{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:56:51Z","timestamp":1794049011912,"version":"4.8.0"},"reference-count":107,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive bile duct inflammation and fibrosis. Its strong association with inflammatory bowel disease (IBD) highlights the possible role of the gut\u2013liver axis in disease pathogenesis. Here, we review the mechanisms that may contribute to the disruption of the gut\u2013liver axis, leading to liver injury and the development of PSC. In particular, disruption of the intestinal barrier allows microbial products to enter the portal circulation, stimulating hepatic immune cells and triggering biliary inflammation. Concurrently, gut-primed lymphocytes expressing mucosal homing receptors migrate aberrantly to the liver, where they may contribute to biliary epithelial cell injury. Dysbiosis, characterized by reduced microbial diversity and the expansion of bile-tolerant and pro-inflammatory taxa, amplifies this immune activation and disturbs gut\u2013liver homeostasis. Moreover, bile acids act as signaling molecules, regulating metabolism and immune responses through receptors such as FXR and TGR5. Dysregulation of these pathways may promote cholestasis, inflammation, and fibrosis. By understanding these interactions, we may identify novel therapeutic targets for PSC.<\/jats:p>","DOI":"10.3390\/jcm14217817","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T19:30:27Z","timestamp":1762198227000},"page":"7817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Gut\u2013Liver Axis, Microbiota, Bile Acids, and Immune Response in Pathogenesis of Primary Sclerosing Cholangitis: An Overview"],"prefix":"10.3390","volume":"14","author":[{"given":"Fotios S.","family":"Fousekis","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Mpakogiannis","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6106-8178","authenticated-orcid":false,"given":"Georgios D.","family":"Lianos","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-9047","authenticated-orcid":false,"given":"Elisabetta","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hepatology and Digestive Endoscopy Section, Department of Medicine and Surgery, University of Perugia Medical School, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-1812","authenticated-orcid":false,"given":"Gabrio","family":"Bassotti","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hepatology and Digestive Endoscopy Section, Department of Medicine and Surgery, University of Perugia Medical School, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos H.","family":"Katsanos","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1016\/S0140-6736(18)30300-3","article-title":"Primary sclerosing cholangitis","volume":"391","author":"Dyson","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1148\/radiol.10091953","article-title":"Primary sclerosing cholangitis: Meta-analysis of diagnostic performance of MR cholangiopancreatography","volume":"256","author":"Dave","year":"2010","journal-title":"Radiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/hep.32771","article-title":"AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma","volume":"77","author":"Bowlus","year":"2023","journal-title":"Hepatology."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1053\/jhep.2002.33202","article-title":"Small-duct primary sclerosing cholangitis: A long-term follow-up study","volume":"35","author":"Angulo","year":"2002","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1053\/j.gastro.2008.01.042","article-title":"The natural history of small-duct primary sclerosing cholangitis","volume":"134","author":"Bjornsson","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1136\/gut.38.4.610","article-title":"Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis","volume":"38","author":"Broome","year":"1996","journal-title":"Gut"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/hep.26454","article-title":"Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in Utah children: Epidemiology and natural history","volume":"58","author":"Deneau","year":"2013","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2022). EASL Clinical Practice Guidelines on sclerosing cholangitis. J. Hepatol., 77, 761\u2013806.","DOI":"10.1016\/j.jhep.2022.05.011"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11729","DOI":"10.3389\/ti.2023.11729","article-title":"Liver Transplantation for Primary Sclerosing Cholangitis (PSC) With or Without Inflammatory Bowel Disease (IBD)\u2014A European Society of Organ Transplantation (ESOT) Consensus Statement","volume":"36","author":"Carbone","year":"2023","journal-title":"Transpl. