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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                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a052), gingivitis (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0194), and periodontitis of varying stages, grades, and furcation involvement (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a078), and to assess their diagnostic potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2010linked immunosorbent assay (ELISA) for LTA. Microbial dysbiosis was assessed using a sequencing\u2010derived, simplified dysbiosis index, calculated from subgingival 16S rRNA gene sequencing and salivary shotgun metagenomic profiles, based on the relative abundances of health\u2010associated and periodontitis\u2010associated taxa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2010mouth 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\u20130.87).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov Identifier: NCT01934725.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>Periodontitis is a common inflammatory disease that affects the tissues supporting the teeth and can lead to tooth loss and broader health consequences if not properly managed. This study explored whether measures of oral microbial burden, particularly bacterial components such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), could help explain differences in periodontal disease severity and progression. Saliva and subgingival plaque samples were analyzed from individuals with periodontal health, gingivitis, and different stages and grades of periodontitis. We found that microbial burden, especially subgingival LPS activity, increased consistently with more severe and rapidly progressing forms of periodontitis and was closely associated with clinical signs of inflammation. In contrast, LTA levels showed limited variation across disease categories. Importantly, LPS\u2010related measures demonstrated good ability to distinguish periodontal health from disease. These findings suggest that assessing microbial burden, particularly LPS activity, may provide clinically useful information beyond traditional periodontal assessments and could support improved disease classification, risk assessment, and the development of more personalized periodontal care strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70140","type":"journal-article","created":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T13:03:25Z","timestamp":1779023005000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Microbial burden of periodontal diseases and its clinical application: The stage, grade, and furcation matter"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9196-7128","authenticated-orcid":false,"given":"Anbo","family":"Dong","sequence":"first","affiliation":[{"name":"Centre for Host\u2010Microbiome Interactions, Faculty of Dentistry, Oral and 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