Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome.
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.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Robert P
0000-0002-6875-4277
RP
Dickson
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Benjamin H
BH
Singer
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Michael W
MW
Newstead
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Nicole R
NR
Falkowski
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
John R
JR
Erb-Downward
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Theodore J
TJ
Standiford
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.
Gary B
GB
Huffnagle
D000328:Adult; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D001439:Bacteroides / Q000254:growth & development / Q000302:isolation & purification; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D008168:Lung / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D064307:Microbiota; D008875:Middle Aged; D012128:Respiratory Distress Syndrome / Q000382:microbiology*; D018805:Sepsis / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha
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