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41572-025-00600-x","article-title":"Primary sclerosing cholangitis","volume":"11","author":"Manns","year":"2025","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1053\/j.gastro.2021.08.032","article-title":"Prevalence of Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis","volume":"161","author":"Barberio","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S209","DOI":"10.1093\/ecco-jcc\/jjx180.344","article-title":"P217 Usefulness of systematic liver biopsy during a surgery for inflammatory bowel disease for the diagnosis of primary sclerosing cholangitis","volume":"12","author":"Miard","year":"2018","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jhep.2023.09.031","article-title":"Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two?","volume":"80","author":"Bergquist","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/MEG.0000000000000576","article-title":"Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: A meta-analysis of 16 observational studies","volume":"28","author":"Zheng","year":"2016","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/S0140-6736(02)11861-7","article-title":"Risk factors for recurrence of primary sclerosing cholangitis of liver allograft","volume":"360","author":"Vera","year":"2002","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/lt.21679","article-title":"A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts","volume":"15","author":"Alabraba","year":"2009","journal-title":"Liver Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: Pathophysiological basis for therapy","volume":"72","author":"Albillos","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41575-022-00690-y","article-title":"The microbiota and the gut-liver axis in primary sclerosing cholangitis","volume":"20","author":"Hov","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Blesl, A., and Stadlbauer, V. (2021). The Gut-Liver Axis in Cholestatic Liver Diseases. Nutrients, 13.","DOI":"10.3390\/nu13031018"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kobayashi, T., Iwaki, M., Nakajima, A., Nogami, A., and Yoneda, M. (2022). Current Research on the Pathogenesis of NAFLD\/NASH and the Gut-Liver Axis: Gut Microbiota, Dysbiosis, and Leaky-Gut Syndrome. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911689"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1136\/gutjnl-2019-318427","article-title":"Leaky gut: Mechanisms, measurement and clinical implications in humans","volume":"68","author":"Camilleri","year":"2019","journal-title":"Gut"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1097\/MOG.0000000000000243","article-title":"Leaky gut\u2014Concept or clinical entity?","volume":"32","author":"Quigley","year":"2016","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrgastro.2016.169","article-title":"The intestinal epithelial barrier: A therapeutic target?","volume":"14","author":"Odenwald","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1002\/hep.31311","article-title":"The Role of the Intestine in the Pathogenesis of Primary Sclerosing Cholangitis: Evidence and Therapeutic Implications","volume":"72","author":"Dean","year":"2020","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bozward, A.G., Ronca, V., Osei-Bordom, D., and Oo, Y.H. (2021). Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.711217"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-immunol-080719-015428","article-title":"MAIT Cells in Health and Disease","volume":"38","author":"Provine","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nature11605","article-title":"MR1 presents microbial vitamin B metabolites to MAIT cells","volume":"491","author":"Patel","year":"2012","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.1800455","article-title":"Bidirectional Cross-Talk between Biliary Epithelium and Th17 Cells Promotes Local Th17 Expansion and Bile Duct Proliferation in Biliary Liver Diseases","volume":"203","author":"Jeffery","year":"2019","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1053\/j.gastro.2024.06.032","article-title":"Gut Pathobiont-Derived Outer Membrane Vesicles Drive Liver Inflammation and Fibrosis in Primary Sclerosing Cholangitis-Associated Inflammatory Bowel Disease","volume":"167","author":"Dorner","year":"2024","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Losa, M., Schwarzfischer, M., Emmenegger, M., Spalinger, M.R., Rogler, G., and Scharl, M. (2025). Unraveling the Converging Roles of ASC-Dependent Inflammasomes, Interleukin-1 Superfamily Members, Serum Amyloid A, and Non-Sterile Inflammation in Disease Pathology and Fibrosis in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26168042"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1113\/jphysiol.2011.219691","article-title":"Role of innate immunity and the microbiota in liver fibrosis: Crosstalk between the liver and gut","volume":"590","author":"Seki","year":"2012","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1002\/eji.201847608","article-title":"Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells","volume":"48","author":"Zimmer","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"113175","DOI":"10.1016\/j.intimp.2024.113175","article-title":"Dysregulation and impaired anti-bacterial potential of mucosal-associated invariant T cells in autoimmune liver diseases","volume":"142 Pt B","author":"Wang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/liv.13979","article-title":"Circulating markers of gut barrier function associated with disease severity in primary sclerosing cholangitis","volume":"39","author":"Dhillon","year":"2019","journal-title":"Liver Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2147\/CEG.S508794","article-title":"Serological Markers of Intestinal Barrier Function and Inflammation as Potential Predictors of Recurrent Primary Sclerosing Cholangitis","volume":"18","author":"Hlavaty","year":"2025","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41564-018-0333-1","article-title":"Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis","volume":"4","author":"Nakamoto","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1038\/s41467-023-39029-9","article-title":"Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis","volume":"14","author":"Ichikawa","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5412","DOI":"10.3748\/wjg.v23.i29.5412","article-title":"Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis","volume":"23","author":"Tornai","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Giordano, D.M., Pinto, C., Maroni, L., Benedetti, A., and Marzioni, M. (2018). Inflammation and the Gut-Liver Axis in the Pathophysiology of Cholangiopathies. