Integrated Analysis of Gut Microbiota and Fecal Metabolites in Chinese Patients With Rheumatoid Arthritis: Associations With Disease Activity.

Abstract

Aim: Rheumatoid arthritis (RA) is a chronic autoimmune disease with intestinal dysbiosis implicated through the gut-joint axis. This study aimed to delineate fecal microbiome and metabolomic signatures in RA and identify biomarkers associated with disease activity.

Method: Twenty-eight RA patients and 19 healthy controls were included in this cross-sectional study. Gut microbiota was characterized by 16S rRNA sequencing with operational taxonomic unit (OTU) and amplicon sequence variant (ASV) analysis. Fecal metabolites were profiled using untargeted metabolomics. Correlations between microbiota, metabolites, and disease activity indices were assessed.

Results: RA patients showed altered alpha diversity and distinct microbial composition versus healthy controls. Eight differential genera and three species were identified based on the combined OTU and ASV analyses. Allisonella was enriched in RA and positively correlated with disease activity, whereas Bifidobacterium adolescentis showed a negative correlation trend with autoantibody/inflammatory markers. Metabolomic analysis revealed 31 and 36 altered metabolites in both ion modes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated dysregulation of unsaturated fatty acid biosynthesis and tryptophan metabolism. Microbiota-metabolite pairs correlated with disease activity.

Conclusion: RA is characterized by distinct gut microbiota and fecal metabolite alterations associated with disease activity. Specific microbial taxa and metabolic pathways may serve as biomarkers, lending further support to the gut-joint axis in RA pathogenesis.