Multi-omics integration reveals oral microbiota-metabolite-immune interactions in recurrent aphthous ulceration

Recurrent aphthous ulceration (RAU) is a chronic inflammatory disease of the oral mucosa, but its underlying mechanisms remain unclear. In this study, integrated oral microbiome, serum metabolomics, and immune analyses were performed in 16 RAU patients and 16 healthy controls. 16S rRNA sequencing revealed suggestive compositional shifts in the oral microbiota of RAU patients, with nominal trends toward enrichment of Fusobacterium , Moraxella , and Granulicatella and depletion of Treponema and Lancefieldella . PICRUSt2 analysis indicated functional shifts associated with amino acid metabolism and inflammatory signaling. Untargeted metabolomics identified extensive metabolic remodeling, including altered gamma-glutamylcysteine, eicosapentaenoic acid (EPA), crocetin, pristanic acid, and cysteinyl-containing dipeptides, suggesting disturbances in oxidative stress regulation and inflammatory lipid metabolism. KEGG analysis further demonstrated enrichment of pathways related to cysteine and methionine metabolism, purine metabolism, taurine and hypotaurine metabolism, and primary bile acid biosynthesis. Immune profiling showed significant alterations in CD4 + T lymphocyte subsets, accompanied by elevated IL-1, IL-6, and TNF-α levels. Integrated correlation analysis revealed strong associations among differential microbial taxa, metabolites, and inflammatory cytokines. Collectively, these findings suggest that coordinated alterations in the oral microbiota, serum metabolites, and immune responses are associated with RAU, providing new insights into the biological features of RAU and potential therapeutic targets for further investigation.