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单一早期大环内酯疗程对鼠类微生物网络拓扑和免疫有持久影响。

A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity.

机构信息

Departments of Medicine and Microbiology, New York University School of Medicine (NYUSM), New York, NY, 10016, USA.

Janssen R&D, Janssen Pharmaceutical Companies of J&J, Turnhoutseweg 30, Beerse, 2340, Belgium.

出版信息

Nat Commun. 2017 Sep 11;8(1):518. doi: 10.1038/s41467-017-00531-6.

Abstract

Broad-spectrum antibiotics are frequently prescribed to children. Early childhood represents a dynamic period for the intestinal microbial ecosystem, which is readily shaped by environmental cues; antibiotic-induced disruption of this sensitive community may have long-lasting host consequences. Here we demonstrate that a single pulsed macrolide antibiotic treatment (PAT) course early in life is sufficient to lead to durable alterations to the murine intestinal microbiota, ileal gene expression, specific intestinal T-cell populations, and secretory IgA expression. A PAT-perturbed microbial community is necessary for host effects and sufficient to transfer delayed secretory IgA expression. Additionally, early-life antibiotic exposure has lasting and transferable effects on microbial community network topology. Our results indicate that a single early-life macrolide course can alter the microbiota and modulate host immune phenotypes that persist long after exposure has ceased.High or multiple doses of macrolide antibiotics, when given early in life, can perturb the metabolic and immunological development of lab mice. Here, Ruiz et al. show that even a single macrolide course, given early in life, leads to long-lasting changes in the gut microbiota and immune system of mice.

摘要

广谱抗生素经常被开给儿童使用。婴幼儿期是肠道微生物生态系统活跃的时期,其很容易受到环境线索的影响;抗生素诱导的这种敏感群落的破坏可能会对宿主产生持久的后果。在这里,我们证明,生命早期单次脉冲大环内酯类抗生素治疗(PAT)疗程足以导致鼠类肠道微生物群、回肠基因表达、特定肠道 T 细胞群体和分泌型 IgA 表达的持久改变。受 PAT 干扰的微生物群落是宿主效应所必需的,并且足以转移延迟的分泌型 IgA 表达。此外,生命早期抗生素暴露对微生物群落网络拓扑结构具有持久和可传递的影响。我们的研究结果表明,单次生命早期大环内酯类疗程可改变微生物群,并调节宿主免疫表型,这些表型在暴露停止后仍持续存在。高剂量或多次给予大环内酯类抗生素,在生命早期使用时,会扰乱实验小鼠的代谢和免疫发育。在这里,Ruiz 等人表明,即使是生命早期单次大环内酯类疗程,也会导致小鼠肠道微生物群和免疫系统的持久变化。

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