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脓毒症和急性呼吸窘迫综合征中肠道细菌对肺部微生物组的富集。

Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome.

机构信息

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

出版信息

Nat Microbiol. 2016 Jul 18;1(10):16113. doi: 10.1038/nmicrobiol.2016.113.

Abstract

Sepsis and the acute respiratory distress syndrome (ARDS) are major causes of mortality without targeted therapies. Although many experimental and clinical observations have implicated gut microbiota in the pathogenesis of these diseases, culture-based studies have failed to demonstrate translocation of bacteria to the lungs in critically ill patients. Here, we report culture-independent evidence that the lung microbiome is enriched with gut bacteria both in a murine model of sepsis and in humans with established ARDS. Following experimental sepsis, lung communities were dominated by viable gut-associated bacteria. Ecological analysis identified the lower gastrointestinal tract, rather than the upper respiratory tract, as the likely source community of post-sepsis lung bacteria. In bronchoalveolar lavage fluid from humans with ARDS, gut-specific bacteria (Bacteroides spp.) were common and abundant, undetected by culture and correlated with the intensity of systemic inflammation. Alveolar TNF-α, a key mediator of alveolar inflammation in ARDS, was significantly correlated with altered lung microbiota. Our results demonstrate that the lung microbiome is enriched with gut-associated bacteria in sepsis and ARDS, potentially representing a shared mechanism of pathogenesis in these common and lethal diseases.

摘要

脓毒症和急性呼吸窘迫综合征(ARDS)是目前缺乏靶向治疗方法的主要致死原因。虽然许多实验和临床观察表明肠道微生物群与这些疾病的发病机制有关,但基于培养的研究未能证明在危重病患者中细菌向肺部转移。在这里,我们报告了非培养依赖性证据,即在脓毒症的小鼠模型和已确诊的 ARDS 患者中,肺部微生物组富含肠道细菌。在实验性脓毒症后,肺部群落主要由具有活力的肠道相关细菌主导。生态分析确定了下消化道,而不是上呼吸道,是脓毒症后肺部细菌的可能来源群落。在 ARDS 患者的支气管肺泡灌洗液中,常见且丰富的是肠道特异性细菌(拟杆菌属),培养法无法检测到这些细菌,并且与全身炎症的强度相关。肺泡 TNF-α是 ARDS 中肺泡炎症的关键介质,与改变的肺部微生物组有显著相关性。我们的结果表明,在脓毒症和 ARDS 中,肺部微生物组富含与肠道相关的细菌,这可能代表这些常见且致命疾病的共同发病机制。

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