Association between gut microbial alterations and mucosal- associated invariant T (MAIT) cell dysregulation in rheumatoid arthritis

Background Mucosal-associated invariant T (MAIT) cells are activated by microbe-derived metabolites and enriched at mucosal barriers, linking their biology closely to the gut microbiota. In rheumatoid arthritis (RA), MAIT-microbiota interactions may represent an underexplored pathogenic axis. Methods Peripheral blood MAIT cells were analysed by flow cytometry in 36 RA patients and 31 healthy controls (HCs). Fecal samples underwent 16S rRNA gene sequencing to characterize gut microbiota composition and PICRUSt2-based functional prediction analysis was performed to explore microbial metabolic pathways. Associations between microbial taxa, MAIT cells and clinical parameters were evaluated by non-parametric statistics and Spearman analysis. Results Circulating MAIT cells were significantly reduced in RA, particularly the loss of CD8⁺MAIT cells ( P  < 0.01), and were further decreased in patients with moderate and high disease activity (M-HDA) ( P  > 0.05). Compared to HCs, RA patients exhibited reduced gut microbial richness and diversity. Moreover, reduced genera Subdoligranulum , Parasutterella and Alloprevotella correlated positively with total and CD8⁺MAIT cells, whereas increased genus Eggerthella correlated negatively ( P  < 0.05). Functional prediction revealed enriched genes ( ssuE , ribA/RIB1 , ribF , nudJ , RIB7 ) of riboflavin biosynthesis pathways in RA, with RIB7 expression significantly correlated with MAIT cell frequency ( P  = 0.004). Conclusion RA is characterized by concurrent MAIT-cell depletion and gut microbiota dysbiosis, with specific microbial taxa linked to MAIT-cell alterations. The enrichment of riboflavin-pathway genes suggests a potential mechanism connecting microbial metabolism to MAIT-cell dysregulation. These findings support a microbiota–MAIT axis in RA pathogenesis and highlight potential targets for therapeutic intervention.