Understanding the effect of early-life pulsed antibiotic treatment on mucosal T-lymphocyte populations (MUC4P.827)

Abstract

Abstract Broad-spectrum antibiotics are frequently prescribed for children. The gut microbiota have functional roles in the development and differentiation of the host immune system. Early-life antibiotic use may have dynamic effects on the host microbiota, promoting long-term immunologic dysregulation and subsequent allergic and autoimmune pathology. Using a model of early-life antibiotic use, we hypothesize that early-life pulsed antibiotic treatment (PAT) -induced perturbation of the intestinal microbiota leads to alterations in tissue-specific and systemic T-cell populations. To test this hypothesis, we characterized splenic and ileal T-cell populations in control and PAT-treated C57BL/6 mice. Flow cytometric analysis demonstrated that early-life PAT significantly (p<0.05) decreased the frequency of splenic CD4+ and CD8+ T-cells and ileal CD4+ IL-17A+ Th17 populations. In contrast, ileal CD4+ Tbet+ (Th1) T cells and CD4+ Foxp3+ regulatory T-cell populations were significantly increased in PAT-treated mice. Alterations in immune cell populations were associated with microbial compositional changes, including significantly higher relative abundance of Enterobacteriaceae and Akkermansia muciniphila in PAT-treated mice. These results provide evidence that early-life perturbation of the intestinal microbiota by PAT modulates systemic and mucosal T-cell populations, phenotypes that may persist after microbial recovery, promoting life-long consequences to host immunity.