An emerging understanding of the natural history of rheumatic disease where a ‘pre-disease’ state can be identified has led to completed prevention studies in several rheumatic and autoimmune diseases (e.g. type 1 diabetes, rheumatoid arthritis), with many other trials underway. The emergence of potential prevention strategies in rheumatic and autoimmune diseases highlights the importance of fully understanding the mechanisms underlying the development of these diseases, from their initiation with being positive for a predictive biomarker yet without target organ involvement through to the phase(s) of clinically-apparent disease and extensive organ damage. Importantly, as a result of research advances over the past several years, including a number made by members of this University of Colorado (CU) Rheumatic Disease Research Resource Center (RDRRC) proposal, a hypothesis now exists for a key role of chronic inflammation and dysbiosis within the mucosal immune system as a catalyst for both the initial break in self-tolerance in asymptomatic individuals as well as a continued driver to clinical disease development and increasing target organ damage. Exploration of this hypothesis across rheumatic and autoimmune diseases through multiple evolving stages of disease, and the integration of multiple sites within the body (e.g. blood, mucosal sites, and joints), requires special skill sets in study design, assessments such as subject-reported outcomes (e.g. pain, well-being) and environmental exposures (e.g. dietary intake, tobacco use), biospecimen collection and processing (including blood and mucosal samples), and analyses. To address these important issues, the role of the RDRRC Resource Core 1: Population and Data Sciences is to provide advisory support for high-quality studies in rheumatic disease as well as unique access to banked data and biospecimens as well as ‘living biorepositories’ of informative subjects. These activities will facilitate research into the natural history of rheumatic disease around the role of mucosal processes. Importantly, the Core’s activities are also expected to recruit new investigators into this area by providing the support and materials necessary to facilitate their awareness and research opportunities. In aggregate, these activities as well as the other RDRRC activities should advance the field in terms of understanding disease pathogenesis, diagnosis and treatment, as well as actionable prevention of rheumatic disease.