Akpoveta ED, Okpete UE, Byeon H. Unraveling the gut-liver axis in autoimmune liver disease overlap syndrome: A multi-omics perspective. World J Gastroenterol 2025; 31(37): 112298 [DOI: 10.3748/wjg.v31.i37.112298]
Corresponding Author of This Article
Haewon Byeon, PhD, Associate Professor, Worker’s Care and Digital Health Lab, Department of Future Technology, Korea University of Technology and Education, 1600, Chungjeol-ro, Cheonan 31253, Chungcheongnam-do, South Korea. bhwpuma@naver.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Letter to the Editor
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. Oct 7, 2025; 31(37): 112298 Published online Oct 7, 2025. doi: 10.3748/wjg.v31.i37.112298
Unraveling the gut-liver axis in autoimmune liver disease overlap syndrome: A multi-omics perspective
Eguono D Akpoveta, Uchenna E Okpete, Haewon Byeon
Eguono D Akpoveta, Department of Community Medicine, Federal Medical Centre, Asaba 322022, Delta state, Nigeria
Uchenna E Okpete, Department of Digital Anti-aging Healthcare (BK21), Inje University, Gimhae 50834, Gyeongsangnam-do, South Korea
Haewon Byeon, Worker’s Care and Digital Health Lab, Department of Future Technology, Korea University of Technology and Education, Cheonan 31253, Chungcheongnam-do, South Korea
Co-first authors: Eguono D Akpoveta and Uchenna E Okpete.
Author contributions: Akpoveta ED, Okpete UE and Byeon H contributed to this paper; Byeon H designed the study; Akpoveta ED and Okpete UE were involved in data interpretation, developed the methodology; Akpoveta ED, Okpete UE and Byeon H assisted in writing the article.
Supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, No. RS-2023-00237287.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Haewon Byeon, PhD, Associate Professor, Worker’s Care and Digital Health Lab, Department of Future Technology, Korea University of Technology and Education, 1600, Chungjeol-ro, Cheonan 31253, Chungcheongnam-do, South Korea. bhwpuma@naver.com
Received: July 23, 2025 Revised: August 23, 2025 Accepted: September 4, 2025 Published online: October 7, 2025 Processing time: 64 Days and 15.4 Hours
Abstract
Autoimmune liver disease overlap syndrome (OS) is a rare and clinically significant condition that has received limited attention in microbiome research. In their recent study, Wang et al combined 16S rRNA sequencing with untargeted metabolomics to characterize the gut-liver axis in OS, identifying shared features of dysbiosis in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), and unique signatures, including enrichment of Klebsiella and Escherichia and depletion of aromatic amino acids. In this letter, we critically appraise these findings, emphasizing that OS should be considered a distinct immunometabolic phenotype rather than a simple mixture of AIH and PBC. We discuss the potential mechanistic relevance of the Fusicatenibacter-tyrosine relationship, highlight the clinical implications of integrating microbiota-metabolite analyses, and outline the limitations that future studies must address.
Core Tip: Autoimmune liver disease overlap syndrome, involving features of both primary biliary cholangitis and autoimmune hepatitis, poses diagnostic and therapeutic challenges due to its complex pathophysiology. This letter highlights recent evidence linking gut microbiota alterations and serum metabolite changes to liver function in affected patients. The integration of microbial and metabolic data revealed novel interaction networks that may serve as biomarkers for disease differentiation and progression.
