{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T02:27:43Z","timestamp":1793845663750,"version":"4.6.1"},"reference-count":93,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"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>Inflammatory bowel diseases (IBD), comprising Crohn\u2019s disease and ulcerative colitis, are systemic and multifaceted disorders which affect other organs in addition to the gastrointestinal tract in up to 50% of cases. Extraintestinal manifestations may present before or after IBD diagnosis and negatively impact the intestinal disease course and patients\u2019 quality of life, often requiring additional diagnostic evaluations or specific treatments. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Current evidence shows an increased prevalence of NAFLD (and its more advanced stages, such as liver fibrosis and steatohepatitis) in IBD patients compared to the general population. Many different IBD-specific etiopathogenetic mechanisms have been hypothesized, including chronic inflammation, malabsorption, previous surgical interventions, changes in fecal microbiota, and drugs. However, the pathophysiological link between these two diseases is still poorly understood. In this review, we aim to provide a comprehensive overview of the potential mechanisms which have been investigated so far and highlight open issues still to be addressed for future studies.<\/jats:p>","DOI":"10.3390\/ijms25063278","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T05:43:08Z","timestamp":1710394988000},"page":"3278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Inflammatory Bowel Diseases and Non-Alcoholic Fatty Liver Disease: Piecing a Complex Puzzle Together"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1472-0039","authenticated-orcid":false,"given":"Rossella","family":"Maresca","sequence":"first","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Catholic University of Rome, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8192-631X","authenticated-orcid":false,"given":"Irene","family":"Mignini","sequence":"additional","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Catholic University of Rome, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8467-9491","authenticated-orcid":false,"given":"Simone","family":"Varca","sequence":"additional","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Catholic University of Rome, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2528-8337","authenticated-orcid":false,"given":"Valentin","family":"Calvez","sequence":"additional","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Catholic University of Rome, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0406-2705","authenticated-orcid":false,"given":"Fabrizio","family":"Termite","sequence":"additional","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Catholic University of Rome, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8296-168X","authenticated-orcid":false,"given":"Giorgio","family":"Esposto","sequence":"additional","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Catholic University of Rome, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5515-1197","authenticated-orcid":false,"given":"Lucrezia","family":"Laterza","sequence":"additional","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. 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Gemelli\u201d IRCCS, Catholic University of Rome, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6230-1779","authenticated-orcid":false,"given":"Antonio","family":"Gasbarrini","sequence":"additional","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Catholic University of Rome, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-9542","authenticated-orcid":false,"given":"Maria Assunta","family":"Zocco","sequence":"additional","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. 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Crohns Colitis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1097\/MIB.0000000000000429","article-title":"Chronological Order of Appearance of Extraintestinal Manifestations Relative to the Time of IBD Diagnosis in the Swiss Inflammatory Bowel Disease Cohort","volume":"21","author":"Vavricka","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/ecco-jcc\/jjy191","article-title":"The pathogenesis of extraintestinal manifestations: Implications for IBD research, diagnosis, and therapy","volume":"13","author":"Hedin","year":"2019","journal-title":"J. Crohns Colitis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/apt.12794","article-title":"Systematic review: The epidemiology of the hepatobiliary manifestations in patients with inflammatory bowel disease","volume":"40","author":"Gizard","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pouwels, S., Sakran, N., Graham, Y., Leal, A., Pintar, T., Yang, W., Kassir, R., Singhal, R., Mahawar, K., and Ramnarain, D. (2022). Non-alcoholic fatty liver disease (NAFLD): A review of pathophysiology, clinical management and effects of weight loss. BMC Endocr. Disord., 22.","DOI":"10.1186\/s12902-022-00980-1"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Berardo, C., Di Pasqua, L.G., Cagna, M., Richelmi, P., Vairetti, M., and Ferrigno, A. (2020). Nonalcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis: Current Issues and Future Perspectives in Preclinical and Clinical Research. