Dynamics of intestinal IgA expression after early-life antibiotic treatment. (MUC9P.738)

Abstract

Abstract Class IgA secretory antibodies (SigA) are an early line of antigen-specific immune defenses that are influenced by commensal microbial populations. Perinatal antibiotic exposures may affect the host microbiota and have long-term consequences on host immunity. We hypothesize that early-life pulsed antibiotic treatment (PAT) perturbs the intestinal microbiota leading to alterations in sIgA expression. To test this hypothesis, C57BL/6 mice were exposed to 5 therapeutic doses of the β-lactam, amoxicillin, or the macrolide, tylosin. Exposure to either the tylosin or amoxicillin delayed sIgA expression. sIgA expression recovered in β-lactam-exposed mice but was abrogated with macrolide exposure. Compared to age-matched controls, 1 or 3 tylosin pulses decreased sIgA levels by 40% and 75%, respectively. Alterations in sIgA production were associated with decreased bacterial richness (α-diversity), altered community structure (β-diversity), and changes in microbial compositional, including increased abundance of Enterobacteriaceae and Bacteroides uniformis. Whereas tylosin had multiple immunological effects on conventional mice, essentially none were detected in germ-free animals; indicating that an antibiotic-perturbed microbiota influences developing immunity. These results provide evidence that early-life alterations of the intestinal microbiota by PAT modulates sIgA production, phenotypes that may persist after microbial recovery, with long-term consequences to host immunity.