From oral infection to pulmonary inflammation: periodontal pathogens and their potential role in COPD susceptibility.

BACKGROUND: Oral health significantly impacts overall health. Periodontal disease and chronic obstructive pulmonary disease (COPD) are prevalent chronic inflammatory conditions among older adults, but their causal link is not well-established. METHODS: Multivariable logistic regression, including subgroup, sex-stratified, and interaction analyses, was used to investigate the link between self-reported periodontal disease and COPD. Two-sample Mendelian randomization (MR) was utilized to explore causality, primarily through inverse-variance weighting (IVW), and supported by four additional MR approaches. Sensitivity analyses were performed to evaluate pleiotropy and heterogeneity. Normal human bronchial epithelial cells were stimulated in vitro with the periodontal pathogens F. nucleatum and P. gingivalis. The expression levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were then quantified using qPCR and chemiluminescence immunoassay. In vivo, a combined rat model of periodontitis and COPD was established to compare pulmonary inflammatory severity with a COPD-only model. RESULTS: Multivariable logistic regression revealed significant associations between self-reported periodontal disease, oral hygiene practices, and COPD. The self-reported periodontal disease-COPD association was moderated by hypertension and flossing behavior. Mendelian randomization studies provided suggestive, exploratory evidence that periodontal disease may be associated with a higher risk of COPD in European populations, although the association did not survive multiple-testing correction and was not observed in East Asian populations. In vitro, both pathogens significantly upregulated IL-6 and IL-8 at both mRNA and protein levels. In vivo, rats with comorbid periodontitis and COPD exhibited significantly exacerbated pulmonary inflammation compared with those having COPD alone. CONCLUSION: Periodontal disease may promote COPD pathogenesis, with in vitro data supporting a direct pro-inflammatory role of P. gingivalis and F. nucleatum in airway epithelium. In vivo, periodontitis as a complex disease state exacerbates pulmonary inflammation in COPD. Maintaining good oral hygiene may represent a potential supportive strategy that warrants further investigation in interventional studies, with potential public health implications, especially among high-risk populations.