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103003"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/BF02365447","article-title":"Small duct cholangitis induced by N-formyl L-methionine L-leucine L-tyrosine in rats","volume":"29","author":"Yamada","year":"1994","journal-title":"J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1478-3231.1999.tb00043.x","article-title":"Macrophages are essential for lymphocyte infiltration in formyl peptide-induced cholangitis in rat liver","volume":"19","author":"Yamada","year":"1999","journal-title":"Liver"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.jhep.2016.09.020","article-title":"The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation","volume":"66","author":"Schrumpf","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nri1222","article-title":"Homing and cellular traffic in lymph nodes","volume":"3","author":"Mempel","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.immuni.2004.08.011","article-title":"Retinoic acid imprints gut-homing specificity on T cells","volume":"21","author":"Iwata","year":"2004","journal-title":"Immunity"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1089\/jir.2016.0076","article-title":"Mucosal Chemokines","volume":"37","author":"Zlotnik","year":"2017","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5069","DOI":"10.4049\/jimmunol.165.9.5069","article-title":"The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system","volume":"165","author":"Papadakis","year":"2000","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.jhep.2019.05.006","article-title":"Return to sender: Lymphocyte trafficking mechanisms as contributors to primary sclerosing cholangitis","volume":"71","author":"Wildenberg","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s00281-014-0439-3","article-title":"Mechanisms of tissue injury in autoimmune liver diseases","volume":"36","author":"Liaskou","year":"2014","journal-title":"Semin. Immunopathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jhep.2016.09.016","article-title":"Bad memories from the gut may cause nightmares for the bile ducts","volume":"66","author":"Fickert","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/cmi.2016.4","article-title":"Adaptive immunity in the liver","volume":"13","author":"Shuai","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/hep.26702","article-title":"CD8 T cells primed in the gut-associated lymphoid tissue induce immune-mediated cholangitis in mice","volume":"59","author":"Seidel","year":"2014","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1084\/jem.20041035","article-title":"Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis","volume":"200","author":"Eksteen","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jhep.2016.09.002","article-title":"Gut and liver T-cells of common clonal origin in primary sclerosing cholangitis-inflammatory bowel disease","volume":"66","author":"Henriksen","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"100054","DOI":"10.1016\/j.jtauto.2020.100054","article-title":"Characterization of gut-homing molecules in non-endstage livers of patients with primary sclerosing cholangitis and inflammatory bowel disease","volume":"3","author":"Visseren","year":"2020","journal-title":"J. Transl. Autoimmun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/hep.32193","article-title":"Aberrant hepatic trafficking of gut-derived T cells is not specific to primary sclerosing cholangitis","volume":"75","author":"Graham","year":"2022","journal-title":"Hepatology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/cmi.2018.7","article-title":"The microbiome and autoimmunity: A paradigm from the gut-liver axis","volume":"15","author":"Li","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1002\/hep4.1200","article-title":"Gut and Liver B Cells of Common Clonal Origin in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease","volume":"2","author":"Chung","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Su, X., Gao, Y., and Yang, R. (2023). Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1127743"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/j.2040-4603.2020.tb00108.x","article-title":"Intestinal Absorption of Bile Acids in Health and Disease","volume":"10","author":"Ticho","year":"2019","journal-title":"Compr. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Yan, W., Zhang, K., Guo, J., and Xu, L. (2025). Bile acid-mediated gut-liver axis crosstalk: The role of nuclear receptor signaling in dynamic regulation of inflammatory networks. