Subgingival Microbiota and Longitudinal Glucose Change: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)

R. T. Demmer, P. Trinh, M. Rosenbaum, G. Li, C. LeDuc, R. Leibel, A. González, R. Knight, B. Paster, P. C. Colombo, M. Desvarieux, P. N. Papapanou, D. R. Jacobs

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Microbial communities along mucosal surfaces throughout the digestive tract are hypothesized as risk factors for impaired glucose regulation and the development of clinical cardiometabolic disease. We investigated whether baseline measures of subgingival microbiota predicted fasting plasma glucose (FPG) longitudinally. The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 230 diabetes-free adults (77% female) aged 20 to 55 y (mean ± SD, 34 ± 10 y) from whom baseline subgingival plaque and longitudinal FPG were measured. DNA was extracted from subgingival plaque, and V3 to V4 regions of the 16S rRNA gene were sequenced. FPG was measured at baseline and again at 2 y; glucose change was defined as follow-up minus baseline. Multivariable linear models regressed 2-y glucose change onto baseline measures of community diversity and abundances of 369 individual taxa. A microbial dysbiosis index (MDI) summarizing top individual taxa associated with glucose change was calculated and used in regression models. Models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and baseline glucose levels. Statistical significance was based on the false discovery rate (FDR; <0.05) or a Bonferroni-corrected P value of 1 × 10-4, derived from the initial 369 hypothesis tests for specific taxa. Mean 2-y FPG change was 1.5 ± 8 mg/dL. Baseline levels of 9 taxa predicted FPG change (all FDR <0.05), among which Stomatobaculum sp oral taxon 097 and Atopobium spp predicted greater FPG change, while Leptotrichia sp oral taxon 498 predicted lesser FPG change (all 3 P values, Bonferroni significant). The MDI explained 6% of variation in longitudinal glucose change (P < 0.001), and baseline glucose levels explained 10% of variation (P < 0.0001). FPG change values ± SE in the third versus first tertile of the MDI were 4.5 ± 0.9 versus 1.6 ± 0.9 (P < 1 × 10-4). Subgingival microbiota predict 2-y glucose change among diabetes-free men and women.

Original languageEnglish (US)
Pages (from-to)1488-1496
Number of pages9
JournalJournal of dental research
Volume98
Issue number13
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Funding Information:
Demmer R.T. 1 2 Trinh P. 3 Rosenbaum M. 4 Li G. 5 LeDuc C. 4 Leibel R. 4 González A. 6 Knight R. 6 Paster B. 7 8 Colombo P.C. 9 Desvarieux M. 2 10 Papapanou P.N. 11 https://orcid.org/0000-0002-7232-0543 Jacobs D.R. Jr 1 1 Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA 2 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA 3 Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA 4 Division of Molecular Genetics, Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA 5 Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA 6 Department of Pediatrics, University of California San Diego, San Diego, CA, USA 7 The Forsyth Institute, Cambridge, MA, USA 8 Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA 9 Division of Cardiology, Department of Medicine, Columbia University, New York, NY, USA 10 Centre de recherche Epidémiologies et Biostatistique, INSERM U1153 Equipe: Méthodes en évaluation thérapeutique des maladies chroniques, Paris, France 11 Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, College of Dental Medicine, Columbia University, New York, NY, USA R.T. Demmer, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South Second Street, Suite 300, Minneapolis, MN 55454, USA. Email: demm0009@umn.edu 10 2019 0022034519881978 © International & American Associations for Dental Research 2019 2019 International & American Associations for Dental Research Microbial communities along mucosal surfaces throughout the digestive tract are hypothesized as risk factors for impaired glucose regulation and the development of clinical cardiometabolic disease. We investigated whether baseline measures of subgingival microbiota predicted fasting plasma glucose (FPG) longitudinally. The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 230 diabetes-free adults (77% female) aged 20 to 55 y (mean ± SD, 34 ± 10 y) from whom baseline subgingival plaque and longitudinal FPG were measured. DNA was extracted from subgingival plaque, and V3 to V4 regions of the 16S rRNA gene were sequenced. FPG was measured at baseline and again at 2 y; glucose change was defined as follow-up minus baseline. Multivariable linear models regressed 2-y glucose change onto baseline measures of community diversity and abundances of 369 individual taxa. A microbial dysbiosis index (MDI) summarizing top individual taxa associated with glucose change was calculated and used in regression models. Models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and baseline glucose levels. Statistical significance was based on the false discovery rate (FDR; <0.05) or a Bonferroni-corrected P value of 1 × 10 -4 , derived from the initial 369 hypothesis tests for specific taxa. Mean 2-y FPG change was 1.5 ± 8 mg/dL. Baseline levels of 9 taxa predicted FPG change (all FDR <0.05), among which Stomatobaculum sp oral taxon 097 and Atopobium spp predicted greater FPG change, while Leptotrichia sp oral taxon 498 predicted lesser FPG change (all 3 P values, Bonferroni significant). The MDI explained 6% of variation in longitudinal glucose change ( P < 0.001), and baseline glucose levels explained 10% of variation ( P < 0.0001). FPG change values ± SE in the third versus first tertile of the MDI were 4.5 ± 0.9 versus 1.6 ± 0.9 ( P < 1 × 10 -4 ). Subgingival microbiota predict 2-y glucose change among diabetes-free men and women. microbiome diabetes risk periodontal epidemiology impaired glucose regulation periodontitis National Institute of Dental and Craniofacial Research https://doi.org/10.13039/100000072 R00 DE018739 National Institute of Dental and Craniofacial Research https://doi.org/10.13039/100000072 R03 027773 National Institute of Dental and Craniofacial Research https://doi.org/10.13039/100000072 R21 DE022422 National Institute of Diabetes and Digestive and Kidney Diseases https://doi.org/10.13039/100000062 R01 102932 edited-state corrected-proof We thank the following individuals for their invaluable contributions to this research: Consuelo Mclaughin, Bennett Batista, and Victor Rivera; Romanita Celenti for her efforts in performing phlebotomy and processing and analyzing plaque samples; and Drs. Aleksandra Zuk, Nidhi Arora, Ashwata Pokherel, Publio Silfa, and Thomas Spinell for their skilled examinations and essential participant engagement. We are profoundly grateful to the ORIGINS participants for their participation in this research. A supplemental appendix to this article is available online. This research was supported by National Institutes of Health grants R00 DE018739, R21 DE022422, and R01 DK 102932 (to R.T. Demmer) and R03 DE 027773 (to G. Li and R.T. Demmer). R.T. Demmer received funding from a Calderone Research Award, Mailman School of Public Health, and R. Leibel received a Pilot and Feasibility Award from the Diabetes and Endocrinology Research Center, College of Physicians and Surgeons (DK-63608). This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. ORCID iD D.R. Jacobs https://orcid.org/0000-0002-7232-0543

Publisher Copyright:
© International & American Associations for Dental Research 2019.

Keywords

  • diabetes risk
  • epidemiology
  • impaired glucose regulation
  • microbiome
  • periodontal
  • periodontitis

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