Exposome-wide association study of environmental toxicants and periodontitis among United States adults

To systematically evaluate associations between environmental toxicants and periodontitis and to quantify the mediating role of systemic inflammatory biomarkers.

We extracted data from National Health and Nutrition Examination Survey (NHANES) 2013-2014. The study covers 73 environmental toxicants spanning 12 categories. Exposome-wide association study (ExWAS) was used to identify individual toxicant associations, and adaptive elastic net regularization was employed to develop an environmental risk score (ERS). Mediation analysis quantified the contribution of inflammatory biomarkers to observed associations RESULTS: Among 1210 participants, 49.4 % were male and 50.6 % were female. The ExWAS identified 29 toxicants across 9 categories significantly associated with periodontitis. Notably, detectable monohydroxybutenyl mercapturic acid (MHBMA2) levels were associated with a 2.798-fold higher periodontitis odds (95 % CI: 1.799-4.352) versus undetectable levels. Stratified analyses revealed that associations were stronger among males and younger adults (< 60 years). The ERS, derived from 17 prioritized toxicants via elastic net regression, demonstrated a significant positive dose-response relationship with periodontitis risk, where each IQR increase was associated with a 59.7 % higher disease risk (OR = 1.597). Mediation analysis indicated that white blood cell count (11.5 %), neutrophils (10.2 %), monocytes (5.1 %), systemic immune-inflammation index (6.3 %), neutrophil-to-lymphocyte ratio (5.7 %), and systemic inflammation response index (7.4 %) significantly mediated toxicant-periodontitis associations.

This nationally representative exposome-wide investigation identified significant associations between multiple environmental toxicants and periodontitis, with inflammatory pathways partially mediating these relationships. These findings establish potential environmental etiological factors for periodontitis and highlight specific toxicants as targets for exposure reduction strategies to improve periodontal health at the population level.