Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Multi-omics analysis reveals gut microbiota-metabolite interactions and their association with liver function in autoimmune overlap syndrome
Qi Wang, Li-Na Sun, Han Shi, Xin-Yue Ma, Wen Gao, Bin Xu, Xiao Lin, Yan-Min Liu, Chun-Yang Huang, Rong-Hua Jin
Qi Wang, Li-Na Sun, Han Shi, Rong-Hua Jin, Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Qi Wang, Li-Na Sun, Han Shi, Rong-Hua Jin, Beijing Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Qi Wang, Li-Na Sun, Han Shi, Rong-Hua Jin, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Qi Wang, Li-Na Sun, Han Shi, Xin-Yue Ma, Wen Gao, Bin Xu, Xiao Lin, Yan-Min Liu, Chun-Yang Huang, Second Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
Qi Wang, Center of Liver Diseases Division, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Rong-Hua Jin, Changping Laboratory, Capital Medical University, Beijing 102206, China
Co-first authors: Qi Wang and Li-Na Sun.
Co-corresponding authors: Chun-Yang Huang and Rong-Hua Jin.
Author contributions: Wang Q, Sun LN, Shi H, and Ma XY collected the data; Wang Q and Lin X performed the data analysis; Wang Q, Sun LN prepared the manuscript; Gao W, Xu B, and Liu YM revised the manuscript; Jin RH and Huang CY developed the methodology; Jin RH supervised the research; Huang CY conceptualized the study; All authors have read and agreed to the published version of the manuscript.
Supported by WBE Liver Foundation, No. WBE2022018; 2022 Young and Middle-aged Talents Incubation Project (Youth Innovation) of Beijing Youan Hospital, Capital Medical University, No. BJYAYY-YN-2022-09; and 2023 Young and Middle-aged Talents Incubation Project (Youth Innovation) of Beijing Youan Hospital, Capital Medical University, No. BJYAYYYN2023-14.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Beijing Youan Hospital, Capital Medical University (Approval No. LL-2024-026-K).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at
ronghuajin@ccmu.edu.cn.
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: Rong-Hua Jin, MD, Doctor, Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing 100015, China.
ronghuajin@ccmu.edu.cn
Received: February 25, 2025
Revised: April 26, 2025
Accepted: June 16, 2025
Published online: July 7, 2025
Processing time: 130 Days and 17.5 Hours
BACKGROUND
Autoimmune liver diseases, including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and their overlap syndrome (OS), involve immune-mediated liver injury, with OS occurring in 1.2%-25% of PBC patients. OS carries a higher risk of cirrhosis, hepatocellular carcinoma, and reduced survival. While its pathogenesis remains unclear, gut microbiota dysbiosis and serum metabolite alterations may play key roles. This study uses 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) metabolomics to compare gut microbiota and serum metabolites among PBC, AIH, and OS patients, and explores their associations with liver function.
AIM
To differentiate OS from PBC and AIH based on gut microbiota, serum metabolites, and liver function.
METHODS
Gut microbiota profiles were analyzed using 16S rRNA sequencing, while untargeted serum metabolomics was conducted via LC-MS. Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC, AIH, and OS groups. Correlation analyses and network visualization techniques were applied to elucidate the interactions among liver function parameters, gut microbiota, and serum metabolites in OS patients.
RESULTS
Compared to patients with PBC or AIH, OS patients demonstrated significantly reduced microbial diversity and richness. Notable taxonomic shifts included decreased abundances of Firmicutes, Bacteroidetes, and Actinobacteria, alongside increased levels of Proteobacteria and Verrucomicrobia. Distinct serum metabolites, such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide, were identified in OS patients. Correlation analysis revealed that aspartate aminotransferase (AST) levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine. A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.
CONCLUSION
OS patients show decreased gut microbiota diversity and unique serum metabolites. Multi-omics linked AST, Fusicatenibacter, and L-Tyrosine, revealing OS mechanisms and diagnostic potential.
Core Tip: This study characterizes the distinct gut microbiome and serum metabolite profiles in overlap syndrome (OS), a severe condition combining features of primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). These findings provide the first comprehensive evidence linking gut microbiota dysbiosis with specific metabolic alterations in OS, offering new insights into disease mechanisms and potential diagnostic biomarkers for distinguishing OS from PBC or AIH alone. The microbial-metabolite network discovered in this study may open new avenues for therapeutic interventions targeting the gut-liver axis in autoimmune liver diseases.
