10.3748\/wjg.v20.i44.16452","article-title":"Obesity, fatty liver disease and intestinal microbiota","volume":"20","author":"Arslan","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.2337\/dc10-0556","article-title":"Obesity, diabetes, and gut microbiota: The hygiene hypothesis expanded?","volume":"33","author":"Musso","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1126\/science.1242674","article-title":"Immunology. Feed your Tregs more fiber","volume":"341","author":"Bollrath","year":"2013","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature12721","article-title":"Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells","volume":"504","author":"Furusawa","year":"2013","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.2337\/db14-1213","article-title":"Short-Chain Fatty Acids Protect Against High-Fat Diet-Induced Obesity via a PPARgamma-Dependent Switch From Lipogenesis to Fat Oxidation","volume":"64","author":"Bleeker","year":"2015","journal-title":"Diabetes"},{"key":"ref_37","first-page":"46","article-title":"Dietary intake, energy metabolism, and excretory losses of adult male germfree Wistar rats","volume":"33","author":"Wostmann","year":"1983","journal-title":"Lab. Anim. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3945\/ajcn.110.010132","article-title":"Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans","volume":"94","author":"Jumpertz","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/hep.26319","article-title":"Intestinal microbiota in patients with nonalcoholic fatty liver disease","volume":"58","author":"Mouzaki","year":"2013","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"G589","DOI":"10.1152\/ajpgi.00488.2011","article-title":"Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine","volume":"303","author":"Derrien","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1042\/bj2990725","article-title":"Effect of cyclodextrins and undigested starch on the loss of chenodeoxycholate in the faeces","volume":"299","author":"Abadie","year":"1994","journal-title":"Biochem. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s11745-009-3300-z","article-title":"Common variants of ABCB4 and ABCB11 and plasma lipid levels: A study in sib pairs with gallstones, and controls","volume":"44","author":"Acalovschi","year":"2009","journal-title":"Lipids"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1007\/s00232-014-9715-3","article-title":"The mechanism of enterohepatic circulation in the formation of gallstone disease","volume":"247","author":"Cai","year":"2014","journal-title":"J. Membr. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s41575-021-00502-9","article-title":"Metabolomics and lipidomics in NAFLD: Biomarkers and non-invasive diagnostic tests","volume":"18","author":"Masoodi","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.12688\/f1000research.12449.1","article-title":"Recent advances in understanding bile acid homeostasis","volume":"6","author":"Chiang","year":"2017","journal-title":"F1000Research"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.17140\/LROJ-1-106","article-title":"Non-Alcoholic Fatty Liver Disease: The Effect of Bile Acids and Farnesoid X Receptor Agonists on Pathophysiology and Treatment","volume":"1","author":"Khalid","year":"2015","journal-title":"Liver Res. Open J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1097\/MEG.0b013e328345c8c7","article-title":"Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis","volume":"23","author":"Dasarathy","year":"2011","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/MEG.0b013e3282f4710a","article-title":"Bile acid levels are increased in the liver of patients with steatohepatitis","volume":"20","author":"Aranha","year":"2008","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1985.e4","DOI":"10.1053\/j.gastro.2020.07.050","article-title":"Screening for Nonalcoholic Fatty Liver Disease in Persons with Type 2 Diabetes in the United States Is Cost-effective: A Comprehensive Cost-Utility Analysis","volume":"159","author":"Noureddin","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.cmet.2009.02.002","article-title":"A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance","volume":"9","author":"Newgard","year":"2009","journal-title":"Cell Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/hep.29359","article-title":"The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids","volume":"67","author":"Puri","year":"2018","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1210\/jc.2017-01397","article-title":"Bile Acid Alterations Are Associated With Insulin Resistance, but Not With NASH, in Obese Subjects","volume":"102","author":"Legry","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.taap.2013.01.022","article-title":"Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease","volume":"268","author":"Lake","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15718","DOI":"10.1073\/pnas.0407076101","article-title":"The gut microbiota as an environmental factor that regulates fat storage","volume":"101","author":"Backhed","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"ref_56","first-page":"3648","article-title":"Intestinal mucosal barrier dysfunction