This study highlights the significant effect of the periodontal pathogen Pg on the TMA-TMAO pathway, primarily through modulation of FMO3 expression and regulation of hepatic lipid metabolism, compared to Fn and Sm. Pg uniquely enhances TMAO production, which is closely associated with the progression of systemic diseases, highlighting its potential as a key target in understanding and managing TMAO-related metabolic diseases. Here, FN1 is linked to Other metabolic disease.