aMokD, aKusel MMH, aSerralha M, aTroy N, aHoltBJ, aHalesB, aHollamsEM aHoltPG, in collaboration with bSly PD, cGernJE, cBochkov YH, cGrindle L; dJohnstonSL; eTeo SM, ePham K, eWalker ML eHolt KE
aThe Kids Research Institute Australia, University of Western Australia
bQueensland Children’s Medical Research Institute, University of Queensland
cUniversity of Wisconsin School of Medicine and Public Health
dImperial College of London
eDepts of Pathology, Microbiology & Immunology, and Bio21 Institute, University of Melbourne, Australia
Respiratory viral infections during infancy, particularly against a background of early allergic sensitization, have been implicated as risk factors for asthma development. Furthermore, bacterial pathogens may also contribute to pathogenesis although definitive longitudinal data are lacking. We are testing this hypothesis in our Childhood Asthma (CAS) birth cohort study, where we had initially characterized the nasopharyngeal microbiome (NPM) in the children across the first year of life, employing 16S rRNA gene deep sequencing. The resultant data base of >193 million sequence reads was utilized in describing dynamic changes in the NPM associated with viral infections, and linking these with asthma risk at 5 and 10yrs. Analyses are in progress examining the impact of both viral and bacterial infections out to the 5th birthday, including additional viral typing (focusing on rhinovirus subtypes) carried out by our collaborators from the lab of Dr James Gern at University of Wisconsin. Initial findings suggest that the NPM becomes increasingly complex with age, and some organisms (exemplified by Staphylococcus), which were apparent commensals during infancy, appear to take on a more pathogenic role in regards to airways inflammation, at later ages. We are additionally focusing on the role of IgG antibodies to bacterial pathogens, including those of maternal origin, on susceptibility to invasive infections in infancy and beyond. We conclude that dynamic changes in the constituents of the infant NPM contribute independently to driving asthma development, and also play key modulatory role(s) in the parallel asthma causal pathway driven by interactions between virus-driven and allergen-driven inflammatory mechanisms.
Plain language summary: Recent studies have established that both genetic susceptibility and viral infections during early childhood are important drivers of asthma development. It has also been noted that asthmatics’ airways contain different populations of bacteria to non-asthmatics. In this project we are studying how interactions between bacteria and viruses in children's airways promote the development of allergy and asthma.
Funder: National Health and Medical Research Council of Australia.