The subgingival microbiome, systemic inflammation and insulin resistance: The Oral Infections, Glucose Intolerance and Insulin Resistance Study

Abstract

Background: Inflammation might link microbial exposures to insulin resistance. We investigated the cross-sectional association between periodontal microbiota, inflammation and insulin resistance.

Methods: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 152 diabetes-free adults (77% female) aged 20-55 years (mean = 34 ± 10). Three hundred and four subgingival plaque samples were analysed using the Human Oral Microbe Identification Microarray to measure the relative abundances of 379 taxa. C-reactive protein, interleukin-6, tumour necrosis factor-α and adiponectin were assessed from venous blood and their z-scores were summed to create an inflammatory score (IS). Insulin resistance was defined via the HOMA-IR. Associations between the microbiota and both inflammation and HOMA-IR were explored using multivariable linear regressions; mediation analyses assessed the proportion of the association explained by inflammation.

Results: The IS was inversely associated with Actinobacteria and Proteobacteria and positively associated with Firmicutes and TM7 (p-values < 0.05). Proteobacteria levels were associated with insulin resistance (p < 0.05). Inflammation explained 30-98% of the observed associations between levels of Actinobacteria, Proteobacteria or Firmicutes and insulin resistance (p-values < 0.05). Eighteen individual taxa were associated with inflammation (p < 0.05) and 22 with insulin resistance (p < 0.05). No findings for individual taxa met Bonferroni-adjusted statistical significance.

Conclusion: Bacterial measures were related to inflammation and insulin resistance among diabetes-free adults.

Keywords: C-reactive protein; adiponectin; diabetes; inflammation; insulin resistance; interleukin-6; microbiome; microbiota; periodontal; tumour necrosis factor-α.

Figure 1

Distribution of the 121 subgingival bacterial taxa detected in at least 20% of subjects (a) and 9 bacterial phyla (b) among n=152 men and women aged 18 – 55 years enrolled in The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) 2011 – 2013.

Figure 1

Distribution of the 121 subgingival bacterial taxa detected in at least 20% of subjects (a) and 9 bacterial phyla (b) among n=152 men and women aged 18 – 55 years enrolled in The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) 2011 – 2013.

Figure 2

Mean adjusted glucose, insulin and HOMA-IR levels across tertiles of four inflammatory mediators, C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) and adiponectin, and an inflammatory score based on the sum of the z-scores of the aforementioned mediators. Adjusted for age, sex, race/ethnicity, education, smoking status and body mass index.

Figure 3

Mean adjusted levels of four inflammatory mediators (C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) and adiponectin), and an inflammatory score (sum of the four standardized inflammatory markers) according to tertiles of the bacterial phyla Actinobacteria, Firmicutes and Proteobacteria. Adjusted for age, sex, race/ethnicity, education, smoking status and body mass index.

Figure 4

Mean adjusted glucose, insulin and HOMA-IR levels across tertiles of the bacterial phyla Actinobacteria, Firmicutes and Proteobacteria. Adjusted for age, sex, race/ethnicity, education, smoking status and body mass index.

Figure 5

Heatmap of multivariable adjusted Spearman correlation coefficients summarizing the association between 25 subgingival taxa (y-axis) and both inflammatory and metabolic biomarkers (x-axis). Axes were organized via unsupervised hierarchical clustering of correlation coefficients. The top 25 strongest correlations coefficients are presented. Color-coding adjacent to the vertical dendrogram corresponds to phylum membership of the taxa for that row of the heatmap: red = Actinobacteria, blue = Bacteroidetes, green = Firmicutes, purple = Fusobacteria, orange = Proteobacteria, yellow = Spirochetes, pink = Tenericutes, brown = Synergistetes, grey = TM7. CRP=C-reactive protein, TNF-α=tumor necrosis factor-α.