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)

Charlene E Goh; Bruno Bohn; Jeanine M Genkinger; Rebecca Molinsky; Sumith Roy; Bruce J Paster; Ching-Yuan Chen; Stephen Johnson; Melana Yuzefpolskaya; Paolo C Colombo; Michael Rosenbaum; Rob Knight; Moïse Desvarieux; Panos N Papapanou; David R Jacobs Jr; Ryan T Demmer

doi:10.1111/jcpe.70084

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)

J Clin Periodontol. 2025 Dec 25. doi: 10.1111/jcpe.70084. Online ahead of print.

Authors

Charlene E Goh¹, Bruno Bohn², Jeanine M Genkinger^{3

4}, Rebecca Molinsky², Sumith Roy³, Bruce J Paster^{5

6}, Ching-Yuan Chen⁷, Stephen Johnson⁸, Melana Yuzefpolskaya⁹, Paolo C Colombo⁹, Michael Rosenbaum¹⁰, Rob Knight^{11

12

13}, Moïse Desvarieux^{3

14}, Panos N Papapanou⁷, David R Jacobs Jr², Ryan T Demmer^{2

3

8}

Affiliations

¹ Faculty of Dentistry, National University of Singapore, Singapore.
² Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
³ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
⁴ Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York, USA.
⁵ The Forsyth Institute, Cambridge, Massachusetts, USA.
⁶ Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
⁷ Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, College of Dental Medicine, Columbia University, New York, New York, USA.
⁸ Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, College of Medicine and Science, Rochester, Minnesota, USA.
⁹ Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York, New York, USA.
¹⁰ Division of Molecular Genetics, Department of Pediatrics and Medicine, Columbia University, New York, New York, USA.
¹¹ Department of Computer Science & Engineering, Jacobs School of Engineering, University of California San Diego, La Jolla, California, USA.
¹² Department of Bioengineering, University of California San Diego, La Jolla, California, USA.
¹³ Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA.
¹⁴ INSERM UMR 1153, Centre de Recherche Epidemiologie et Statistique Paris Sorbonne Cité (CRESS), METHODS Core, Paris, France.

PMID: 41448605
DOI: 10.1111/jcpe.70084

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.

Keywords: cardiometabolic risk factors; diet; epidemiology; microbiome and metagenomics; nitrate(s); oral and systemic health.

Abstract

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