Deciphering the Genetic Association Between the <scp>FODMAP</scp> Diet and Recurring Oral Aphthae—The Mediating Role of Ferroptosis

The incidence of recurrent oral aphthae (ROA) is on the rise. Its etiology is unknown, particularly its relationship with the FODMAP diet. This investigation delved into their genetic correlation and elucidated the role of ferroptosis. Two-sample Mendelian randomization (MR) analysis was performed, and mediation MR analysis to investigate the relationship between the FODMAP Diet, Ferroptosis, and ROA using GWAS data from Finngen for ROA, deCODE for ferroptosis, and UKB for the FODMAP Diet. Subsequently, a two-step mediation analysis was conducted to examine the mediating role of Ferroptosis in the association between the FODMAP Diet and ROA. MR revealed a protective association between dried fruit and tea consumption and the risk of ROA, while poultry and beef intake showed a significant positive correlation with ROA risk. Subsequent investigation into iron-related genes identified 10 key proteins that may mediate the impact of dietary habits on ROA development. Mediation analysis demonstrated that tea consumption indirectly influenced ROA progression by modulating Dihydrolipoamide Dehydrogenase (DLD) protein expression, accounting for 21.15% of the total effect. Sensitivity analyses confirmed our results, enhancing the statistical validity of our findingsstatistical validity. This study underscores the significance of the FODMAP Diet in preventing and treating ROA. It proposes the clinical utility of DLD as a diagnostic and therapeutic target for ROA and underscores the critical role of dietary management.