Integrating population-wide oral microbiome data to better understand health differences in the United States - Project Summary Oral diseases, such as dental decay, periodontal disease, and tooth loss, are the most common chronic disease in the United States today, and some American adults experience these diseases at up to 3x higher rates, such as Black or Mexican Americans compared to non-Hispanic White Americans. The root cause of these diseases may be linked to the oral microbiota – the diverse communities of bacteria, archaea, viruses, and fungi – that live within the human mouth. We also know that oral microbiota are distinct in people of different backgrounds in the US and that microbiota variation can be mediated by social, behavioral, and economic (SBE) factors. However, there has been little research into how one’s background and SBE factor intersect in driving microbiota variation, or if that variation is linked to oral health differences. This study utilizes 16S ribosomal RNA data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the 2009-10 and 2011-12 survey waves (n=6,224 adults across four ethnicities) to transform the way we understand the roles that oral microbes play in oral health differences in the United States. Our central hypothesis is that the oral microbiome plays a critical role in oral health differences and mediates the relationship between one’s background and traditional SBE factors that have been used to explain these differences. The core scientific objective of this R21 is to disentangle how one’s background and SBE factors shape oral microbial diversity and determine the extent that microbes linked to these factors underpin oral health differences in the US. In Aim 1, we will test how the oral microbiota diversity, composition, and abundance of individual species differs across US backgrounds. In Aim 2, we will test if SBE factors are also linked to oral microbiota variation in the context of one’s background. In Aim 3, we will perform a mediation analysis to understand how specific oral microbes identified in Aim 2 and 2 mediate the relationship with oral health. Understanding if oral microbes contribute to health differences and the factors that guide their presence and abundance is critical for the development of targeted interventions and policies to promote effective oral health therapies in all people. This project is innovative because it will be the first examination of the role of the oral microbiota in population-level oral health differences in the US. Expected outcomes from this project will inform evidence-based public health intervention policies and the foundation to develop mechanistic understandings of the roles microbes play in differential disease outcomes. This information will also be used in the development of microbial therapeutics that target the oral microbiota’s role in oral health differences, thereby promoting effective oral health therapies for all people. This work can also be integrated into studies examining health differences elsewhere in the body, ensuring that US health-based research works to reduce different rates of disease in other areas. This represents an unprecedented opportunity to understand how SBE factors shape oral microbial diversity in people of different backgrounds and contribute to oral health differences.