Periodontitis and Endotoxemia: Clinical and Microbiological Insights

Aim Endotoxemia has been proposed as a link between periodontitis and systemic complications through the translocation of lipopolysaccharide (LPS) from inflamed periodontal sites into the bloodstream. This study aimed to investigate subgingival and serum LPS activities and their correlations with periodontal clinical and microbiological parameters. Materials and Methods Two‐hundred and seventy participants with gingivitis and periodontitis from the SECRETO Oral cohort were included in the study. Serum and subgingival plaque samples were analysed for LPS activity using the recombinant Factor C assay, and subgingival microbiota were profiled by 16S rRNA sequencing. Dysbiosis indices and taxonomic associations were assessed through multivariate regressions and MaAsLin2 models adjusted for clinical and demographic covariates. Functional pathways were inferred using PICRUSt2. Results Serum LPS activities were significantly elevated in periodontitis patients compared to gingivitis patients and correlated with the subgingival microbial dysbiosis index (SMDI). Subgingival LPS was also significantly higher in periodontitis patients and showed strong associations with subgingival bacterial load and SMDI. Subgingival LPS explained 10% of serum LPS variations. Differential abundance analysis identified Fretibacterium as positively associated with both subgingival and serum LPS activities. Functional prediction revealed enrichment of bacterial motility and invasion pathways, with depletion of host defence functions, supporting a mechanistic link between subgingival dysbiosis, LPS translocation and systemic endotoxemia. Conclusion These findings provide novel evidence that elevated serum LPS activities are closely linked with periodontitis diagnosis, associated with subgingival dysbiosis, and highlight the periodontal niche as a source of systemic endotoxemia. In addition, it identified Fretibacterium as the main contributor to both subgingival and serum LPS activities.