Metabolic Reprogramming of Macrophages Plays a Dual Role in Periodontitis: From Pathogenesis to Therapy

The pathogenesis of periodontitis is closely intertwined with a complex immune and inflammatory cascade initiated by a dysbiotic dental biofilm. As key regulators of both innate and adaptive immunity, macrophages play a central role in the development and progression of periodontitis. Recent advances in immunometabolism have underscored the significance of metabolic reprogramming in shaping macrophage immune responses and influencing inflammation progression. In this review, we discuss the metabolic reprogramming of macrophages in glucose, lipid, and amino acid metabolism during periodontitis, as well as its intercellular consequences within the periodontal microenvironment. Moreover, we discuss how periodontal inflammatory microenvironmental factors drive this metabolic reprogramming, establishing a bidirectional, self-perpetuating vicious cycle. Finally, we highlight the therapeutic potential of targeting macrophage metabolism and emphasize the dual role of metabolic reprogramming as both a driver of periodontitis progression and a potentially reversible process that can be therapeutically redirected.