Viable bacterial colonization is limited in the human intestine in utero

Abstract

Abstract Mucosal immunity develops in the human fetal intestine by 11–14 weeks gestation, yet whether viable microbes exist in utero and interact with intestinal immunity is unknown. Structures consistent with coccoid bacterial morphology, embedded in fetal meconium were evident before mid-gestation by high-resolution scanning electron microscopy (n=4). Molecular methods indicated extremely low bacterial burden and simple profiles in fetal meconium (n=40 of 50) compared to controls (n=87). A subset of Micrococcaceae-dominated (n=9) meconium associated with proportions of lamina propria PLZF+ CD161+ CD4+ T cells and divergent intestinal epithelial transcriptomes. Fetal Micrococcus luteus was isolated only in the presence of a monocyte feeder cell line. This strain grew on placental hormones, remained viable within fetal antigen presenting cells, exhibited species-specific immunomodulatory capacity and genomic features indicating fetal adaptation. Thus, viable bacteria are highly limited and inconsistently detectable in human fetal meconium at mid-gestation.