Perinatal Antibiotic Timing Impairs Maternal IgG Transfer via FcRn and Shapes the Neonatal Gut Microbiome in Mice

TL;DR

Perinatal antibiotic use in mice disrupts the transfer of maternal antibodies and changes the baby's gut bacteria, which could affect immunity and health.

Contribution

This study reveals how timing of maternal antibiotic exposure affects IgG transfer and gut microbiome development in offspring.

Findings

Antibiotic treatment reduced IgG levels in mothers and offspring and downregulated FcRn expression.

Gestational exposure decreased gut microbiota diversity, while lactational exposure altered its composition.

Combined gestational and lactational exposure increased potential harmful bacteria like Enterococcus.

Abstract

Perinatal antibiotic exposure poses a significant risk to maternal-offspring immune programming and infant gut microbiota development. This study investigated the time-specific effects of maternal cefoperazone sodium (CPZ) administration on IgG transfer and offspring gut microbiota in a murine model. Pregnant C57BL/6J mice were assigned to control (CON), gestational (G-CPZ), lactational (L-CPZ), and combined gestational/lactational (GL-CPZ) treatment groups. Results showed that all CPZ treatments significantly reduced IgG and its subtype levels in maternal serum, colostrum, and offspring serum (p < 0.05). Concurrently, mRNA expression of the neonatal Fc receptor (FcRn), critical for IgG transport, was downregulated in both maternal breast and offspring intestinal tissues (p < 0.05). Furthermore, 16S rRNA sequencing revealed that CPZ exposure altered offspring gut microbiota diversity and composition. Alpha diversity was reduced, particularly in the G-CPZ group, while beta diversity showed significant separation in L-CPZ and GL-CPZ groups (p < 0.05). Taxonomic shifts included decreased Bacteroidetes and Lactobacillus, and in the GL-CPZ group, a marked increase in Firmicutes and potential pathobionts like Enterococcus and Hungatella (p < 0.05). These findings demonstrate that perinatal antibiotic exposure, depending on its timing, impairs maternal-offspring IgG transfer via the FcRn pathway and induces distinct, persistent alterations in the offspring’s gut microbiota, which may have implications for neonatal immunity and long-term health.

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