Abstract

Introduction: Chronic inflammation is hypothesized as a mechanism linking microbial exposures to insulin resistance. We investigated the association between periodontal microbiota, systemic inflammation and insulin resistance among diabetes-free adults. Hypotheses: We hypothesized that subgingival microbial signatures would be related to both inflammatory phenotype and measures of insulin resistance and that there would be evidence of mediation by inflammatory markers. 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). 304 subgingival plaque samples (2 per participant) were analyzed using the Human Oral Microbe Identification Microarray (HOMIM) to measure the relative abundances of 379 taxa from eight different phyla. C-reactive protein, interleukin-6, tumor necrosis factor-α and adiponectin were assessed from venous blood and their z-scores were summed to create an inflammatory score (IS). Fasting glucose and insulin levels defined insulin resistance via the HOMA-IR. Associations between the subgingival microbiota and both inflammation and insulin resistance were explored using multivariable linear regression models adjusted for cardiometabolic risk factors; mediation analyses assessed the proportion of the association explained by inflammation. Results: The IS was inversely associated with the relative abundance of Actinobacteria and Proteobacteria and positively associated with Firmicutes and TM7 (all p-values<0.05). The IS was positively associated with glucose, insulin and HOMA-IR (all p<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). 18 individual taxa were associated with inflammation (p<0.05) and 22 with insulin resistance (p<0.05). Conclusion: Subgingival microbial community structure and membership were related to systemic inflammation and insulin resistance in a sample of diabetes-free adults.

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