Parvimonas micra is a specifically enriched bacterium in advanced canine periodontal disease and its effects are...

Canine periodontitis is a prevalent chronic inflammatory disease, with its pathological progression closely associated with oral microbiome dysbiosis and dysregulated host immune responses. This study aimed to characterize oral microbiome changes across different stages of canine periodontitis, identify bacteria associated with advanced disease and evaluate the immunomodulatory potential of adipose-derived stem cell exosomes (ADSCs-exosomes). We analyzed pooled subgingival and supragingival plaque samples collected from multiple oral sites in 60 dogs with clinical stages S0-S4 using 16S rRNA sequencing, and performed in vitro cell assays, ADSCs-exosomes isolation and characterization. Alpha-diversity analysis showed that, in this cohort and under our pooled oral sampling design, advanced periodontitis was associated with increased community richness and altered evenness at the subject level, while beta-diversity analysis confirmed marked structural differences among study groups (R² = 0.161, P = 0.001). P. micra showed significantly higher abundance in severe periodontitis (S4) and was identified by linear discriminant analysis effect-size (LEfSe), random forest, and analysis of variance (ANOVA) analyses (linear discriminant analysis (LDA) > 3.5, P < 0.01), suggesting an association with advanced disease. In vitro, P. micra reduced canine macrophage cell (DH82) (P < 0.05) viability and promoted a pro-inflammatory phenotypes. ADSCs-exosomes were internalized by canine macrophages and significantly downregulated pro-inflammatory cytokines (IL-1β, IL-6, iNOS) and upregulated anti-inflammatory markers (Arg-1, CD163, and IL-10) (P < 0.05), thereby partially reversing the inflammatory imbalance induced by P. micra. Together, these findings identify P. micra as a candidate bacterium associated with advanced canine periodontitis and suggest that ADSCs-exosomes may have potential as a host-modulatory therapeutic strategy in this disease.