The impact of the oral microbiome on pulmonary function among people with HIV in Botswana - ABSTRACT Chronic obstructive pulmonary disease (COPD) affects 300 million people and is the third leading cause of death globally, with >80% of these deaths occurring in low- and middle-income countries (LMICs). LMICs, particularly those in sub-Saharan Africa, are also home to over two thirds of the global population of people with HIV (PWH). HIV increases the risk of COPD and COPD-associated mortality, but the mechanisms underlying this risk are incompletely understood. Elucidating mechanisms that lead to COPD in PWH in LMICs is particularly important, as an estimated one third of COPD cases in LMICs are not attributable to known COPD risk factors. Systemic inflammation is associated with disease severity in COPD and impaired lung function in PWH. Similarly, the oral microbiome is altered in patients with COPD, and data from the US identified a link between oral microbiome composition and COPD in PWH. However, no studies of the oral microbiome and systemic inflammation have been conducted in sub-Saharan Africa, where PWH are exposed to distinct environmental, occupational, and behavioral factors that affect their risk of COPD and alter their oral microbiomes. This career development award will directly address this knowledge gap. The overall objectives of the current application are to 1) identify associations between the oral microbiome, systemic inflammation, and COPD among PWH in Botswana and 2) develop the skillset needed to pursue an independent career in respiratory microbiome research. To accomplish our objectives, we will recruit 500 adults with chronic respiratory symptoms (250 PWH, 250 HIV-uninfected) from public clinics in Botswana and conduct serial pulmonary function testing and oral specimen collection on a stratified random sample of 200 adults every six months for 24 months. We hypothesize that alterations of the oral microbiome will associate with lung function decline, inflammation, and COPD in PWH. I am uniquely qualified to lead this project given my clinical training in pulmonary medicine, formalized training in research methods via a Master of Science in Global Health, and commitment to research spanning nearly two decades. Furthermore, I am integrated into the clinical and research infrastructure in Botswana and have gathered valuable preliminary microbiome and spirometry data to prepare for this award. To achieve my long-term goal of leveraging host-microbiome interactions to reduce the development and progression of COPD in highly affected populations like PWH, I am seeking further skill development in microbiome science and the conduct of longitudinal clinical research. In addition to preparing me for a career as an independent clinician scientist, this proposal will address multiple National Institutes of Health HIV/AIDS research priorities, including increasing our understanding of HIV-related comorbidities. Lastly, our findings could be used to validate microbiome-based biomarkers for COPD and will contribute to the equitable development of novel COPD therapies by generating data from a population overrepresented in global COPD mortality but underrepresented in current COPD and microbiome research.
