Erythrocyte Membrane Fatty Acids and Periodontitis Risk: A Population, Network Pharmacology and Molecular Docking Study.

INTRODUCTION AND AIMS: Erythrocyte membrane fatty acid composition serves as a reliable biomarker reflecting dietary lipid intake and metabolic status. To investigate associations between erythrocyte membrane fatty acid profiles and periodontitis risk, and explore the underlying mechanisms through integrated network pharmacology and molecular docking approaches.

METHODS

A hospital-based case-control study enrolled 108 newly diagnosed periodontitis patients and 144 controls without periodontitis. Thirty-eight erythrocyte membrane fatty acids were quantified using gas chromatography-mass spectrometry. Least absolute shrinkage and selection operator regression identified key fatty acids for constructing a composite fatty acid score. Network pharmacology analysis identified overlapping targets between fatty acids and periodontitis, followed by molecular docking validation of fatty acid-target interactions with the core hub gene.

RESULTS

Twenty-four erythrocyte membrane fatty acids were successfully detected. Eight saturated (C14:0-C24:0), four monounsaturated (C16:1, C18:1, C20:1, C24:1), and six polyunsaturated fatty acids (omega-3: C20:5, C22:5, C22:6; omega-6: C20:2, C20:3, C20:4) showed positive associations with periodontitis risk (adjusted odds ratios 1.31-1.66). A composite fatty acid score constructed from 15 least absolute shrinkage and selection operator-selected fatty acids strongly associated with periodontitis risk (odds ratio = 2.77, 95% confidence interval: 1.93-3.98), with dose-response relationship confirmed by restricted cubic spline analysis. Network pharmacology analysis identified 119 overlapping targets, with interleukin-6 (IL-6) as the top hub gene. Molecular docking revealed strong binding affinity between all 15 selected fatty acids and IL-6.

CONCLUSION

Erythrocyte membrane fatty acid profiles are significantly associated with periodontitis risk. This association is potentially mediated through IL-6 inflammatory pathways, which provides mechanistic insights into fatty acid-mediated periodontal inflammation and offers novel targets for nutritional intervention strategies.