Maternal Antibiotic Treatment Dysregulates Goblet Cell Associated Antigen Passages in Neonatal Mice

Abstract

Abstract Maternal antibiotic treatment (MAT) disrupts the development of the neonatal microbiome, intestinal immune development and increases susceptibility to sepsis in mouse models. Mechanisms by which MAT disrupts neonatal intestinal immune function will facilitate the development of novel strategies to reduce neonatal sepsis risk. Intestinal goblet cell associated antigen passages (GAPs) are portals for physiologic exposure of the immune system to commensal gut bacteria and luminal antigens. GAPs are inhibited by epidermal growth factor receptor (EGFR) signaling, colonic GAPs are closed prior to postnatal day (P) 10 in mice when luminal EGF levels from breast milk are high, then open after P10 when breast milk EGF levels decline. When colonic GAPs are opened inappropriately due to low levels of EGF prior to P10 or dysbiosis of the gut microbiota after weaning, they can facilitate pathological bacterial translocation. Pups of dams treated with ampicillin and neomycin in their drinking water from pup P1–8 had significantly more open GAPs in the small intestine (SI) compared to controls. These data suggest that MAT creates a permissive environment for SI GAPs in the neonatal period which could allow pathologic bacterial translocation. MAT pups weighed significantly less and were significantly hypoglycemic compared to pups from control dams, after weaning MAT pups recover to a normal weight. We hypothesize that MAT pups have reduced intestinal EGFR signaling, leading to stunted growth and irregular opening of GAPs in the SI and colon. These data suggest maternal antibiotic treatment may be a risk factor for sepsis and growth failure in premature neonates.