Effect of gut microbiome transplant from neonates of particle-exposed mothers on the epigenome of dendritic cells

In our model the newborns of asthmatic mother mice or of mothers exposed to air pollutant particles are born with a predisposition to asthma. Gut microbiome of these pups is altered, and the transplant of the pups’ microbiome (GMT) has conferred the asthma predisposition to naïve recipients. We hypothesized that bacteria alter metabolomic profile in the gut, which polarizes the dendritic cells (DC) in the recipient by affecting epigenetic regulation in these key decision-maker cells. Here we examined DNA methylation profiles in the recipient host’s DCs to test the prediction that GMT confers alterations in DNA methylation (not seen with sterilized GMT). Pregnant dams are exposed to concentrated urban air particles (CAP). A fraction of their offspring is tested for asthma predisposition seen as airway inflammation after an intentionally low dose of allergen that remains innocuous in control neonates. Another fraction becomes donors of gut microbiome; after a transplant the recipients are similarly tested. A subset of microbiome transplants is gamma-sterilized prior to instillation into recipients. Hence the 4 groups are: offspring of PBS control mother, offspring of CAP mother, GMT recipients of the material from the offspring of CAP mother, and recipients of sterilized GMT material from the offspring of CAP mother.