Systemic Lipidomics Identifies Altered Ceramide–Phospholipid Balance Associated With Periodontitis Severity: A Cross‐Sectional Study With 12‐Year Follow‐Up

AIM: To investigate whether periodontitis stage and grade are associated with circulating active lipid mediators and whether baseline lipid species predict periodontitis progression. MATERIALS AND METHODS: The study included 473 Finnish participants from the Parogene cohort undergoing coronary angiography, with 12-year follow-up data available for 117 individuals. Periodontal status was assessed clinically and radiographically. Plasma ceramides (Cer) and phosphocholines (PC) were quantified by LC-MS/MS, and cardiovascular risk scores (CERT1 and CERT2) were calculated. RESULTS: Several Cer:Cer and Cer:PC ratios increased with periodontitis stage, grade and edentulousness, whereas most PC species decreased. Cer(d18:1/16:0)/PC(16:0/22:5), Cer(d18:1/18:0)/Cer(d18:1/24:0), Cer(d18:1/18:0)/PC(16:0/22:5) and Cer(d18:1/24:1)/PC(16:0/22:5) were associated with all periodontal measures. CERT2 was independently associated with both stage and grade. In cross-sectional analyses, periodontitis was associated with multiple lipid species both directly and indirectly through systemic inflammation. In longitudinal analyses, baseline lipid levels did not predict periodontitis progression. CONCLUSION: Periodontitis severity was found to be associated with systemic ceramide and phospholipid profiles, particularly Cer:PC ratios, whereas baseline lipid levels were not associated with subsequent disease progression. These findings suggest that systemic inflammation substantially mediates the relationship between periodontitis and circulating lipid species, linking periodontitis with broader disturbances in lipidomic homeostasis.