Abdalla MMI. Gut-liver axis in diabetes: Mechanisms and therapeutic opportunities. World J Gastroenterol 2025; 31(29): 109090 [PMID: 40809928 DOI: 10.3748/wjg.v31.i29.109090]
Corresponding Author of This Article
Mona Mohamed Ibrahim Abdalla, MD, PhD, Department of Human Biology, School of Medicine, International Medical University, No. 126 Jln Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, Malaysia. monamohamed@imu.edu.my
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
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 Gastroenterol. Aug 7, 2025; 31(29): 109090 Published online Aug 7, 2025. doi: 10.3748/wjg.v31.i29.109090
Gut-liver axis in diabetes: Mechanisms and therapeutic opportunities
Mona Mohamed Ibrahim Abdalla
Mona Mohamed Ibrahim Abdalla, Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
Author contributions: Abdalla MMI performed the research and wrote the paper.
Conflict-of-interest statement: The author has no conflict of interest to declare.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mona Mohamed Ibrahim Abdalla, MD, PhD, Department of Human Biology, School of Medicine, International Medical University, No. 126 Jln Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, Malaysia. monamohamed@imu.edu.my
Received: April 29, 2025 Revised: June 3, 2025 Accepted: July 8, 2025 Published online: August 7, 2025 Processing time: 98 Days and 15.1 Hours
Abstract
The gut-liver axis represents a complex, bidirectional communication network between the gastrointestinal tract and the liver, playing a central role in maintaining metabolic homeostasis. In diabetes, disruption of this axis, mediated by gut microbiota dysbiosis, impaired intestinal barrier function, and pro-inflammatory signaling, contributes significantly to insulin resistance, hepatic steatosis, and systemic metabolic dysfunction. This review explores the underlying mechanisms by which microbial alterations, increased gut permeability, and inflammatory pathways influence hepatic insulin resistance and glucose metabolism. In addition to established mechanisms, emerging pathways involving neuroendocrine circuits, microbial metabolites, and immune mediators are discussed, offering deeper insight into gut-liver interactions in metabolic disease. The review also outlines therapeutic strategies targeting the gut-liver axis, including microbiota modulation, barrier function enhancement, and anti-inflammatory interventions, emphasizing their potential in advancing diabetes management. A conceptual framework is proposed to integrate these components into a precision medicine approach for metabolic regulation. Key challenges in clinical translation, including patient heterogeneity and the absence of reliable biomarkers to guide treatment decisions are also discussed to inform future research. By linking mechanistic understanding with therapeutic innovation, the review highlights the gut-liver axis as a promising target for personalized diabetes care.
Core Tip: Disruption of the gut-liver axis plays a critical role in the pathophysiology of diabetes by linking gut microbiota alterations, intestinal barrier dysfunction, and inflammatory pathways to hepatic insulin resistance and impaired glucose metabolism. Understanding these mechanisms opens new therapeutic opportunities, including microbiota modulation, gut barrier reinforcement, and targeted anti-inflammatory strategies. These approaches have the potential to significantly improve diabetes management and metabolic outcomes.