participates in the progress of nonalcoholic fatty liver disease","volume":"8","author":"Mao","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0006-3002(56)90148-2","article-title":"The formation of ethanol in Escherichia coli","volume":"22","author":"Dawes","year":"1956","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/hep.26093","article-title":"Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH","volume":"57","author":"Zhu","year":"2013","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/S0168-8278(00)80242-1","article-title":"Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease","volume":"32","author":"Parlesak","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.celrep.2018.03.109","article-title":"Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages","volume":"23","author":"Krishnan","year":"2018","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1136\/gutjnl-2018-316307","article-title":"Small metabolites, possible big changes: A microbiota-centered view of non-alcoholic fatty liver disease","volume":"68","author":"Chu","year":"2019","journal-title":"Gut"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1093\/cid\/civ177","article-title":"New approaches for bacteriotherapy: Prebiotics, new-generation probiotics, and synbiotics","volume":"60","author":"Patel","year":"2015","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nature12480","article-title":"Dietary intervention impact on gut microbial gene richness","volume":"500","author":"Cotillard","year":"2013","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"608498","DOI":"10.3389\/fimmu.2021.608498","article-title":"Toll-like receptors recognize intestinal microbes in liver cirrhosis","volume":"12","author":"Fan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cell.2013.12.016","article-title":"Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits","volume":"156","author":"Goncalves","year":"2014","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.cell.2012.05.016","article-title":"Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human","volume":"150","author":"Wu","year":"2012","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/nm.3361","article-title":"Brown and beige fat: Development, function and therapeutic potential","volume":"19","author":"Harms","year":"2013","journal-title":"Nat. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.cmet.2017.08.019","article-title":"Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota","volume":"26","author":"Li","year":"2017","journal-title":"Cell Metab."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Corb Aron, R.A., Abid, A., Vesa, C.M., Nechifor, A.C., Behl, T., Ghitea, T.C., Munteanu, M.A., Fratila, O., Andronie-Cioara, F.L., and Toma, M.M. (2021). Recognizing the Benefits of Pre-\/Probiotics in Metabolic Syndrome and Type 2 Diabetes Mellitus Considering the Influence of Akkermansia muciniphila as a Key Gut Bacterium. Microorganisms, 9.","DOI":"10.3390\/microorganisms9030618"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1126\/science.1110591","article-title":"Diversity of the human intestinal microbial flora","volume":"308","author":"Eckburg","year":"2005","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7577","DOI":"10.1007\/s13197-015-1921-1","article-title":"Probiotics, prebiotics and synbiotics\u2014A review","volume":"52","author":"Pandey","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/4441022a","article-title":"Microbial ecology: Human gut micrObes. associated with obesity","volume":"444","author":"Ley","year":"2006","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S164","DOI":"10.1002\/jcph.1121","article-title":"Probiotics in Disease Prevention and Treatment","volume":"58","author":"Liu","year":"2018","journal-title":"J. Clin. Pharm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"905","DOI":"10.3945\/jn.108.101808","article-title":"Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats","volume":"139","author":"Esposito","year":"2009","journal-title":"J. Nutr."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Bhathena, J., Martoni, C., Kulamarva, A., Tomaro-Duchesneau, C., Malhotra, M., Paul, A., Urbanska, A.M., and Prakash, S. (2013). Oral probiotic microcapsule formulation ameliorates non-alcoholic fatty liver disease in Bio F1B Golden Syrian hamsters. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058394"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"45176","DOI":"10.1038\/srep45176","article-title":"Probiotics may delay the progression of nonalcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia","volume":"7","author":"Xue","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"16894","DOI":"10.1038\/s41598-020-73670-4","article-title":"Pathophysiology of high fat diet induced obesity: Impact of probiotic banana juice on obesity associated complications and hepatosteatosis","volume":"10","author":"Konda","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5688","DOI":"10.1038\/s41598-019-42059-3","article-title":"Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease","volume":"9","author":"Ahn","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s10620-011-1887-4","article-title":"Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis","volume":"57","author":"Malaguarnera","year":"2012","journal-title":"Dig. Dis. Sci."