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249646"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1097\/MEG.0000000000002607","article-title":"The impact of nonalcoholic fatty liver disease on inflammatory bowel disease-related hospitalization outcomes: A systematic review","volume":"35","author":"Boustany","year":"2023","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hyun, H.K., Lee, H.W., Park, J., Park, S.J., Park, J.J., Kim, T.I., Lee, J.S., Kim, B.K., Park, J.Y., and Kim, D.Y. (2023). Hepatic Steatosis but Not Fibrosis Is Independently Associated with Poor Outcomes in Patients with Inflammatory Bowel Disease. Gut Liver, 18, online first.","DOI":"10.5009\/gnl220409"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1093\/ecco-jcc\/jjab212","article-title":"Inflammatory Bowel Disease-associated Fatty Liver Disease: The Potential Effect of Biologic Agents","volume":"16","author":"Papaefthymiou","year":"2021","journal-title":"J. Crohns Colitis"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17","DOI":"10.7570\/jomes22021","article-title":"Recent Epidemiology and Risk Factors of Nonalcoholic Fatty Liver Disease","volume":"31","author":"Huh","year":"2022","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1053\/j.gastro.2020.01.052","article-title":"Nonalcoholic Fatty Liver Disease 2020: The State of the Disease","volume":"158","author":"Cotter","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.humpath.2017.09.008","article-title":"Primary sclerosing cholangitis is protective against nonalcoholic fatty liver disease in inflammatory bowel disease","volume":"69","author":"Bosch","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_16","first-page":"54","article-title":"Liver biopsy in inflammatory bowel disease patients with sustained abnormal liver function tests: A retrospective single-center study","volume":"36","author":"Dias","year":"2023","journal-title":"Ann. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7367","DOI":"10.3748\/wjg.v26.i46.7367","article-title":"Prevalence and risk factors of nonalcoholic fatty liver disease in patients with inflammatory bowel diseases: A cross-sectional and longitudinal analysis","volume":"26","author":"Hoffmann","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.1007\/s10620-020-06588-6","article-title":"Nonalcoholic Fatty Liver Disease Is Common in IBD Patients However Progression to Hepatic Fibrosis by Noninvasive Markers Is Rare","volume":"66","author":"Ritaccio","year":"2020","journal-title":"Dig. Dis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Adams, L.C., L\u00fcbbe, F., Bressem, K., Wagner, M., Hamm, B., and Makowski, M.R. (2018). Non-alcoholic fatty liver disease in underweight patients with inflammatory bowel disease: A case-control study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0206450"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1093\/ibd\/izy200","article-title":"Screening for Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Diseases: A Cohort Study Using Transient Elastography","volume":"25","author":"Palumbo","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_21","first-page":"463","article-title":"High prevalence of non-alcoholic fatty liver disease in patients with inflammatory bowel disease receiving anti-tumor necrosis factor therapy","volume":"32","author":"Likhitsup","year":"2019","journal-title":"Ann. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19954","DOI":"10.1038\/s41598-021-98843-7","article-title":"Hepatobiliary phenotype of individuals with chronic intestinal disorders","volume":"11","author":"Voss","year":"2021","journal-title":"Sci Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1093\/ibd\/izaa189","article-title":"Prevalence of Nonalcoholic Fatty Liver Disease in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis","volume":"27","author":"Lin","year":"2020","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Navarro, P., Guti\u00e9rrez-Ram\u00edrez, L., Tejera-Mu\u00f1oz, A., Arias, \u00c1., and Lucendo, A.J. (2023). Systematic Review and Meta-Analysis: Prevalence of Non-Alcoholic Fatty Liver Disease and Liver Fibrosis in Patients with Inflammatory Bowel Disease. Nutrients, 15.","DOI":"10.3390\/nu15214507"},{"key":"ref_25","first-page":"406","article-title":"Increased risk of MAFLD and Liver Fibrosis in Inflammatory Bowel Disease Independent of Classic Metabolic Risk Factors","volume":"21","author":"Calleja","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1007\/s10620-022-07562-0","article-title":"Crohn\u2019s Disease Is Associated with Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease","volume":"68","author":"Aggarwal","year":"2022","journal-title":"Dig. Dis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Dom\u00ednguez, S.J., Garc\u00eda-Mateo, S., Laredo, V., Gargallo-Puyuelo, C.J., Llera, B.G., de la Cruz, J.L., and Gomoll\u00f3n, F. (2023). Liver Fibrosis in Non-Alcoholic Fatty Liver Disease and Progression to Hepatocellular Carcinoma in Patients with Inflammatory Bowel Disease: A Systematic Review. Cancers, 15.","DOI":"10.3390\/cancers15133367"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3748\/wjg.v20.i1.91","article-title":"Inflammatory bowel disease: Pathogenesis","volume":"20","author":"Zhang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.thromres.2023.11.005","article-title":"Gut dysbiosis-related thrombosis in inflammatory bowel disease: Potential disease mechanisms and emerging therapeutic strategies","volume":"232","author":"Papa","year":"2023","journal-title":"Thromb. