Abstract MP44: Nitrite Generating Capacity Assessed Through the Oral Microbial Metagenome is Associated With Cardiometabolic Risk

Abstract

Introduction: Nitric oxide (NO) is important for cardiometabolic health. The enterosalivary nitrate-nitrite-NO pathway generates NO following oral microbiota-mediated production of salivary nitrite. We investigated the association between the abundance of genes in this pathway and cardiometabolic biomarkers. Hypothesis: Microbial genes favoring increased oral nitrite generation are associated with better cardiometabolic profile. Methods: We enrolled 784 diabetes-free adults in the Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS). Subgingival plaques were collected from 6-8 teeth/participant. 16S rRNA microbial genes (Illumina, MiSeq) were sequenced; PICRUSt2 estimated abundance of microbial genes in the nitrate-nitrite pathway associated with either nitrite generation or depletion. Gene abundance was summed within each group, and a ratio between nitrite generation to depletion (GDR) was calculated; higher levels suggest increased nitrite generating capacity. Systolic and diastolic blood pressure were measured and HbA1C, insulin, and glucose levels were determined in fasting blood. Z-scores were calculated for cardiometabolic biomarkers and averaged to form a cardiometabolic z-score (CMZ-score). Adjusted multivariable linear models were used to regress the CMZ-score and individual Z-scores on GDR. Results: Participants were 69% female and aged 19-58 years (mean=32±9). Mean CMZ-score was 0.00±0.7. Mean (range) GDR was 1.88 (0.22-7.84). Mean CMZ-scores (SE) across GDR quartiles were 0.17 (0.06), 0.01 (0.05), -0.04 (0.05), and -0.14 (0.05), p-value for trend=0.02. Linear regression coefficients summarizing associations between GDR and individual Z-scores (Table) show lower Z-score for systolic and diastolic blood pressure, HbA1C, and insulin levels in those with higher GDR. Conclusions: Increased capacity for nitrite production by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.