Salivary metabolomics in the family environment: A large-scale study investigating oral metabolomes in children and their parental caregivers

Human metabolism is complex and dynamic, and is impacted by genetics, diet, health, and countless inputs from the environment. Beyond the genetics shared by family members, cohabitation leads to shared microbial and environmental exposures. Furthermore, metabolism is affected by factors such as inflammation, environmental tobacco smoke (ETS) exposure, metabolic regulation, and exposure to heavy metals. Metabolomics represents a useful analytical method to assay the metabolism of individuals to find potential biomarkers for metabolic conditions that may not be phenotypically obvious or represent unknown physiological processes. As such, we applied untargeted LCMS metabolomics to archived saliva samples from a racially diverse group of elementary school-aged children and their caregivers collected during the "90-month" assessment of the Family Life Project. We assayed a total of 1,425 saliva samples of which 1,344 were paired into 672 caregiver/child dyads. We compared the metabolomes of children (N = 719) and caregivers (N = 706) within and between homes, performed population-wide "metabotype" analyses, and measured associations between metabolites and salivary biomeasures of inflammation, antioxidant potential, ETS exposure, metabolic regulation, and heavy metals. Dyadic analyses revealed that children and their caregivers have largely similar salivary metabolomes. Although there were differences between the dyads at the individual levels of analysis, dyad explained most (62%) of the metabolome variation. At a population level of analysis, our data clustered into two large groups, indicating that people likely share most of their metabolomes, but that there are distinct "metabotypes" across large sample sets. Lastly, individual differences in several metabolites - which were putative oxidative damage-associated or pathological markers - were significantly correlated with salivary measures indexing inflammation, antioxidant potential, ETS exposure, metabolic regulation, and heavy metals. Implications of the effects of family environment on metabolomic variation at the population, dyadic, and individual levels of analyses for health and human development are discussed. ### Competing Interest Statement In the interest of full disclosure, DAG is founder and Chief Scientific and Strategy Advisor at Salimetrics LLC and Salivabio LLC. These relationships are managed by the policies of the committees on conflict of interest at the Johns Hopkins University School of Medicine and the University of California, Irvine. No other authors have conflicts to disclose.