The early colonization of the neonatal mouse gut by microbes is associated with protection from systemic bacterial infection later in life, according to a study published this week in Nature Medicine. These findings suggest that exposure to antibiotics near the time of birth can alter immune cell development and impair host defense to infections.
Commensal microbes in the gut provide signals that promote immune cell development. Previous studies have found that prolonged exposure of neonates to antibiotics perturbs colonization by microbes and is associated with increased risk of late-onset sepsis.
Hitesh Deshmukh, G Scott Worthen and colleagues found that prolonged exposure of neonatal mice to a clinically-relevant combination of three or five antibiotics in utero and after birth impaired their defense against sepsis caused by Escherichia coli (E. coli) K1 and Klebsiella pneumoniae infections. Shortly after birth, gut microbes normally induce the development and mobilization into the bloodstream of neutrophils, an immune cell type important for controlling E. coli infection. Perinatal antibiotic exposure reduces this early rise in neutrophil numbers. Transfer of microbes into antibiotic-treated mice increases neutrophil numbers in the circulation and bone marrow, restoring protection from sepsis caused by E. coli.
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