},{"key":"ref_80","first-page":"1090","article-title":"Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: A double blind randomized clinical trial","volume":"15","author":"Aller","year":"2011","journal-title":"Eur. Rev. Med. Pharm. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3945\/ajcn.113.068890","article-title":"Synbiotic supplementation in nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled pilot study","volume":"99","author":"Eslamparast","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1017\/S0007114517000204","article-title":"Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: A pilot, randomised, double-blind, placebo-controlled, clinical trial","volume":"117","author":"Mofidi","year":"2017","journal-title":"Br. J. Nutr."},{"key":"ref_83","first-page":"e000315","article-title":"High potency multistrain probiotic improves liver histology in non-alcoholic fatty liver disease (NAFLD): A randomised, double-blind, proof of concept study","volume":"6","author":"Duseja","year":"2019","journal-title":"BMJ OpenGastroenterol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1597.e1597","DOI":"10.1053\/j.gastro.2020.01.031","article-title":"Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease","volume":"158","author":"Scorletti","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1159\/000443361","article-title":"The Role of Antibiotics in Gut Microbiota Modulation: The Eubiotic Effects of Rifaximin","volume":"34","author":"Ponziani","year":"2016","journal-title":"Dig. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.jhep.2008.01.035","article-title":"Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: Role of endotoxin","volume":"48","author":"Bergheim","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"38161","DOI":"10.18632\/oncotarget.16975","article-title":"Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic fatty liver disease induced by high fat diet in mice","volume":"8","author":"Hu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/hepr.12904","article-title":"Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study","volume":"48","author":"Cobbold","year":"2018","journal-title":"Hepatol. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1097\/MEG.0000000000000348","article-title":"Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease","volume":"27","author":"Gangarapu","year":"2015","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.4254\/wjh.v13.i12.2104","article-title":"Liver function tests and metabolic-associated fatty liver disease: Changes in upper normal limits, does it really matter?","volume":"13","author":"Forlano","year":"2021","journal-title":"World J. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1128\/microbiolspec.BAD-0008-2017","article-title":"Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile","volume":"5","author":"Bakker","year":"2017","journal-title":"Microbiol. Spectr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1241214","DOI":"10.1126\/science.1241214","article-title":"Gut microbiota from twins discordant for obesity modulate metabolism in mice","volume":"341","author":"Ridaura","year":"2013","journal-title":"Science"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1126\/science.1243787","article-title":"Microbiology. Fighting obesity with bacteria","volume":"341","author":"Walker","year":"2013","journal-title":"Science"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1038\/s41598-017-01751-y","article-title":"Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota","volume":"7","author":"Zhou","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"611.e616","DOI":"10.1016\/j.cmet.2017.09.008","article-title":"Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition","volume":"26","author":"Kootte","year":"2017","journal-title":"Cell Metab."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/s41591-021-01399-2","article-title":"Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: A randomized double-blind, placebo-controlled phase 2 trial","volume":"27","author":"Mocanu","year":"2021","journal-title":"Nat. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.14309\/ajg.0000000000000661","article-title":"Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial","volume":"115","author":"Craven","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"490","DOI":"10.21037\/atm.2017.10.03","article-title":"Transfer of altered behaviour and irritable bowel syndrome with diarrhea (IBS-D) through fecal microbiota transplant in mouse model indicates need for stricter donor screening criteria","volume":"5","author":"Craven","year":"2017","journal-title":"Ann. Transl. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8307\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:57:38Z","timestamp":1760140658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,27]]},"references-count":98,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158307"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158307","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,27]]}}}