The human mouth is a gateway for harmful pathogens that can lead to chronic conditions like gum inflammation and caries. The oral cavity is the second most populated microbial habitat in the body. It is densely colonized by over 700 microbe species and harbors an even more diverse bacterial population than the gut. Recent observational studies involving adults have indicated differences in oral microbiome diversity and abundance based on depression. Emerging evidence suggests the role of internal circadian rhythms in the oral microbiome, indicating circadian misalignment could significantly influence its composition and abundance, a phenomenon also affected by sleep loss. These findings hold particular significance for adolescents experiencing depression and undergoing developmental changes in sleep/wake patterns. Most of the work on the taxonomic composition of microbial communities has been descriptive and based on small-scale clinical studies. Research on the associations between the oral microbiome and depression has mainly involved adults. These associations need replication on adolescent and young adult population data. The National Health and Nutrition Examination Survey provides a unique opportunity to replicate these associations as ii contains data on oral microbiome diversity and abundance, sleep and rest-activity rhythms patterns, and depression from a representative sample of adolescents and young adults in the United States (U.S.). Our ultimate goal is to lay the foundation for informing new mechanistic models for adolescent depression through in-depth oral microbiome research. To that end, we have developed the following specific aims: Aim 1. Describe the oral microbiome composition and structure among adolescents (ages 14-17) and young adults (ages 18-24); Aim 2. Compare sleep and circadian rhythm phenotypes on oral microbiome composition and structure; Aim 3. Explore associations between oral microbiome composition and structure and depression; and Aim 4. Explore associations between sleep and circadian rhythm phenotypes, oral microbiome, and depressive symptoms. This proposal addresses the COBRE's goals of examining sleep, circadian rhythms, and adolescent mental health. In the long term, this study will make a meaningful contribution to public health, especially adolescent mental health in the U.S.