Associations between obesity, periodontal inflammation, subgingival microflora and salivary flow rate

Abstract: Obesity is a large health problem and is associated with increased risk of diabetes type II, cardiovascular disease as well as implicated in a wide range of gastrointestinal disorders such as Crohn’s disease and subclinical bowel inflammation. Obesity is also associated with enhanced prevalence of chronic periodontitis in adults. The overall aim of this thesis was to investigate if and how the low grade chronic inflammation accompanying obesity affects oral health in adolescents. More specifically: Study I was designed to investigate whether obesity in adolescence is associated with periodontal risk indicators or disease. Study II tests the hypothesis whether subgingival microbiological colonization is linked with obesity in adolescents. Study III was designed to investigate whether periodontal disease in terms of pathological periodontal pockets is associated with raised blood pressure and other risk markers for cardiovascular disease (CVD) in obese adolescents. Study IV investigates the level of inflammatory markers in saliva and their association to salivary flow rate in obese adolescents. Obese adolescents (Studies I-IV) and normal weight subjects (Studies I, II and IV) within the age range 11-18 years were examined with respect to visible plaque index (VPI%), gingival inflammation (bleeding on probing (BOP%)), occurrence of pathological pockets exceeding or equal to 4mm (PD≥ 4mm). The subjects answered a questionnaire concerning medical conditions, oral hygiene habits, smoking habits and sociodemographic background. Body mass index (BMI) was calculated and adjusted for age and gender (BMI-sds). Samples of gingival crevicular fluid (GCF), subgingival plaque, blood serum and stimulated whole saliva were collected and analyzed. Systolic and diastolic blood pressures were measured and registered. The flow rate of stimulated whole saliva (ml/min) was determined. Obese subjects exhibited more BOP> 25% (P< 0.001) and more PD≥ 4mm (P<0.001) than the normal weight subjects. Higher levels of Interleukin (IL)-1β (P< 0.001) and IL-8 (P= 0.002) were measured in GCF from obese subjects compared with the controls. In a multivariate logistic regression analysis, BMI-sds (P= 0.03; Odds Ratio (OR) = 1.87) was significantly associated with the occurrence of PD≥ 4mm after adjusting for BOP> 25% and subgingival calculus. The sum of bacterial cells in subgingival biofilm was significantly associated with obesity (P< 0.001). The link between sum of bacterial cells and obesity was not confounded by any of the studied variables (chronic disease, education, VPI%, BOP%, flow rate of whole saliva, or meal frequency). Totally 23 bacterial species were present in approximately three-fold higher amounts, on average, in obese subjects compared with normal weight controls. Of the Proteobacteria phylum, Campylobacter rectus and Neisseria mucosa were present in six-fold higher amounts among obese subjects. Obese adolescents with PD≥ 4mm had higher diastolic blood pressure (P= 0.008), higher levels of IL-6 (P< 0.001), Leptin (P= 0.018), Macrophage Chemoattractant Protein-1 (MCP-1) (P= 0.049) and thyroid stimulating hormone (TSH) (P= 0.004) in blood serum compared with subjects without PD≥ 4mm. The bivariate linear regression analysis demonstrated that PD≥ 4mm (P= 0.008) and systolic blood pressure (P< 0.001) were significantly associated with the dependent variable “diastolic blood pressure”. The association between PD≥ 4mm and diastolic blood pressure remained significant (P= 0.006) even after adjusting for the potential confounders BMI-sds, age, gender, mother’s country of birth, BOP> 25%, IL-6, IL-8, Leptin, MCP-1, TSH and total cholesterol in the multiple regression analysis. The obese subjects exhibited lower mean value of flow rate of stimulated whole saliva, 1.3 vs. 2.0 ml/min (P< 0.001), compared to their normal weight counterparts. Obese adolescents had higher levels of salivary Insulin (p< 0.001), Leptin (p= 0.005), C-reactive protein (CRP) (p= 0.002) and Interferon (INF)-γ (p= 0.011). Low stimulated whole saliva flow rate (< 1.5ml/min) was significantly associated with BMI-sds (p< 0.001), as well as the biomarkers IL-1β (p= 0.026) and IL-8 (p= 0.013) and the associations were not confounded by age, gender, chronic disease, drugs affecting salivary flow, PD≥ 4mm and protein content in saliva. In conclusion, obesity in adolescents is associated with increased periodontal inflammation, increased subgingival microbiological colonization and low flow rate of whole saliva. In addition, the presence of pathological periodontal pockets in obese adolescents is associated with raised diastolic blood pressure. The results call for collaboration between pediatric dentists and medical physicians in preventing obesity development and its associated disorders.