RSV infection in neonatal mice and gastrointestinal microbiome alteration contribute to allergic predisposition.

Abstract

Severe respiratory syncytial virus (RSV) infection during infancy is associated with a 2 to 4-fold increased risk for the development of wheezing and asthma. Recent studies have implicated microbiome changes, either within the lung or gut, during early life can also affect the development of pulmonary disease. Our studies demonstrate long-term gastrointestinal and lung microbiome changes following early life (EL) RSV infection. To determine the respective roles of ELRSV infection and the gut microbiome, we performed germ-free neonatal infection and microbiome colonization using a microbiome from an uninfected animal followed by cockroach allergen (CRA)-induced asthma 4 weeks later. Germ-free animals with ELRSV infection displayed increased airway disease that was diminished by microbiome colonization, including airway hyperreactivity (AHR), mucus, and eosinophil infiltration. To address the role of virus induced gastrointestinal microbiome alterations, we utilized GF mice conventionalized with RSV-associated or naive microbiomes followed by CRA-induced disease. Transfer of neonatal microbiome taken during acute RSV infection did not alter the allergic response to CRA. However, the transfer of a naive adult microbiome conferred protection from enhanced AHR in response to CRA whereas an RSV associated microbiome did not. Taken together, our data indicate that microbiome alteration and early life RSV infection both contribute to allergic predisposition.