Defining the role of premature infant microbial dysbiosis in mediating immune development and response to infection

Abstract
The gut microbiome plays a critical role in the development of the immune system during the first year of life.
Contact between immune cells and commensal microbes during early life helps to fine-tune this balance, and
early-life perturbations to the microbiome have been linked to later susceptibility to a wide range of health issues,
from gastrointestinal disorders such as irritable bowel syndrome or inflammatory bowel disease, to respiratory
conditions including asthma and chronic obstructive pulmonary disease. The gut microbiome in premature
infants has been well described to be significantly altered, with over-abundance of opportunistic Gram-negative
Enterobacteriaceae. Premature infants are at higher risk for adverse outcomes to respiratory infections such as
respiratory syncytial virus (RSV) due to their immunocompromised state and incomplete lung development. We
hypothesize that the altered state of the premature microbiome affects the ability of the immune system to
effectively deal with infection. Our preliminary data suggest that the altered gut microbiome in premature infants
induces neutrophil-biased immune responses but weaker anti-viral interferon and antibody responses; the
combination of both may contribute to more severe RSV-induced lung injury in premature infants and increase
the risk of asthma in later life. This proposal aims to define the contributions of the altered gut microbiome to the
outcome of RSV infection in preterm infants, and to identify metabolites that might be used to “normalize” the
respiratory immune responses to RSV infection in premature infants and improve their lung functions.

Grant Number: 5F32HD112151-02
NIH Institute/Center: NIH
Principal Investigator: Julia Brown