The effect of a single or multiple pulsed antibiotic exposure in C57BL/6 mice

Broad-spectrum antibiotics are frequently prescribed to children. The period of early-childhood represents a time where the developing microbiota may be more sensitive to environmental perturbations, which thus might have long-lasting host consequences. We hypothesized that even a single early-life broad-spectrum antibiotic course at a therapeutic dose (PAT) leads to durable alterations in both the gut microbiota and host immunity. In C57BL/6 mice, a single early-life tylosin (macrolide) course markedly altered the intestinal microbiome, and affected specific intestinal T-cell populations and secretory IgA expression, but PAT-exposed adult dams had minimal immunologic alterations. No immunological effects were detected in PAT-exposed germ-free animals; indicating that microbiota are required for the observed activities. Transfer of PAT-perturbed microbiota led to delayed sIgA expression indicating that the altered microbiota is sufficient to transfer PAT-induced effects. PAT exposure had lasting and transferable effects on microbial community network structure. Together these results indicate the impact of a single therapeutic early-life antibiotic course altering the microbiota and modulating host immune phenotypes that persist long after exposure has ceased. Nanostring gene expression analysis was performed on RNA extracted from the terminal ileum of control, PAT1 and PAT3 mice at week 7 of life.