Integrative Multi‐Omics Analysis Identifies FTO as a Genetic and Epigenetic Link Between Metabolic Susceptibility and Staphylococcus aureus ‐Induced Airway Remodeling in Chronic Rhinosinusitis

ABSTRACT This study identifies fat mass and obesity‐associated protein (FTO) as a pivotal link between metabolic predisposition and pathogenesis associated with Staphylococcus aureus in chronic rhinosinusitis (CRS). These findings were established through the application of an integrative multi‐omics framework. We demonstrate that S. aureus upregulates FTO, which functions as an m 6 A demethylase to stabilize the Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1). This molecular axis suppresses GSK‐3β and promotes β‐catenin nuclear translocation, thereby driving epithelial‐mesenchymal transition (EMT) and pathological mucosal remodeling. By mapping the FTO‐MALAT1‐GSK‐3β/β‐catenin signaling network, this research elucidates how metabolic susceptibility facilitates infection‐triggered epithelial reprogramming. These findings establish FTO as a promising biomarker and potential therapeutic target, providing a systemic foundation for personalized CRS treatment strategies.