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1595486"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1507\/endocrj.EJ22-0544","article-title":"The role of bile acids in regulating glucose and lipid metabolism","volume":"70","author":"Yu","year":"2023","journal-title":"Endocr. J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11055","DOI":"10.1074\/jbc.M117.784322","article-title":"Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism","volume":"292","author":"Pathak","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"111618","DOI":"10.1016\/j.mce.2022.111618","article-title":"Discovery of farnesoid X receptor and its role in bile acid metabolism","volume":"548","author":"Chiang","year":"2022","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"17545","DOI":"10.1021\/acs.jmedchem.1c01017","article-title":"Recent Advances in the Medicinal Chemistry of Farnesoid X Receptor","volume":"64","author":"Fang","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41575-020-00404-2","article-title":"The role of farnesoid X receptor in metabolic diseases, and gastrointestinal and liver cancer","volume":"18","author":"Sun","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Di Ciaula, A., Bonfrate, L., Baj, J., Khalil, M., Garruti, G., Stellaard, F., Wang, H.H., Wang, D.Q.-H., and Portincasa, P. (2022). Recent Advances in the Digestive, Metabolic and Therapeutic Effects of Farnesoid X Receptor and Fibroblast Growth Factor 19: From Cholesterol to Bile Acid Signaling. Nutrients, 14.","DOI":"10.3390\/nu14234950"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/hep.22519","article-title":"Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response","volume":"48","author":"Wang","year":"2008","journal-title":"Hepatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6251","DOI":"10.4049\/jimmunol.0803978","article-title":"The bile acid receptor FXR is a modulator of intestinal innate immunity","volume":"183","author":"Vavassori","year":"2009","journal-title":"J. Immunol."},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis","volume":"375","author":"Nevens","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"eabi4354","DOI":"10.1126\/scitranslmed.abi4354","article-title":"Farnesoid X receptor antagonizes macrophage-dependent licensing of effector T lymphocytes and progression of sclerosing cholangitis","volume":"14","author":"Shi","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"100874","DOI":"10.1016\/j.jhepr.2023.100874","article-title":"Non-steroidal FXR agonist cilofexor improves cholestatic liver injury in the Mdr2(-\/-) mouse model of sclerosing cholangitis","volume":"5","author":"Fuchs","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Milkiewicz, M., Klak, M., Kempinska-Podhorodecka, A., Wiechowska-Kozlowska, A., Urasinska, E., Blatkiewicz, M., Wunsch, E., Elias, E., and Milkiewicz, P. (2016). Impaired Hepatic Adaptation to Chronic Cholestasis induced by Primary Sclerosing Cholangitis. Sci. Rep., 6.","DOI":"10.1038\/srep39573"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/s12016-014-8443-x","article-title":"TGR5: Pathogenetic role and\/or therapeutic target in fibrosing cholangitis?","volume":"48","author":"Keitel","year":"2015","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s10020-024-00830-x","article-title":"The gut microbiota-bile acid axis in cholestatic liver disease","volume":"30","author":"Sun","year":"2024","journal-title":"Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jhep.2021.03.029","article-title":"Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis","volume":"75","author":"Reich","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/imm.12045","article-title":"TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn\u2019s disease","volume":"139","author":"Yoneno","year":"2013","journal-title":"Immunology"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Hov, J.R., Keitel, V., Laerdahl, J.K., Spomer, L., Ellinghaus, E., ElSharawy, A., Melum, E., Boberg, K.M., Manke, T., and Balschun, T. (2010). Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012403"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.autrev.2017.07.002","article-title":"Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases","volume":"16","author":"Li","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Oleszycka, E., O\u2019Brien, E.C., Freeley, M., Lavelle, E.C., and Long, A. (2023). Bile acids induce IL-1alpha and drive NLRP3 inflammasome-independent production of IL-1beta in murine dendritic cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1285357"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Kubota, H., Ishizawa, M., Kodama, M., Nagase, Y., Kato, S., Makishima, M., and Sakurai, K. (2023). Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043517"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1159\/000538493","article-title":"Gut Microbiota in Primary Sclerosing Cholangitis: From Prognostic Role to Therapeutic Implications","volume":"42","author":"Maccauro","year":"2024","journal-title":"Dig. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1136\/gutjnl-2020-323565","article-title":"Altered faecal microbiome and metabolome in IgG4-related sclerosing cholangitis and primary sclerosing cholangitis","volume":"71","author":"Liu","year":"2022","journal-title":"Gut"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Ozdirik, B., Muller, T., Wree, A., Tacke, F., and Sigal, M. (2021). The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136975"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1136\/gutjnl-2015-311004","article-title":"Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD","volume":"65","author":"Sabino","year":"2016","journal-title":"Gut"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1111\/apt.15375","article-title":"Consistent alterations in faecal microbiomes of patients with primary sclerosing cholangitis independent of associated