临床上使用的广谱抗生素会损害肺部炎症性单细胞依赖的抗菌防御
Patrick J Dörner1, Harithaa Anandakumar2,3,4,5, Ivo Röwekamp1
1Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
在医院使用抗生素会破坏肠道细菌,削弱肺部对肺炎等感染的防御能力. 这种炎症单细胞的损伤损害了身体对抗多药耐药细菌的能力.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 医院获得的肺炎 (HAP) 具有显著的死亡率和经济负担,通常是由多药耐药 (MDR) 细菌驱动的.
- 之前的抗微生物治疗是已知的HAP风险因素,但确切的机制尚不清楚.
研究的目的:
- 研究抗生素治疗如何影响肠道微生物群和随后的肺部防御机制对抗MDR病原体.
- 阐明炎症单细胞 (IMs) 和它们在抗生素相关HAP中的信号通路的作用.
主要方法:
- 对接受抗生素治疗的住院患者的肠道微生物群多样性和短链脂肪酸 (SCFA) 生产群的分析.
- 使用从抗生素治疗患者的便微生物群移植来评估对MDR Klebsiella pneumoniae肺部防御的老鼠感染模型.
主要成果:
- 抗生素治疗导致肠道微生物群多样性减少和SCFA生产者的枯竭.
- 在小鼠中,抗生素诱导的微生物群变化损害了对MDR K. pneumoniae的肺部防御.
- 通过脂肪酸受体 (FFAR) 2/3调节的炎症单细胞 (IMs) 的抗菌活性在与抗生素相关的微生物群的小鼠中受到损害.
结论:
- 临床相关的抗生素可以通过改变人类肠道微生物群来损害抗菌防御.
- 确定IM抗菌活性的严重损害是将抗生素使用与增加HAP风险联系在一起的机制.
- 这些发现支持合理使用抗生素,并建议在高风险人群中预防HAP的新型预防策略.
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