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Saez, A., Herrero-Fernandez, B., Gomez-Bris, R., S\u00e1nchez-Martinez, H., and Gonzalez-Granado, J.M. (2023). Pathophysiology of Inflammatory Bowel Disease: Innate Immune System. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021526"},{"key":"ref_31","first-page":"3178","article-title":"Innate and adaptive immunity in inflammatory bowel disease","volume":"17","author":"Siegmund","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","article-title":"Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease","volume":"75","author":"Ipsen","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Syed-Abdul, M.M. (2023). Lipid Metabolism in Metabolic-Associated Steatotic Liver Disease (MASLD). Metabolites, 14.","DOI":"10.3390\/metabo14010012"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Dixon, E.D., Nardo, A.D., Claudel, T., and Trauner, M. (2021). The Role of Lipid Sensing Nuclear Receptors (PPARs and LXR) and Metabolic Lipases in Obesity, Diabetes and NAFLD. Genes, 12.","DOI":"10.3390\/genes12050645"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1093\/ibd\/izz043","article-title":"Systematic Review with Meta-analysis: Epidemiology of Nonalcoholic Fatty Liver Disease in Patients with Inflammatory Bowel Disease","volume":"25","author":"Zou","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1097\/MIB.0000000000001085","article-title":"Epidemiology and Risk Factors of Nonalcoholic Fatty Liver Disease Among Patients with Inflammatory Bowel Disease","volume":"23","author":"Glassner","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"van Schaik, F.D.M., Gadaleta, R.M., Schaap, F.G., van Mil, S.W.C., Siersema, P.D., Oldenburg, B., and van Erpecum, K.J. (2012). Pharmacological Activation of the Bile Acid Nuclear Farnesoid X Receptor Is Feasible in Patients with Quiescent Crohn\u2019s Colitis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049706"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1097\/MIB.0000000000000832","article-title":"Incidence and Predictors of Nonalcoholic Fatty Liver Disease by Serum Biomarkers in Patients with Inflammatory Bowel Disease","volume":"22","author":"Bessissow","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5676","DOI":"10.3748\/wjg.v25.i37.5676","article-title":"Nonalcoholic fatty liver disease in patients with inflammatory bowel disease: Beyond the natural history","volume":"25","author":"Paduano","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.cgh.2020.07.067","article-title":"Accuracy of Ultrasound for Evaluation of Colorectal Segments in Patients with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis","volume":"19","author":"Sagami","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1093\/ibd\/izy051","article-title":"Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors","volume":"24","author":"Principi","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.jhep.2017.05.007","article-title":"Targeting the gut-liver axis in liver disease","volume":"67","author":"Wiest","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1016\/S0140-6736(19)33041-7","article-title":"Obeticholic acid for the treatment of non-alcoholic steatohepatitis: Interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial","volume":"394","author":"Younossi","year":"2019","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.surg.2016.07.018","article-title":"Liver steatosis induced by small bowel resection is prevented by oral vancomycin","volume":"160","author":"Barron","year":"2016","journal-title":"Surgery"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1124\/pr.108.000604","article-title":"The Role of Incretins in Glucose Homeostasis and Diabetes Treatment","volume":"60","author":"Kim","year":"2008","journal-title":"Pharmacol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1016\/j.jpedsurg.2005.05.045","article-title":"The route of lipid administration affects parenteral nutrition\u2013induced hepatic steatosis in a mouse model","volume":"40","author":"Javid","year":"2005","journal-title":"J. Pediatr. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S1534-5807(02)00187-9","article-title":"Redundant Pathways for Negative Feedback Regulation of Bile Acid Production","volume":"2","author":"Wang","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/ncp.10461","article-title":"Mechanisms of Parenteral Nutrition\u2013Associated Liver and Gut Injury","volume":"35","author":"Madnawat","year":"2019","journal-title":"Nutr. Clin. Pract."},{"key":"ref_49","first-page":"Doc17","article-title":"Complications and monitoring\u2014Guidelines on Parenteral Nutrition, Chapter 11","volume":"7","author":"Hartl","year":"2009","journal-title":"Ger. Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1177\/0148607193017004301","article-title":"Liver Dysfunction and Energy Source: Results of a Randomized Clinical Trial","volume":"17","author":"Buchmiller","year":"1993","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/ncp.10830","article-title":"Beyond lipids: Novel mechanisms for parenteral nutrition\u2013associated liver disease","volume":"37","author":"Wichman","year":"2022","journal-title":"Nutr. Clin. Pract."