Beyond Acidification: Microbial Lactate in the Oral Microbiome-Host Axis

Lactate, the major acidic end-product of carbohydrate metabolism in the oral microbiome, has long been recognized as a key driver of tooth demineralization by lowering the tooth surface pH below the critical threshold for enamel dissolution. Within the framework of the ecological plaque hypothesis, this frequent and prolonged acidification contributes to dysbiosis by favoring acidogenic and aciduric microorganisms. However, accumulating evidence indicates that microbiome-derived lactate plays broader roles in both microbial ecology and host physiology. This review synthesizes current knowledge on the multifaceted functions of lactate within the oral microbiome-host axis. Lactate produced by saccharolytic bacteria, mainly including Streptococcus, Actinomyces, and Lactobacillus, as well as Rothia and Gemella, is extensively used by commensal taxa, including Veillonella, Neisseria, Rothia, and Streptococcus oligofermentans, and is primarily converted into acetate, propionate, and carbon dioxide. These cross-feeding interactions form integral metabolic networks within oral biofilms that are tightly coupled to the production of bioactive molecules, including nitrite, hydrogen peroxide, and hydrogen sulfide, contributing to microbial ecological homeostasis. Nitrite may further enter the systemic circulation and exert physiological effects, such as peripheral vasodilation via nitric oxide production through the nitrate-nitrite-nitric oxide pathway. Furthermore, in addition to directly damaging host cells at high concentrations, lactate may function as a signaling molecule through hydroxycarboxylic acid receptor 1 on host cells, potentially modulating cellular responses by regulating metabolic and signal transduction pathways. Lactate is also transported into cells via monocarboxylate transporters, where it serves as a metabolic substrate for redox regulation and induces epigenetic modifications through histone and non-histone protein lactylation, thereby affecting host cell functions. These multifaceted functions highlight lactate as a metabolic and signaling hub in the oral microbiome-host axis. The modulation of the lactate flux, rather than simply inhibiting microbial lactate production, may offer a new strategy for maintaining and promoting oral and systemic health.