Oral microbial nitrate metabolism is associated with lower prevalence of prediabetes

The oral microbiome is a key microbial interface for dietary or oral nitrate metabolism, yet its role in early glycemic dysregulation remains poorly defined. In a population-based cohort (n = 472), we perform metagenomic profiling of tongue dorsum microbiomes and identify 11 taxa and nine microbial pathways associated with prediabetes. Among these, Rothia mucilaginosa and microbial nitrate reduction emerge as the only taxon and the strongest pathway associated with lower prediabetes prevalence. Individuals without prediabetes show higher salivary nitrate and nitrite concentrations, supporting enhanced oral nitrate bioavailability. Functional characterization of an isolated Rothia mucilaginosa strain demonstrates its capacity to mediate both nitrate-nitrite-NO and nitrate-nitrite-NH₄⁺ pathways under oxygen-limited conditions. Incorporating nitrate metabolism-associated microbial features into clinical risk factors improves risk stratification for progression to prediabetes. These findings support oral nitrate metabolism as a microbial pathway linking oral ecology to systemic metabolic health and suggest that tongue cleaning may modulate microbial functions involved in this pathway.