Salivary Metabolomic Signature of Metabolic Syndrome
Objectives: Over a billion people worldwide and more than one-third of the US adult population suffer from Metabolic Syndrome (MetS). MetS is a cluster of the most dangerous heart-attack risk factors such as increased waist circumference (central obesity), blood pressure elevation, low HDL cholesterol, high triglycerides, and hyperglycemia/insulin resistance. Evidence is emerging to show an increase in the severity of periodontitis among MetS individuals. However, the mechanism behind these associations is yet to be validated. Hence, we investigated the end-stage small molecules (metabolites) that are the breakdown products in the oral environment in MetS patients using a cross-section case-control study. Methods: 57 frequency-matched, periodontally healthy adults meeting our inclusion and exclusion criteria were recruited from the University of Iowa Endocrinology Clinics, belonging to three groups: MetS, metabolically benign obesity (MBO), and normal-weight healthy controls (NWH). Unstimulated saliva was collected and stored in -80C. Metabolite peaks identified from Gas Chromatography/Mass spectrometry were annotated against the Small Molecule Pathway Database, and significance determined by enrichment analysis. Results: Principal component analysis revealed the clustering of the metabolites based on metabolic diagnosis. Several tryptophan metabolites that are implied in maintaining mucosa-microbial homeostasis were significantly different between the groups. Eighteen metabolites, including pimelic acid, orotate, cholesterol, DOPA, belonging to aminoacid, carbohydrate, and lipid metabolism, and several periodontitis-associated metabolites such as isoleucine, tyrosine, phenylalanine, serine, oleic acid, butyrate were significantly enriched in MetS and MBO groups when compared to NWH, even in the absence of clinical periodontal disease. Conclusions: MetS and MBO create an at-risk-for-harm environment and increases the risk future periodontal disease as seen by enrichment of periodontitis-associated metabolites in MetS cohort with clinical periodontal health. Identification of metabolite markers denote the potential role of saliva as a biomarker for MetS.