Porphyromonas Gingivalis Sialidase Reshapes Gut Microbiota And Systemic Immunity

Porphyromonas gingivalis can alter the gut microbiota and serum metabolites. However, its sialidase in modulating gut microbiota composition, host metabolism, and immune responses remains unexplored. This study aims to investigate the effects of Porphyromonas gingivalis sialidase on the gut microbiota and serum metabolites, and analyze the correlation between changes in gut microbiota and metabolites induced by Porphyromonas gingivalis sialidase and systemic immune responses. C57BL/6 mice were oral gavaged Porphyromonas gingivalis W83, Porphyromonas gingivalis W83 silidase mutant strain (∆PG0352), or an equal volume of PBS twice a week for five consecutive weeks. Spleens were subjected to hematoxylin and eosin staining and enzyme linked immunosorbent assay to assess spleen inflammatory levels. Gut microbiota profiles were characterized using 16S rRNA sequencing, and serum metabolites were analyzed via untargeted metabolomics. Multivariate statistical analyses integrated microbial, metabolic, and immunological datasets to identify interaction networks. Porphyromonas gingivalis W83 group exhibited more severe spleen inflammation and higher levels of inflammatory cytokines compared to other two groups. The 16S rDNA analysis revealed significant differences in 19 bacterial genera between the Porphyromonas gingivalis W83 group and the ∆PG0352 group, and metabolomics identified distinct alterations in metabolite profiles among groups, with twelve key differential metabolites identified. Correlations demonstrated phosphatidylcholine emerged as a central metabolite, exhibiting strong positive correlations with Staphylococcus, Prevotellaceae_UCG-001, and IL-1β, confirming its role as a hub linking metabolic shifts to immune activation. Porphyromonas gingivalis sialidase exacerbated systemic inflammation by reshaping gut microbial ecology, driving phosphatidylcholine-centered metabolic reprogramming, and amplifying splenic immune responses.