Oral Microbial Dysbiosis and Pathogenic Functional Shifts in Mucosa‐Dominant Pemphigus Vulgaris and Low‐Risk Mucous Membrane Pemphigoid

BACKGROUND: Mucosal-dominant pemphigus vulgaris (MD-PV) and low-risk mucous membrane pemphigoid (LR-MMP) are autoimmune bullous diseases primarily affecting the oral mucosa, yet their oral microbiome profiles remain inadequately characterized. METHODS: Using 16S rRNA sequencing of saliva from 21 MD-PV patients, 26 LR-MMP patients, and 14 healthy controls (HC), we analyzed microbial diversity, differential taxa (LEfSe), and functional potential (PICRUSt2/BugBase). RESULTS: Both patient groups showed significant microbial restructuring without major richness changes, featuring increased Firmicutes and decreased Proteobacteria. Disease-specific signatures included Flavobacteriia enrichment in MD-PV and Coriobacteriia/Actinobacteria in LR-MMP. Shared metabolic alterations involved "Biosynthesis of amino acids," "Phosphotransferase system," and "Ribosome" pathways, while distinct activations included "all-trans-farnesol biosynthesis" in MD-PV and "peptidoglycan biosynthesis" in LR-MMP. Phenotype prediction revealed increased Gram-positive bacteria and reduced pathogenic and stress-tolerant taxa. Microbial dysbiosis scores positively correlated with clinical disease severity. CONCLUSION: Our study identifies distinct oral microbial dysbiosis patterns in MD-PV and LR-MMP, with conserved functional shifts and disease-specific metabolic adaptations. The microbiota-severity correlation highlights its potential role in disease mechanisms, offering new insights for therapeutic exploration. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR2500105460.