A single respiratory tract infection early in life reroutes healthy microbiome development and affects adult metabolism in a preclinical animal model

SUMMARY

In adult animals, acute viral infections only temporarily alter the composition of both respiratory and intestinal commensal microbiota, potentially due to the intrinsic stability of this microbial ecosystem. In stark contrast, commensal bacterial communities are rather vulnerable to perturbation in infancy. Animal models proved that disruption of a balanced microbiota development e.g., by antibiotics treatment early in life, increases the probability for metabolic disorders in adults. Importantly, infancy is also a phase in life with high incidence of acute infections. The authors of this article, published in npj Biofilms and Microbiomes and led by GCIR member Professor Mirco Schmolke, postulated that acute viral infections in early life might pose a similarly severe perturbation and permanently shape microbiota composition with long-term physiological consequences for the adult host. As a proof of concept, they infected infant mice with a sub-lethal dose of influenza A virus. They determined microbiota composition up to early adulthood (63 days) from small intestine by 16S rRNA gene-specific next-generation sequencing. Infected mice underwent long-lasting changes in microbiota composition, associated with increase in fat mass. High-fat-high-glucose diet promoted this effect while co-housing with mock-treated animals overwrote the weight gain. Their data suggest that in the critical phase of infancy even a single silent viral infection could cast a long shadow and cause long-term microbiota perturbations, affecting adult host physiology.

Read full article: https://doi.org/10.1038/s41522-022-00315-x

Why is this study important?

Antibiotic administration in infants leads to altered microbial ecology and results in a long-term dysbiotic state and increased incidence of obesity and type II diabetes in both humans and mice.

Childhood is also a phase of human life with an increased incidence of acute infections. Based on previous experiments, the authors of this work had already shown that an established and robust adult gut microbiota returns to baseline after undergoing qualitative and quantitative changes following acute infection, for example with influenza A virus.

Here, they hypothesised that a single acute infection event may be sufficient to permanently alter the commensal bacterial composition, when it occurs at a dynamic and vulnerable stage of microbiota development. Therefore, they demonstrated that infant mice infected with influenza A virus are at risk of long-lasting qualitative and quantitative changes in gut microbiota composition and overall growth of the animal.

Human association studies would be needed to test whether severe childhood infections can have a lasting impact on microbiota composition and host physiology.

This project was funded by the Swiss National Fund.

News