colitis","volume":"50","author":"Ruhlemann","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/hep.32773","article-title":"A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation","volume":"77","author":"Hole","year":"2023","journal-title":"Hepatology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1053\/j.gastro.2020.12.058","article-title":"Altered Gut Microbial Metabolism of Essential Nutrients in Primary Sclerosing Cholangitis","volume":"160","author":"Kummen","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.3748\/wjg.v23.i25.4548","article-title":"Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis","volume":"23","author":"Bajer","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jcmgh.2023.12.005","article-title":"Microbial Players in Primary Sclerosing Cholangitis: Current Evidence and Concepts","volume":"17","author":"Ozdirik","year":"2024","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/jgh.12694","article-title":"Association between specific mucosa-associated microbiota in Crohn\u2019s disease at the time of resection and subsequent disease recurrence: A pilot study","volume":"30","author":"Kang","year":"2015","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1136\/gutjnl-2016-313332","article-title":"Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy","volume":"67","author":"Tang","year":"2018","journal-title":"Gut"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e70932","DOI":"10.1096\/fj.202403293RR","article-title":"Insights Into Intestinal Flora in Metabolic Dysfunction-Associated Steatotic Liver Disease","volume":"39","author":"Xin","year":"2025","journal-title":"FASEB J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1111\/apt.15754","article-title":"A disease-specific decline of the relative abundance of Bifidobacterium in patients with autoimmune hepatitis","volume":"51","author":"Liwinski","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1093\/ecco-jcc\/jjaa021","article-title":"A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease with Bile Acid Pathways","volume":"14","author":"Quraishi","year":"2020","journal-title":"J. Crohns Colitis."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Gasaly, N., Hermoso, M.A., and Gotteland, M. (2021). Butyrate and the Fine-Tuning of Colonic Homeostasis: Implication for Inflammatory Bowel Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063061"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11648","DOI":"10.1073\/pnas.1917597117","article-title":"Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin","volume":"117","author":"Wang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1046\/j.1365-2249.2003.02166.x","article-title":"Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases","volume":"132","author":"Muratori","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jhep.2009.01.023","article-title":"Influence of dominant bile duct stenoses and biliary infections on outcome in primary sclerosing cholangitis","volume":"51","author":"Rudolph","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1136\/gutjnl-2018-317791","article-title":"Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis","volume":"69","author":"Lemoinne","year":"2020","journal-title":"Gut"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1136\/gutjnl-2019-320008","article-title":"Gut mycobiome of primary sclerosing cholangitis patients is characterised by an increase of Trichocladium griseum and Candida species","volume":"69","author":"Ruhlemann","year":"2020","journal-title":"Gut"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.chom.2023.02.001","article-title":"Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease","volume":"31","author":"Zeng","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Zeng, S., and Schnabl, B. (2024). Gut mycobiome alterations and implications for liver diseases. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012377"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.jhep.2022.12.006","article-title":"Fungal infections and the fungal microbiome in hepatobiliary disorders","volume":"78","author":"Hartmann","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Meacci, D., Bruni, A., Cocquio, A., Dell\u2019Anna, G., Mandarino, F.V., Marasco, G., Cecinato, P., Barbara, G., and Zagari, R.M. (2025). Microbial Landscapes of the Gut-Biliary Axis: Implications for Benign and Malignant Biliary Tract Diseases. Microorganisms, 13.","DOI":"10.3390\/microorganisms13091980"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ali, A.H., Juran, B.D., Schlicht, E.M., Bianchi, J.K., McCauley, B.M., Atkinson, E.J., and Lazaridis, K.N. (2021). The PSC scientific community resource: An asset for multi-omics interrogation of primary sclerosing cholangitis. BMC Gastroenterol., 21.","DOI":"10.1186\/s12876-021-01930-2"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"814","DOI":"10.14309\/ajg.0000000000000604","article-title":"Targeting the Gut Microbiome as a Treatment for Primary Sclerosing Cholangitis: A Conceptional Framework","volume":"115","author":"Shah","year":"2020","journal-title":"Am. J. Gastroenterol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7817\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T19:56:52Z","timestamp":1762199812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":107,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14217817"],"URL":"https:\/\/doi.org\/10.3390\/jcm14217817","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]}}}