Microbiome in Asthma Induced by Environmental Particle Exposure
Microbial dysbiosis in the gut and the lung is increasingly being associated with the incidence and severity of asthma, however causality studies are lacking. We have adapted a mouse model that focuses on the onset of allergic asthma early in life after an in-utero exposure to environmental particles to study how pollution-driven changes to microbiome may lead to the asthma onset. In this model, we have shown that maternal exposures to allergen or particulate matter, e.g. concentrated urban air particles (CAP), diesel exhaust particles (DEP) and titanium dioxide particles (TiO2), trigger increased asthma risk in several generations of the offspring.
Humans are widely exposed to these particulates, especially in urban and industrial settings, where the incidence of asthma is also higher. We found that the increased ‘preparedness’ for asthma in these neonates is associated with DNA methylation changes in key immune cells – dendritic cells that are essential in asthma origin. Important unanswered questions are why these epigenetic changes occur, and whether there is a causative link to the aberrant microbiome seen in asthma.
We hypothesize that in utero exposures to particles alter the microbiome of the pregnant mice and their offspring, which then signals to the immune cells in a way that predisposes the offspring to allergy. We postulate two, potentially interconnected, mechanisms in asthma onset: epigenetics and the microbiome. Both the epigenetic alterations in immune cells and the dysbiosis in the gut and lung have been linked to asthma in humans and mouse models but causality studies are lacking. The proposed research addresses this gap in knowledge in a study designed to test basic mechanisms of relatively common environmental exposures.
Funding for this project provided by National Institutes of Health, National Institute of Environmental Health Sciences through grant number R01ES030227.
Alexey Fedulov, MD, PhD