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

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.