Determining the Impact of Metabolic Syndrome on the Oral Microbiome and Periodontal Health Using a Longitudinal Systems Biology Approach

Metabolic Syndrome (MetS) affects over one-third of U.S. adults and is closely linked with oral health issues, particularly periodontitis. The bidirectional relationship between MetS and periodontitis exacerbates both conditions, but the underlying mechanisms remain unclear. Our preliminary R03 data indicate that MetS alters the oral microbiome, creating an ‘at-risk-for-harm’ environment even in the absence of clinical periodontal disease. This project aims to elucidate these mechanisms through a longitudinal systems biology approach, focusing on how restoring metabolic health impacts the functional oral ecosystem. We hypothesize that improved metabolic health will shift the oral microbiome towards a eubiotic state, reduce pathogenic strains, and alter the metabolome to a less inflammatory profile. We test our hypothesis in the following specific aims. In Specific Aim 1: We will track the oral microbiome's temporal dynamics in MetS and Metabolically Healthy Obese (MHO) cohorts undergoing lifestyle or surgical interventions, comparing them with healthy and periodontal disease cohorts. In Specific Aim 2: We will analyze changes in the oral metabolome post-metabolic intervention using advanced mass spectrometry techniques. In Specific Aim 3: We aim to identify and validate oral biomarkers and risk indicators linked to metabolic health improvements. This study will use a causal mediation framework to explore direct and indirect effects, providing crucial insights into the MetS-periodontal health relationship and aiding in the development of prognostic biomarkers and risk indicators in the future. Project Number: 1R01DE034679-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: Sukirth Ganesan | Institution: UNIVERSITY OF IOWA, IOWA CITY, IA | Award Amount: $699,184 | Activity Code: R01 | Study Section: Oral, Dental and Craniofacial Sciences Study Section[ODCS] View on NIH RePORTER: https://reporter.nih.gov/project-details/11296416