Dysbiotic Microbiome–Metabolome Axis in Childhood Obesity and Metabolic Syndrome

The prevalence of childhood metabolic syndrome (MetS) and obesity is rising, with emerging evidence suggesting these conditions negatively affect oral health. However, the underlying molecular determinants are unclear. This study investigated the oral microbiome, inflammatory markers, and metabolites in children with obesity and MetS to explore the interrelationships between systemic disease and oral health. We recruited 76 periodontally healthy, caries-free individuals aged 10 to 17 y into 3 groups: MetS (29), metabolically healthy obesity (MHO) (30), and normal-weight healthy (NWH) controls (17). Unstimulated saliva was collected. Bacterial DNA was isolated, V3–V4 regions amplified, and 16S sequencing performed on the Illumina MiSeq platform. Sequences were annotated against the HOMD database. Multiplex assays quantified adipokines and cytokines, with significance determined by Tukey honestly significant difference. Gas chromatography/mass spectrometry identified metabolite peaks that were annotated against the Small Molecule Pathway Database, with enrichment analysis determining significance. Integrated multiomics analysis was performed using multiblock sparse partial least squares regression discriminant analysis. The MHO and MetS groups demonstrated lower abundances of Streptococcus , Actinomyces , and Schaalia and higher levels of Aggregatibacter , Campylobacter , Alloprevotella , Prevotella , Leptotrichia , and Porphyromonas compared with NWH, despite similar clinical oral status in all cohorts. MetS and MHO also had increased leptin, tumor necrosis factor–α, interleukin (IL)–1β, and IL-15 and decreased adiponectin levels versus NWH. Disease-associated metabolites, including glutamate, cholesterol, isoleucine, tyrosine, phenylalanine, serine, and indoleacetic acid, were significantly enriched in the MetS and MHO groups. Integrated multiomic analysis identified key correlations in the saliva of subjects with metabolic health or disease. Decreases in health-associated species and increases in proinflammatory cytokines and disease-associated metabolites in the saliva of MetS and obese adolescents with clinical oral health indicate an “at-risk” environment, potentially explaining their elevated risk for oral diseases. Increased salivary leptin and decreased adiponectin levels highlight the potential of saliva as a noninvasive biomarker source for childhood MetS.