PRENATAL ANTIBIOTIC THERAPY PREDISPOSES TO NEONATAL SEPSIS INDUCED BY E.COLI: A ROLE FOR BREAST MILK IGA?
Tesi di Dottorato
Data di Pubblicazione:
2021
Citazione:
PRENATAL ANTIBIOTIC THERAPY PREDISPOSES TO NEONATAL SEPSIS INDUCED BY E.COLI: A ROLE FOR BREAST MILK IGA? / C. Pietrasanta ; tutor: F. Mosca; co-tutor: M. Rescigno ; the chair of the doctoral program: L. Pinotti. Dipartimento di Scienze Cliniche e di Comunità, 2021 Dec 16. 34. ciclo, Anno Accademico 2021.
Abstract:
Antibiotics are administered to 20-30% of pregnant women, to treat maternal
infections or to prevent fetal and neonatal bacterial colonization in selected
cases of high infection risk, such as premature rupture of membranes (PROM).
Despite the administration of antibiotics to neonates, i.e. in the first days of
life, is known to increase the risk for subsequent late-onset sepsis (LOS),
necrotizing enterocolitis (NEC), and possibly of long term adverse outcomes
such as obesity and allergic manifestations, the effect of prenatal antibiotics
on neonatal immune development and function is poorly understood. Here,
using a murine model of prenatally-restricted antibiotic therapy (Abx), we
show that newborn mice born to mothers previously treated with Abx are
more susceptible to LOS caused by Escherichia coli, in correlation with an
increased bacterial translocation to distant organs (mesenteric lymph nodes,
spleen, liver). Increased neonatal mortality after maternal Abx did not
correlate with major modifications in blood or spleen populations of immune
cells (neutrophils, activated monocytes, CD4+ and CD8+ T cells), nor with
changes in gut epithelial structure and integrity, but correlated with a
significantly lower amount of fecal IgA, stomach IgA, IgA-coating of
intestinal bacteria, and IgA production by plasma cells of the maternal
mammary gland. Cross fostering experiments reinforced the evidence that
low breast milk IgA after maternal Abx was a key factor to increase the
mortality rate of pups. Moreover, the adverse effect of prenatal Abx persisted
after the interruption of breastfeeding, in weaned young adults. At 28 days of
life, prenatal Abx caused a reduction in IgA+ plasma cells, both CD11b+ and
CD11b-, in the lamina propria (LP) of the ileum, a reduction in faecal sIgA,
and decreased the amount of colonic T-regs and of Th17-like lymphocytes
(CD4+ RORgt+ antigen-specific T cells). Maternal supplementation with
postbiotics during the last 5 days of pregnancy was not sufficient to revert the
antibiotic-induced phenotype, at least in our experimental setting. Our data
highlight the importance of breast milk IgA for the prevention of neonatal
LOS, and the influence of prenatal Abx. If confirmed on human samples,
these results may lay the foundation for screening strategies of IgA in breast
milk, especially in selected high-risk situations such as prenatal Abx
administration, and/or extremely preterm neonates receiving maternal (or
donor) breast milk.
Tipologia IRIS:
Tesi di dottorato
Elenco autori:
C. Pietrasanta
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