Periodontal diseases are associated with dysbiotic oral microbial communities, but clinically applicable measures that reflect microbial burden across disease severity and progression remain limited. This study aimed to assess the oral microbial burden of periodontal diseases by evaluating salivary and subgingival lipopolysaccharide (LPS) activity and lipoteichoic acid (LTA) levels, to explore their relationships with microbial dysbiosis and clinical periodontal parameters in individuals with periodontal health (n = 52), gingivitis (n = 194), and periodontitis of varying stages, grades, and furcation involvement (n = 78), and to assess their diagnostic potential.

Saliva and subgingival plaque samples from 324 SECRETO cohort participants were analyzed for microbial virulence factors using a recombinant Factor C assay for LPS and enzyme-linked immunosorbent assay (ELISA) for LTA. Microbial dysbiosis was assessed using a sequencing-derived, simplified dysbiosis index, calculated from subgingival 16S rRNA gene sequencing and salivary shotgun metagenomic profiles, based on the relative abundances of health-associated and periodontitis-associated taxa.

Subgingival LPS activity was significantly higher in periodontitis patients compared to healthy individuals and increased progressively across disease stages and grades. Salivary LPS activity differed only by periodontal diagnosis and correlated with full-mouth bleeding score (FMBS). LTA levels showed no statistical variations across periodontal conditions. Subgingival LPS activity and LPS/LTA ratio were strongly associated with simplified dysbiosis index. Salivary dysbiosis index was significantly higher in patients with furcation involvement. Receiver operating characteristic (ROC) analyses identified subgingival LPS, salivary LPS, and simplified dysbiosis index as diagnostic biomarkers with good clinical utility (area under the curve [AUC] 0.59–0.87).

This study highlights the importance of periodontitis diagnoses, stages and grades of periodontitis and furcation involvement as determining factors for increased salivary and subgingival bioburden. In addition, LPS activity could be used as a reliable periodontal biomarker, while the LPS/LTA ratio is an indirect indicator of microbial dysbiosis.