Oral Health, Inflammation, and the Burden of Multiple Long-Term Conditions: Cross-Sectional Analyses from UK Biobank and NHANES

Background: The contribution of oral inflammatory conditions to systemic disease burden remains underexplored within multimorbidity frameworks. Emerging evidence suggests that periodontal inflammation may play a role in the clustering of chronic diseases, yet few studies have evaluated this at a population level using robust datasets. The aims of this study were to investigate whether periodontal diseases are associated with Multiple long-term conditions (MLTCs) burden and severity in two population-based cohorts and to examine whether systemic inflammatory biomarkers mediate these associations. Materials and Methods: We analyzed two population-based cohorts: the UK Biobank (UKB; n = 500,612) and the US National Health and Nutrition Examination Survey (NHANES; n = 10,714). MLTCs were defined as the coexistence of ≥2 chronic diseases. Associations between periodontal diseases and MLTCs were assessed using multivariable logistic and multinomial logistic regression. Causal mediation analyses examined the contribution of systemic inflammatory markers. Results: Approximately half of all participants had MLTCs. The prevalence of periodontal diseases was 17.8% in UKB (self-reported symptoms), and 42.3% in NHANES (clinically assessed). Periodontal diseases were independently associated with greater odds of MLTCs in both UKB (OR 1.12; 95% CI 1.10–1.14) and NHANES (OR 1.22; 95% CI 1.09–1.37). Associations were stronger among adults aged ≤ 60 years. A consistent dose-response relationship was observed between periodontal status and the number and severity of chronic conditions, as well as inflammatory-related MLTCs. Mediation analyses suggested partial effects through white blood cell count, neutrophils, and C-reactive protein. Conclusions: Periodontal inflammation is independently associated with greater multimorbidity burden, particularly in younger adults. Systemic inflammation may offer a plausible biological link, and these findings position oral health as an underrecognized and modifiable target in multimorbidity prevention and management frameworks, warranting prospective investigation.