Desvarieux, Moı̈se

ABSTRACT 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.

Background: Dietary nitrate consumption is associated with cardiometabolic health in many but not all studies. The enterosalivary nitrate-nitrite-nitric oxide (NO 3 - NO 2 - NO) pathway requires the oral microbiome for NO production (a signaling molecule beneficial to cardiometabolic health) following nitrate intake. We hypothesize that the oral microbiome modifies the cardiometabolic benefits of nitrate intake. Methods: We analyzed cross-sectional data from 657 ORGINS participants. Dietary nitrate intakes and alternative healthy eating index (AHEI) scores were calculated from food frequency questionnaire responses and a US food database. Subgingival 16S rRNA microbial genes (Illumina, MiSeq) were sequenced, and PICRUSt2 estimated metagenomic content. The Microbiome Induced Nitric oxide Enrichment Score (MINES) was calculated as a microbial gene abundance ratio representing enhanced net capacity for NO generation. Cardiometabolic biomarker (systolic and diastolic blood pressure, HbA1C, glucose, insulin, and HOMA-IR) Z-scores were averaged to form a cardiometabolic Z-score (CMZ). Adjusted multivariable linear models regressed CMZ and individual Z-scores on nitrate intake tertiles. Results: Participants were mean age 31±9, 72% female, 31% White, 14% Black, and 28% Hispanic. Mean nitrate intake was 189±171 mg/day. Higher nitrate intake was significantly associated with lower CMZ, glucose, insulin, and HOMA-IR. Mean CMZ(SE) across dietary nitrate tertiles were 0.53(0.30), 0.35(0.31), and -0.11(0.30), p for trend=0.04; findings were attenuated after adjustment for AHEI (p for trend=0.12). In subgroup analysis by MINES level, higher nitrate intake was only associated with lower cardiometabolic biomarker levels among participants with a <median MINES even after AHEI adjustment (Table). Conclusion: Higher dietary nitrate intake was associated with lower cardiometabolic risk biomarker levels only among those with reduced potential for oral microbiome-dependent NO generation.

AbstractAimWe investigated whether periodontal measures are cross‐sectionally associated with prediabetes and cardiometabolic biomarkers among non‐diabetic younger adults.Materials and MethodsOne thousand seventy‐one participants (mean age = 32.2 years [SE = 0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full‐mouth clinical attachment loss (fm‐CAL), probing depth (fm‐PD) and bleeding on probing were ascertained. Interproximal CAL (i‐CAL) and probing depths (i‐PD) served as our primary exposures. Glucose, HbA1c, insulin and insulin resistance (HOMA‐IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR [95% CI]) and mean [SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression.ResultsPrevalence of prediabetes was 12.5%. Fully adjusted prediabetes PR in Tertiles 3 versus 1 of mean i‐CAL was 2.42 (1.77, 3.08). Fully adjusted fasting glucose estimates across i‐CAL tertiles were 83.29 [0.43], 84.31 [0.37], 86.48 [0.46]; p for trend <.01. Greater percent of sites with i‐PD ≥3 mm showed elevated natural‐log‐HOMA‐IR after adjustment (0%–12% of sites = 0.33 [0.03], 13%–26% of sites = 0.39 [0.03], ≥27% of sites = 0.42 [0.03]; p for trend = .04).Conclusionsi‐CAL (vs. fm‐CAL) was associated with elevated fasting glucose and prediabetes, whereas i‐PD (vs. fm‐PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes.