Dietary Nitrate Intake and 16S rRNA ‐Inferred Nitrite‐Generating Capacity of the Subgingival Microbiome May Influence Glucose Metabolism: Results From the Oral Infections Glucose Intolerance and Insulin Resistance Study ( ORIGINS )

AIMS: To investigate whether the association between the nitrite-generating capacity of the subgingival microbiome and early cardiometabolic risk biomarkers varies by dietary nitrate intake. MATERIALS AND METHODS: Cross-sectional data from 668 participants (mean age 31 ± 9 years, 73% women) were analysed. Dietary nitrate intake was calculated from food frequency questionnaires. Subgingival 16S rRNA sequencing (Illumina, MiSeq) and PICRUSt2 estimated microbial genes. The Microbiome-Induced Nitric Oxide Enrichment Score (MINES) was calculated as a ratio of microbial gene abundances representing enhanced net capacity for NO generation. Adjusted multivariable linear models regressed cardiometabolic risk biomarkers (HbA1c, glucose, insulin, insulin resistance (HOMA-IR), blood pressure) on nitrate intake and MINES together with a MINES × nitrate intake interaction term. RESULTS: Mean nitrate intake was 190 ± 171 mg/day. Significant interactions of MINES and nitrate intake were observed for insulin and HOMA-IR (p < 0.05). Among participants with a low MINES, higher nitrate intake was associated with lower HOMA-IR (1.2 1.1-1.4 vs. 1.5 1.3-1.6; p = 0.002), but levels were similar in those with high MINES (p = 0.84). CONCLUSIONS: A biomarker of higher microbial NO-generating capacity in subgingival plaque is associated with lower insulin and insulin resistance among individuals with lower dietary nitrate intake. Future trials evaluating the cardiometabolic benefits of nitrate-rich diets should incorporate measures of the entire oral microbiome.