Multi-omics analysis reveals gut microbiota-metabolite interactions and their association with liver function in autoimmune overlap syndrome

Jul 14, 2025World journal of gastroenterology

Gut bacteria and their chemical products linked to liver function in autoimmune overlap syndrome

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Abstract

Patients with overlap syndrome (OS) exhibit significantly reduced microbial diversity and richness compared to those with primary biliary cholangitis (PBC) or autoimmune hepatitis (AIH).

OS is characterized by notable taxonomic shifts in gut microbiota, including decreased abundances of specific bacterial groups.
Distinct serum metabolites, such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide, are identified in OS patients.
Aspartate aminotransferase (AST) levels are negatively associated with certain gut bacteria and the metabolite L-Tyrosine in OS patients.
A microbial-metabolite network indicates a strong association between specific gut bacteria and L-Tyrosine in the context of OS.
Findings suggest potential mechanisms and diagnostic markers for OS through the analysis of gut microbiota and serum metabolites.

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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 conductedLC-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. via

RESULTS: Compared to patients with PBC or AIH, OS patients demonstrated significantly reduced microbial diversity and richness. Notable taxonomic shifts included decreased abundances of,, and, alongside increased levels ofand. 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 genusand the metabolite L-Tyrosine. A microbial-metabolite network diagram further confirmed a strong association betweenand L-Tyrosine in OS patients. Firmicutes Bacteroidetes Actinobacteria Proteobacteria Verrucomicrobia Fusicatenibacter Fusicatenibacter

CONCLUSION: OS patients show decreased gut microbiota diversity and unique serum metabolites. Multi-omics linked AST,, and L-Tyrosine, revealing OS mechanisms and diagnostic potential. Fusicatenibacter

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Multi-omics analysis reveals gut microbiota-metabolite interactions and their association with liver function in autoimmune overlap syndrome

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