The role of the microbiome in exacerbations of chronic lung diseases.
The role of the microbiome in exacerbations of chronic lung diseases.
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DOI：
10.1016/s0140-6736(14)61136-3
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发表时间：
2014-08-23
期刊：
影响因子：
168.9
通讯作者：
Huffnagle, Gary B.
中科院分区：
文献类型：
--
作者：
Dickson, Robert P.;Martinez, Fernando J.;Huffnagle, Gary B.
非培养物依赖性微生物学技术揭示了呼吸道细菌微生物组的先前未被认识到的复杂性，迫使重新考虑宿主、细菌和慢性肺部疾病加重的发病机制之间的相互作用。肺部微生物组的组成由微生物的迁移、消除及其成员的相对生长速率决定;所有这些在慢性肺病中以及在急性加重期间都发生显著变化。急性加重缺乏细菌感染的关键特征，包括细菌负荷增加和群落多样性降低。相反，我们认为病情加重是呼吸道生态失调的情况：一种对宿主生物学产生负面影响的紊乱的呼吸道微生物生态系统。呼吸道生态失调引起失调的宿主免疫应答，这反过来改变患者气道中的微生物生长条件，进一步促进生态失调并使炎症和紊乱的微生物群的耦合循环永久化。基线呼吸道微生物群的差异可能有助于解释在多种疾病状态下观察到的"频繁加重"表型，并可能为治疗干预提供新的靶点。
Culture-independent microbiological techniques have revealed a previously unappreciated complexity to the bacterial microbiome of the respiratory tract, forcing reconsideration of the interactions between host, bacteria and the pathogenesis of exacerbations of chronic lung disease. The composition of the lung microbiome is determined by microbial immigration, elimination, and the relative growth rates of its members; all of these change dramatically in chronic lung disease and further during exacerbations. Exacerbations lack key features of bacterial infections, including increased bacterial burden and decreased community diversity. We propose instead that exacerbations are occasions of respiratory dysbiosis: a disordered respiratory microbial ecosystem with negative effects on host biology. Respiratory dysbiosis provokes a dysregulated host immune response, which in turn alters microbial growth conditions in patient airways, further promoting dysbiosis and perpetuating a coupled cycle of inflammation and disordered microbiota. Differences in baseline respiratory microbiota may help explain the “frequent-exacerbator” phenotype observed across multiple disease states, and may provide novel targets for therapeutic intervention.