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- W4313404875 abstract "Abstract The gut microbiome plays a critical role in neonatal immune development; early-life perturbations to the microbiome have been linked to later susceptibility to respiratory conditions, including asthma and chronic obstructive pulmonary disease. Preterm infants are at higher risk for adverse outcomes to respiratory infections such as respiratory syncytial virus (RSV). The microbiome in premature infants is significantly altered, but it remains unclear how this affects lung immune cell development and susceptibility to RSV infection independent of lung immaturity. In this study, we have generated a biorepository of stool specimens from preterm and term infants during the first weeks of life. Metagenomic sequencing studies indicate significant alterations in the gut microbiome between these two groups, including a lack of fiber-fermenting Bacteroides species in preterm infants. Using these stool specimens, we find that the altered gut microbiome in premature infants induces IL-17/neutrophil-biased immune responses but weaker anti-viral interferon responses in the lung, both at steady state and following RSV infection. Mice colonized with preterm infant stool bacteria produced lower levels of neutralizing antibodies against RSV than mice colonized with term infant stool bacteria. Taken together, our findings suggest that the altered gut microbiome in premature infants dysregulates immune cell development in the lung and impairs the infant’s ability to develop long-term immunity against respiratory infections. These findings might be potentially leveraged in the development of gut bacteria-based interventions to improve the development of protective immunity against respiratory viral pathogens in preterm infants. Supported by grants from NIH/NCATS (TL1-TR-002386) and the Biocodex Microbiota Foundation" @default.
- W4313404875 created "2023-01-06" @default.
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- W4313404875 date "2022-05-01" @default.
- W4313404875 modified "2023-09-27" @default.
- W4313404875 title "The preterm infant microbiome impairs lung immune responses to respiratory syncytial virus infection" @default.
- W4313404875 doi "https://doi.org/10.4049/jimmunol.208.supp.59.03" @default.
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