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

Abstract

SUMMARY 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. Ecologic 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.

The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia

“…Therefore, we do not reject the hypothesis that antibiotics influence the pulmonary microbiome, although we can state that the influence is not as overwhelming as might be expected. This is also exemplified in a recent animal study, in which treatment of rats with imipenem led to little disturbance 38. Despite the small sample size, a statistically significant effect for duration of mechanical ventilation was found and several differences were identified between patients who did and did not develop pneumonia.…”

Gastrointestinal microbiota contributes to the development of murine transfusion-related acute lung injury

“…On the other hand, it was recently reported that the lung microbiota in both sepsis and acute respiratory distress syndrome (ARDS) is enriched for bacteria that are usually found in the lower GI tract. 36 Moreover, the abundance of gut bacteria in human ARDS samples correlated with disease severity, indicating the gut's microbiota plays a pathogenic role. 36 We found that in contrast to the BF mice, untreated SPF mice or BF mice treated with antibiotics (gut flora depleted) were protected from antibody-mediated TRALI (Figures 2 and 3).…”

“…36 Moreover, the abundance of gut bacteria in human ARDS samples correlated with disease severity, indicating the gut's microbiota plays a pathogenic role. 36 We found that in contrast to the BF mice, untreated SPF mice or BF mice treated with antibiotics (gut flora depleted) were protected from antibody-mediated TRALI (Figures 2 and 3). This pathogenic TRALI response was not mousevendor dependent, but was determined by the housing conditions ( Figure 2B).…”

The gut microbiota of critically ill patients: first steps in an unexplored world

“…Nonetheless, dysbiosis could impair gut barrier functions and worsen post-aggressive immunosuppression, thereby easing the occurrence of ICU-acquired sepsis and protracted multiorgan failure [4]. Also, experimental models suggest that the composition of the gut ecosystem might modulate the risk of complications such as acute respiratory distress syndrome [8], ischemia/reperfusion-related acute kidney injury [9], or sepsis-induced muscle wasting [10].…”