Neonatal Susceptibility to Meningitis Results from the Immaturity of Epithelial Barriers and Gut Microbiota

Neonates are highly susceptible to bacterial meningitis as compared to children and adults. Group B streptococcus (GBS) is a major cause of neonatal meningitis. Neonatal meningitis can result from GBS intestinal colonization and translocation across the intestinal barrier (IB). Here, we show that the immaturity of the neonatal intestinal microbiota results in low resistance to GBS intestinal colonization and higher permissiveness of the gut vascular barrier. Additionally, the age-dependent but microbiota-independent Wnt activity in intestinal and choroid plexus (CP) epithelia results in a lower degree of cell-cell junctions’ polarization which favors bacterial translocation. This study reveals that neonatal susceptibility to GBS meningitis results from the age-dependent immaturity of the microbiota and developmental pathways associated with neonatal tissue growth, which concur to GBS gut colonization, systemic dissemination and neuroinvasion. Whereas the activation of developmental pathways is intrinsic to neonates, interventions aimed at maturing the microbiota may help prevent neonatal meningitis.