Glycolysis Plays a Critical and Dual Role in Periodontitis

ABSTRACT Glycolysis is a fundamental metabolic pathway that breaks down glucose into pyruvate and lactate, critically shaping immune responses and cell functions in various diseases. Periodontitis is a chronic inflammatory disease marked by progressive destruction of periodontal tissues. Recent evidence has revealed that glycolysis plays a critical and dual role in periodontitis. On one hand, metabolic reprogramming toward glycolysis amplifies inflammatory cascades in various periodontal cells, driving periodontitis progression through multiple mechanisms. On the other hand, the end‐product of glycolysis, lactate, and its lactylation exert anti‐inflammatory effects in periodontitis by modulating immune responses and regulating bone remodeling. Moreover, emerging therapeutic strategies targeting glycolytic flux aim to inhibit periodontal inflammation progression and promote periodontal tissue regeneration. In this review, we illustrate the dual mechanisms of glycolysis in periodontitis pathogenesis and highlight its potential as a therapeutic target for metabolic intervention.