Antibiotics Potentiate Adherent-Invasive E. coli Infection and Expansion
Antibiotics Potentiate Adherent-Invasive E. coli Infection and Expansion
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DOI：
10.1093/ibd/izy361
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发表时间：
2019-04-01
影响因子：
4.9
通讯作者：
Coombes, Brian K.
中科院分区：
文献类型：
--
作者：
Oberc, Alexander M.;Fiebig-Comyn, Aline A.;Coombes, Brian K.
背景：克罗恩病（CD）是一种病因复杂的炎症性肠病。矛盾的是，乳糜泻与抗生素的使用和一种被称为粘附-侵袭性大肠杆菌（AIEC）的不寻常表型大肠杆菌群的丰度增加有关。然而，抗生素对AIEC感染的影响尚未在感染控制模型中得到很好的研究。方法：用多种不同种类的抗生素治疗前后感染AIEC小鼠。我们评估了AIEC在粪便和组织中的水平，AIEC在免疫荧光显微镜下的定位和组织病理学。结果：我们发现，在慢性感染小鼠中，广泛的抗生素类别强烈增强了初始AIEC感染并扩大了AIEC。我们发现抗生素增强AIEC感染的能力与肠道细菌群落的刻板转变无关，但与总体多样性的减少和抗生素前状态的分化有关。我们发现抗生素诱导的炎症通过在抗生素后时期使用氧化代谢物为AIEC扩张提供了适应性优势。结论：我们的研究结果表明，抗生素可以使宿主更容易感染初始AIEC，并且可以加重先前定殖宿主的感染。AIEC似乎利用宿主在抗生素后时期产生的炎症反应，强调了以前未知的CD危险因素之间的相互作用。
Background: Crohn's disease (CD) is an inflammatory bowel disease with a complex etiology. Paradoxically, CD is associated with the use of antibiotics and with an increased abundance of an unusual phenotypic group of Escherichia coli known as adherent-invasive E. coli (AIEC). However, the impact of antibiotics on AIEC infection has not been well studied in controlled models of infection.Methods: We infected mice with AIEC before or after treatment with a variety of different classes of antibiotics. We assessed levels of AIEC in the feces and tissues, AIEC localization by immunofluorescence microscopy, and tissue pathology.Results: We found that a wide range of antibiotic classes strongly potentiated initial AIEC infection and expanded AIEC in chronically infected mice. We found that the ability of antibiotics to potentiate AIEC infection did not correlate with a stereotyped shift in the gut bacterial community but was correlated with a decrease in overall diversity and a divergence from the pre-antibiotic state. We found that antibiotic-induced inflammation provided a fitness advantage for AIEC expansion through their use of oxidized metabolites in the postantibiotic period.Conclusions: Our results show that antibiotics can render hosts more susceptible to initial AIEC infection and can worsen infection in previously colonized hosts. AIEC appears to exploit host inflammatory responses that arise in the postantibiotic period, highlighting a previously unknown interaction between CD risk factors.