The respiratory microbiome and its role in the host response to wood smoke - PROJECT SUMMARY/ABSTRACT The respiratory microbiome was reported for the first time in 2010. Since then, various studies have shown that the microorganisms in the respiratory tract influence respiratory health, as changes in the respiratory microbiome have been associated with airway inflammation and various respiratory diseases, like asthma and allergic rhinitis. While studies have reported dysbiosis of the microbiome with exposure to general pollutants like particulate matter, the impact of climate change-dependent pollutants like wood smoke is currently unknown yet is likely to have significant health implications. As wood smoke exposure events are growing worldwide due to wildfires, it is critical that we learn more about the respiratory response to this exposure. Therefore, the overall objective of this proposal is to characterize the structural and functional changes of the respiratory microbiota and its metabolome after wood smoke exposure and identify the mechanism(s) by which the respiratory microbiota and its metabolome modulate the host response to this exposure. The central hypothesis of this project is that the respiratory microbiome is a significant component of the host response to wood smoke via metabolite-driven host-microbiome interactions. Therefore, my specific aims will first (Aim 1) characterize the in vivo effects of wood smoke on the respiratory microbiota and metabolome individually, followed by an innovative multi-omics approach that integrates respiratory microbiome and metabolomics data to determine interactions. My second aim (Aim 2) focuses on identifying the microbe-derived metabolites and metabolite-driven mechanisms that modulate the host response to wood smoke. Here, I will study the in vitro effect of this exposure on the individual components of host-microbiota interactions and their metabolite-driven crosstalk. The results of this proposal will be significant as they will demonstrate for the first time that the respiratory microbiota has an active role in the host response to wood smoke via metabolites, highlighting the importance of considering the respiratory microbiome in inhalational toxicology. Furthermore, these results will identify microorganisms and microorganism-derived metabolites with potential therapeutic and prophylactic properties against wood smoke- induced respiratory adverse health effects. Notably, this project will provide multiple training opportunities in microbiome analysis, metabolomics, and advanced computational analyses, such as multi-omics data integration and machine learning, significantly advancing my goal to become an independent scientist.