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.jcmgh.2022.05.008","article-title":"Liver PP2A-C\u03b1 Protects From Parenteral Nutrition-associated Hepatic Steatosis","volume":"14","author":"Maitiabula","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Denton, C., Price, A., Friend, J., Manithody, C., Blomenkamp, K., Westrich, M., Kakarla, V., Phillips, W., Krebs, J., and Abraham, A.S.M. (2018). Role of the Gut-Liver Axis in Driving Parenteral Nutrition-Associated Injury. Children, 5.","DOI":"10.3390\/children5100136"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1210\/endo.143.5.8850","article-title":"Transgenic Mice Expressing Human Fibroblast Growth Factor-19 Display Increased Metabolic Rate and Decreased Adiposity","volume":"143","author":"Tomlinson","year":"2002","journal-title":"Endocrinology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S1097-2765(00)00050-2","article-title":"Molecular Basis for Feedback Regulation of Bile Acid Synthesis by Nuclear Receptors","volume":"6","author":"Lu","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1194\/jlr.D200043-JLR200","article-title":"Monitoring hepatic cholesterol 7\u03b1-hydroxylase activity by assay of the stable bile acid intermediate 7\u03b1-hydroxy-4-cholesten-3-one in peripheral blood","volume":"44","author":"Arvidsson","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_57","first-page":"G218","article-title":"Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs","volume":"302","author":"Jain","year":"2012","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1177\/0148607116661838","article-title":"Preserved Gut Microbial Diversity Accompanies Upregulation of TGR5 and Hepatobiliary Transporters in Bile Acid\u2013Treated Animals Receiving Parenteral Nutrition","volume":"41","author":"Jain","year":"2016","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5630","DOI":"10.3748\/wjg.14.5630","article-title":"Intestinal bile acid physiology and pathophysiology","volume":"14","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.2174\/0929867321666140303142053","article-title":"Metabolic Effects of Bile Acids in the Gut in Health and Disease","volume":"21","author":"Boesjes","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cerd\u00f3, T., Garc\u00eda-Santos, J.A., Rodr\u00edguez-P\u00f6hnlein, A., Garc\u00eda-Ricobaraza, M., Nieto-Ru\u00edz, A., Berm\u00fadez, M.G., and Campoy, C. (2022). Impact of Total Parenteral Nutrition on Gut Microbiota in Pediatric Population Suffering Intestinal Disorders. Nutrients, 14.","DOI":"10.3390\/nu14214691"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5832","DOI":"10.1128\/IAI.72.10.5832-5839.2004","article-title":"Bacteroides fragilis Enterotoxin Induces Intestinal Epithelial Cell Secretion of Interleukin-8 through Mitogen-Activated Protein Kinases and a Tyrosine Kinase-Regulated Nuclear Factor-\u03baB Pathway","volume":"72","author":"Wu","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14979","DOI":"10.1073\/pnas.95.25.14979","article-title":"Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin","volume":"95","author":"Wu","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Remacle, A.G., Shiryaev, S.A., and Strongin, A.Y. (2014). Distinct Interactions with Cellular E-Cadherin of the Two Virulent Metalloproteinases Encoded by a Bacteroides fragilis Pathogenicity Island. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113896"},{"key":"ref_65","first-page":"1273","article-title":"Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis*1, *2","volume":"22","author":"Whiting","year":"1995","journal-title":"J. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"G567","DOI":"10.1152\/ajpgi.00232.2007","article-title":"LPS induces the TNF-alpha-mediated downregulation of rat liver aquaporin-8: Role in sepsis-associated cholestasis","volume":"294","author":"Lehmann","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_67","first-page":"570","article-title":"Microbiota and inflammatory bowel disease: An update","volume":"109","author":"Talocco","year":"2018","journal-title":"Recent. Prog. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e63642","DOI":"10.7554\/eLife.63642","article-title":"Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease","volume":"10","author":"Liu","year":"2021","journal-title":"eLife"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/ame2.12255","article-title":"Association between intestinal microbiota and inflammatory bowel disease","volume":"5","author":"Zhang","year":"2022","journal-title":"Anim. Model. Exp. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrgastro.2017.88","article-title":"Gut microbiota and IBD: Causation or correlation?","volume":"14","author":"Ni","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1002\/hep.22848","article-title":"Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease","volume":"49","author":"Miele","year":"2009","journal-title":"Hepatology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/hep.30036","article-title":"Hepatocellular Carcinoma Is Associated with Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease","volume":"69","author":"Ponziani","year":"2019","journal-title":"Hepatology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/gutjnl-2019-319664","article-title":"Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites","volume":"70","author":"Zhang","year":"2020","journal-title":"Gut"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mai, H., Yang, X., Xie, Y., Zhou, J., Wang, Q., Wei, Y., Yang, Y., Lu, D., Ye, L., and Cui, P. (2024). The role of gut microbiota in the occurrence and progression of non-alcoholic fatty liver disease. