Human Virome Characterization Center for the Oral-Gut-Brain Axis - Overall-Project Summary/Abstract The NIH Human Microbiome Project has redefined our understanding of the human bacteriome, opening new avenues of research in the biomedical and behavioral sciences and improving healthcare delivery. However, the human virome remains largely unexplored. In response to this gap, the NIH Human Virome Program (HVP) offers the opportunity to uncover the spectrum of “healthy” viromes across the lifespan, facilitating identification of alterations associated with disease and further advancing biomedical research and healthcare delivery. Toward this goal, we propose to establish this Human Virome Characterization Center (HVCC) for the Oral–Gut–Brain Axis, a known functional unit with a central role in human health. Informed by our team’s long-standing expertise studying these organs and their interconnected physiology, we will create an organizational hub for virome study, leveraging multiple unique and diverse cohorts. Our goal is to identify and characterize the viruses comprising the human virome across the oral–gut–brain axis, providing accurate estimates of its richness and complexity in healthy cohorts across the life/healthspan. In support of this goal, we bring together investigators at several institutions, including UCLA, Baylor College of Medicine, Mayo Clinic, Penn State, USC, UCSD, NIH/NIDCR, with broad experience successfully guiding large NIH programs. We will establish five interacting Cores— Administrative, Biospecimen Collection, Biospecimen Analysis, Data Analysis and Submission, and Ethical, Legal, and Social Implications (ELSI)—that will work together to identify the viromes in numerous patient cohorts diverse in age, race/ethnicity, each derived from the three target organs. Our Cores have interdisciplinary expertise across key areas, including virome/microbiome sequencing, biomedical informatics/data science, and patient recruitment/tissue banking, and will be tasked with handling multiple data types (virome/microbiome, genomic, neuroimaging) to support the broad aims of our HVCC. The Biospecimen Collection Core will leverage prospective cohorts and retrospective biospecimen banks at UCLA, Mayo Clinic, and NIH/NIDCR, as well as several future cohort opportunities (All of US, Together for Change, AIIMS/India). Our Biospecimen Analysis Core will use cutting-edge technologies to sequence the viromes in our biospecimens, and our Data Analysis and Submission Core will analyze the data we collect using innovative bioinformatics, data science, and machine- learning tools to uncover clinical, physiologic, and genetic interactions that shape the human virome. The ELSI Core will provide policies and guidance and conduct original research to explore the ELSI of this work. The Administrative Core will bridge the patient cohort teams with the supporting Cores to ensure seamless operation and coordination with the broader HVP. Our Cores are designed to maximize the integration and sharing of ideas through dynamic, contemporary communication methods, promoting refinement and dissemination of best practices between our group and the wider scientific community. In doing so, this HVCC will provide a unified framework to broadly advance our understanding of the oral–gut–brain virome toward improving human health.
