Integrative multi-omics analysis reveals oral microbiome-metabolome signatures of obesity

Obesity is a leading global health challenge and risk factor for cardiometabolic disorders, driven in part by industrialization and low-fiber, ultra-processed diets. While the gut microbiome has been implicated in obesity, the contribution of the oral microbiome-the body's second largest microbial ecosystem-remains underexplored. We analyze a prospective cohort of 628 Emirati adults, including multi-omics profiling of 97 obese individuals and 95 matched controls, generating the most comprehensive oral microbiome analysis to date. Obese participants show altered microbial diversity, composition, functions, and metabolites with enrichment of proinflammatory Streptococcus parasanguinis, Actinomyces oris, and lactate-producing Oribacterium sinus. Pathways for carbohydrate metabolism, histidine degradation, and obesogenic metabolites are upregulated, whereas B-vitamin and heme biosynthesis are depleted. Corresponding metabolites-including lactate, histidine derivatives, choline, uridine, and uracil-are elevated and correlate with obesity-linked cardiometabolic markers. These findings reveal mechanistic oral microbiome-metabolite shifts, highlighting oral microbiome-host interactions as novel targets for obesity prevention and intervention.