<i>Porphyromonas gingivalis</i> sialidase reshapes gut microbiota to affect serum metabolism and splenic immunity: insights from a murine study

Background Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen can alter the gut microbial composition, serum metabolites and systemic immune status in mice. However, the role of its sialidase in modulating these parameters remains unexplored.Objective This study aims to investigate the effects of P. gingivalis sialidase on gut microbiota, serum metabolites and their correlations with systemic immune responses.Design C57BL/6 mice were orally inoculated with P. gingivalis W83, its sialidase-deficient ΔPG0352 mutant or PBS twice weekly following antibiotic pretreatment. After 40 days, spleen samples were collected for histological examination and cytokine analysis. Faecal samples were collected for 16S rRNA sequencing, and the serum samples were analysed by untargeted metabolomics.Results P. gingivalis W83 group exhibited severe splenic inflammation and higher inflammatory cytokine levels than the other two groups. 16S rRNA gene analysis identified 19 differential bacterial genera (including Staphylococcus and Prevotellaceae_UCG-001) between the P. gingivalis W83 and ∆PG0352 groups. Metabolomics detected 12 key differential metabolites mainly involved in energy metabolism and amino acid biosynthesis pathways. Correlation analysis revealed phosphatidylcholine as a central metabolite, positively correlated with Staphylococcus, Prevotellaceae_UCG-001 and IL-1β, confirming its hub role linking metabolic shifts to immune activation.Conclusions P. gingivalis sialidase exacerbated systemic inflammation by reshaping gut microbiota, driving phosphatidylcholine-centred metabolic reprogramming and amplifying splenic immunity.