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1257903"},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"5283","DOI":"10.1038\/s41598-021-84761-1","article-title":"DSS-induced colitis is associated with adipose tissue dysfunction and disrupted hepatic lipid metabolism leading to hepatosteatosis and dyslipidemia in mice","volume":"11","author":"Kwon","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/ibd.21669","article-title":"Changing shape of disease: Nonalcoholic fatty liver disease in Crohn\u2019s disease\u2014A case series and review of the literature","volume":"18","author":"McGowan","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1097\/MEG.0000000000001144","article-title":"Effects of inflammatory bowel disease treatment on the risk of nonalcoholic fatty liver disease: A meta-analysis","volume":"30","author":"Lapumnuaypol","year":"2018","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/ecco-jcc\/jjab178","article-title":"ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment","volume":"16","author":"Raine","year":"2021","journal-title":"J. Crohns Colitis"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/ecco-jcc\/jjz180","article-title":"ECCO Guidelines on Therapeutics in Crohn\u2019s Disease: Medical Treatment","volume":"14","author":"Torres","year":"2019","journal-title":"J. Crohns Colitis"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.2147\/DMSO.S247379","article-title":"Glucocorticoid-Induced Fatty Liver Disease","volume":"13","author":"Rahimi","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1097\/MCG.0000000000001727","article-title":"Steroid Use and Risk of Nonalcoholic Fatty Liver Disease in Patients with Inflammatory Bowel Disease","volume":"57","author":"Trivedi","year":"2022","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e279","DOI":"10.1016\/j.crohns.2012.10.015","article-title":"Risk factors of non-alcoholic fatty liver disease in patients with inflammatory bowel disease","volume":"7","author":"Sourianarayanane","year":"2013","journal-title":"J. Crohns Colitis"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7727","DOI":"10.3748\/wjg.v22.i34.7727","article-title":"Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article","volume":"22","author":"Chao","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/1751-2980.12184","article-title":"A review of methotrexate-associated hepatotoxicity","volume":"15","author":"Bath","year":"2014","journal-title":"J. Dig. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.4254\/wjh.v13.i12.1956","article-title":"Liver manifestations and complications in inflammatory bowel disease: A review","volume":"13","author":"Gaspar","year":"2021","journal-title":"World J. Hepatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jhep.2022.12.034","article-title":"Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated","volume":"78","author":"Atallah","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1111\/jgh.15631","article-title":"Circulating tumor necrosis factor-\u03b1 levels in non-alcoholic fatty liver disease: A systematic review and a meta-analysis","volume":"36","author":"Potoupni","year":"2021","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_89","first-page":"127","article-title":"The multi-hit process and the antagonistic roles of tumor necrosis factor-alpha and adiponectin in non alcoholic fatty liver disease","volume":"13","author":"Polyzos","year":"2009","journal-title":"Hippokratia"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1136\/gut.2004.046516","article-title":"Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn\u2019s disease","volume":"54","author":"Yamamoto","year":"2005","journal-title":"Gut"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/MIB.0000000000000209","article-title":"Metabolic Inflammation in Inflammatory Bowel Disease","volume":"21","author":"Magro","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Yen, H.-H., Su, P.-Y., Huang, S.-P., Wu, L., Hsu, T.-C., Zeng, Y.-H., and Chen, Y.-Y. (2021). Evaluation of non-alcoholic fatty liver disease in patients with inflammatory bowel disease using controlled attenuation parameter technology: A Taiwanese retrospective cohort study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252286"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1097\/MCG.0b013e3181ec5c66","article-title":"The Potential Adverse Role of Leptin Resistance in Nonalcoholic Fatty Liver Disease","volume":"45","author":"Polyzos","year":"2011","journal-title":"J. Clin. Gastroenterol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3278\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:13:20Z","timestamp":1760105600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,14]]},"references-count":93,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25063278"],"URL":"https:\/\/doi.org\/10.3390\/ijms25063278","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,14]]}}}