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Updated: May 30, 2026
Probiotic Studies in Neonatal Mice Using Gavage
Published on: January 27, 2019
RSV infection in neonatal mice and gastrointestinal microbiome alteration contribute to allergic predisposition
Alexander D Ethridge1, Kazuma Yagi2, Llilian Arzola Martínez2
1Immunology Graduate Program, Rackham Graduate School, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
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.
Insights
Early life respiratory syncytial virus (RSV) infection alters the gut microbiome, increasing asthma risk. Microbiome restoration can mitigate this, highlighting its role in allergic disease development.
Area of Science:
- Microbiology
- Immunology
- Pulmonology
Background:
- Infant respiratory syncytial virus (RSV) infection elevates the risk of developing wheezing and asthma.
- Early-life microbiome alterations in the lung or gut are increasingly linked to pulmonary disease development.
- RSV infection in early life causes long-term changes in both gastrointestinal and lung microbiomes.
Purpose of the Study:
- To investigate the distinct contributions of early life (EL) RSV infection and gut microbiome status to allergic disease.
- To determine if EL RSV infection or subsequent gut microbiome alterations drive increased susceptibility to asthma.
Main Methods:
- Germ-free neonatal mice were infected with RSV and subsequently colonized with specific microbiomes before cockroach allergen (CRA)-induced asthma.
- Mice were colonized with either an RSV-associated or a naive adult microbiome after RSV infection and then exposed to CRA.
- Airway hyperreactivity (AHR), mucus production, and eosinophil infiltration were assessed as measures of allergic airway disease.
Main Results:
- EL RSV infection in germ-free animals led to increased airway disease, which was reduced by microbiome colonization.
- Transferring a naive adult microbiome protected against enhanced AHR from CRA exposure.
- Transferring an RSV-associated neonatal microbiome did not protect against CRA-induced allergic responses.
Conclusions:
- Both early life RSV infection and associated microbiome alterations contribute to allergic predisposition.
- Microbiome restoration can ameliorate RSV-induced increases in airway disease.
- The composition of the gut microbiome plays a critical role in modulating the immune response to allergens.
