Bandyopadhyay S, Samajdar SS, Mukherjee S, Joshi SR. Bile acid receptor signaling in metabolic dysfunction-associated steatotic liver disease: Mechanistic insights and emerging therapeutic strategies. World J Hepatol 2026; 18(6): 118548 [DOI: 10.4254/wjh.118548]
Corresponding Author of This Article
Sanjay Bandyopadhyay, DM, FRCP, Senior Consultant, Department of Gastroenterology, ILS Dumdum Hospital, 1 Mall Road, Kolkata 700080, West Bengal, India. drsanjaygastro@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
review-article
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Jun 27, 2026; 18(6): 118548 Published online Jun 27, 2026. doi: 10.4254/wjh.118548
Bile acid receptor signaling in metabolic dysfunction-associated steatotic liver disease: Mechanistic insights and emerging therapeutic strategies
Sanjay Bandyopadhyay, Shambo Samrat Samajdar, Shatavisa Mukherjee, Shashank R Joshi
Sanjay Bandyopadhyay, Department of Gastroenterology, ILS Dumdum Hospital, Kolkata 700080, West Bengal, India
Shambo Samrat Samajdar, Department of Out-Patient Affiliation, Diabetes and Allergy-Asthma Therapeutic Specialty Clinic, Kolkata 700059, West Bengal, India
Shatavisa Mukherjee, Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata 700073, West Bengal, India
Shashank R Joshi, Department of Diabetology and Endocrinology, Lilavati Hospital and Research Centre, Mumbai 400050, Maharasthra, India
Author contributions: Bandyopadhyay S and Joshi SR contributed to the conceptualization and overall design of the study, provided senior academic and clinical oversight, and critically revised the manuscript for important intellectual content; Samajdar SS and Mukherjee S were responsible for the literature review, methodological planning, data synthesis and interpretation, and drafting of the manuscript. All authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Sanjay Bandyopadhyay, DM, FRCP, Senior Consultant, Department of Gastroenterology, ILS Dumdum Hospital, 1 Mall Road, Kolkata 700080, West Bengal, India. drsanjaygastro@gmail.com
Received: January 5, 2026 Revised: February 10, 2026 Accepted: April 3, 2026 Published online: June 27, 2026 Processing time: 165 Days and 11.3 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, spanning a spectrum from simple steatosis to metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. In addition to liver-related morbidity, MASLD is closely associated with systemic metabolic dysfunction and increased cardiovascular risk, emphasizing the need for mechanism-based therapies. Bile acids are now recognized as key metabolic and immunological signaling molecules acting through receptors such as the farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor Takeda G-protein-coupled receptor 5. This narrative review summarizes current evidence on bile acid receptor signaling in MASLD, focusing on receptor biology, molecular mechanisms, and emerging therapeutic strategies. We discuss how changes in bile acid composition, receptor responsiveness, and downstream signaling contribute to metabolic dysregulation, inflammation, and fibrogenesis, while acknowledging inter-individual heterogeneity and limited stage-specific human data. Particular attention is given to FXR and Takeda G-protein-coupled receptor 5 signaling, their interaction with metabolic and inflammatory pathways, and modulation by gut microbiota-derived bile acid transformations. We also review clinical and translational data on bile acid-targeted therapies, including FXR agonists and norursodeoxycholic acid, highlighting therapeutic promise alongside challenges related to lipid effects, long-term safety, and variable efficacy. Overall, bile acid signaling represents a promising yet complex therapeutic axis in MASLD.
Core Tip: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a global health challenge with limited pharmacological options. This review highlights the emerging role of bile acid receptors - particularly farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 - as therapeutic targets in MASLD. It synthesizes recent advances in receptor signaling, gut microbiota-bile acid interactions, and the development of FXR agonists, norursodeoxycholic acid, and dual FXR/Takeda G-protein-coupled receptor 5 agents. The review also outlines future directions in precision hepatology, proposing receptor-specific, microbiome-informed strategies for managing MASLD.
