Human Virome Characterization Center for the Oral-Gut-Brain Axis

Administrative Core - Abstract Knowledge of the bacteria living within our body has grown rapidly over the past decade, spurred in large part by initiatives such as the NIH Human Microbiome Project (HMP). Such collaborative efforts have redefined our understanding of the human bacteriome, opening new avenues of research in the biomedical and behavioral sciences and improving healthcare delivery. In contrast, although viruses are thought to outnumber bacteria 10:1, the human virome remains largely unexplored. The recent coronavirus disease 2019 (COVID-19) pandemic and emerging threats from pathogenic viruses have sounded the collective global alarm regarding our limited knowledge of potential pathogens within the human virome. Moreover, foundational knowledge of what constitutes a healthy human virome and how it affects human health is lacking, representing a significant knowledge gap. The NIH Human Virome Program (HVP) is a grand undertaking that aims to fill this gap by defining all facets of the human virome at different body sites across the life/health span in a broad demographic range of individuals. This program offers a valuable opportunity to advance our understanding of the full spectrum of “healthy” viromes, thereby promoting advances in biomedical research, enabling identification of perturbations associated with disease, and improving our capacity to detect viruses that pose threats to human populations. The proposed Human Virome Characterization Center (HVCC) embraces this opportunity to define the human virome in the oral–gut–brain axis— a recognized functional unit that broadly impacts human health—across the lifespan in diverse cohorts. As the oropharyngeal site is a well-recognized key entry point for pathogenic viruses, defining the healthy virome of the oral–gut–brain axis will help inform a key inflection point for derailing health. Our research and management teams include a multi-PI (MPI) leadership group and five complementary cores: i) Administrative; ii) Biospecimen Collection; iii) Biospecimen Analysis; iv) Data Analysis and Submission; and v) Ethical, Legal, and Social Implications (ELSI). Working together, we will use cutting-edge technologies and bioinformatic tools to elucidate the viromes of unique human oral–gut–brain specimens across the US and broadly share results of these efforts with the public and scientific community. The Administrative Core will organize, lead, and provide monitoring oversight of the HVCC to generate and validate virome sequencing, clinical, and demographic data to define the human virome of the oral–gut–brain axis of diverse populations along the lifespan and health span. The Administrative core will do so by integrating and sharing ideas across our Cores via dynamic, contemporary communication methods; promote refinement and dissemination of best practices between our groups and the scientific community through multiple venues; and evaluate effectiveness of our methods and the HVP initiative. Through these efforts, the Administrative Core will be the central coalescing force propelling our HVCC toward completion of its aims, thereby delivering on the HVP goals and realizing the NIH’s broad vision for the program.