Dynamics of the upper airway microbiome in the pathogenesis of asthma-associated persistent wheeze in preschool children

Teo, Shu Mei; Tang, Howard HF; Mok, Danny; Judd, Louise M; Watts, Stephen C; Pham, Kym; Holt, Barbara J.; Kusel, Merci; Serralha, Michael; Troy, Niamh; Bochkov, Yury A; Grindle, Kristine; Lemanske, Robert F; Johnston, Sebastian L; Gern, James E; Sly, Peter D; Holt, Patrick G; Holt, Kathryn E; Inouye, Michael

Repeated cycles of infection-associated lower airway inflammation drives the pathogenesis of persistent wheezing disease in children. Tracking these events across a birth cohort during their first five years, we demonstrate that >80% of infectious events indeed involve viral pathogens, but are accompanied by a shift in the nasopharyngeal microbiome (NPM) towards dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change in NPM frequently precedes the appearance of viral pathogens and acute symptoms. In non-sensitized children these events are associated only with “transient wheeze” that resolves after age three. In contrast, in children developing early allergic sensitization, they are associated with ensuing development of persistent wheeze, which is the hallmark of the asthma phenotype. This suggests underlying pathogenic interactions between allergic sensitization and antibacterial mechanisms.