Abstract

BackgroundThe gut microbiome plays a protective role in the host defense against pneumonia. The composition of the lung microbiota has been shown to be predictive of clinical outcome in critically ill patients. However, the dynamics of the lung and gut microbiota composition over time during severe pneumonia remains ill defined. We used a mouse model of pneumonia-derived sepsis caused by Klebsiella pneumoniae in order to follow the pathogen burden as well as the composition of the lung, tongue and fecal microbiota from local infection towards systemic spread.ResultsAlready at 6 h post-inoculation with K. pneumoniae, marked changes in the lung microbiota were seen. The alpha diversity of the lung microbiota did not change throughout the infection, whereas the beta diversity did. A shift between the prominent lung microbiota members of Streptococcus and Klebsiella was seen from 12 h onwards and was most pronounced at 18 h post-inoculation (PI) which was also reflected in the release of pro-inflammatory cytokines indicating severe pulmonary inflammation. Around 18 h PI, K. pneumoniae bacteremia was observed together with a systemic inflammatory response. The composition of the tongue microbiota was not affected during infection, even at 18–30 h PI when K. pneumoniae had become the dominant bacterium in the lung. Moreover, we observed differences in the gut microbiota during pulmonary infection. The gut microbiota contributed to the lung microbiota at 12 h PI, however, this decreased at a later stage of the infection.ConclusionsAt 18 h PI, K. pneumoniae was the dominant member in the lung microbiota. The lung microbiota profiles were significantly explained by the lung K. pneumoniae bacterial counts and Klebsiella and Streptococcus were correlating with the measured cytokine levels in the lung and/or blood. The oral microbiota in mice, however, was not influenced by the severity of murine pneumonia, whereas the gut microbiota was affected. This study is of significance for future studies investigating the role of the lung microbiota during pneumonia and sepsis.

Highlights

  • The gut microbiome plays a protective role in the host defense against pneumonia

  • Dynamics of local and systemic bacterial loads and inflammation during K. pneumoniae pneumonia To investigate the changes of the lung microbiota during infection, we used our wellestablished mouse model of Klebsiella pneumoniae-induced pneumonia [26, 29]

  • The first blood cultures became positive 12 h PI, reaching significant differences from t = 0 at 18 h PI (Fig. 1c). This was reflected in pro-inflammatory cytokine profiles with a strong increase of Tumor necrosis factor-alpha (TNF-α), Interferon γ (IFN-γ), Interleukin 6 (IL-6) and monocyte chemoattractant protein -1 (MCP-1) levels appearing first locally in the lung after which all mice demonstrated elevated levels of these cytokines in blood already 18 h PI, which emphasizes the systemic inflammatory response syndrome seen in this model (Fig. 1d, e, Additional file 1: Fig. 1)

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Summary

Introduction

The gut microbiome plays a protective role in the host defense against pneumonia. The composition of the lung microbiota has been shown to be predictive of clinical outcome in critically ill patients. We used a mouse model of pneumonia-derived sepsis caused by Klebsiella pneumoniae in order to follow the pathogen burden as well as the composition of the lung, tongue and fecal microbiota from local infection towards systemic spread. Dickson et al [19] showed that the lung microbiome at admission was predictive of clinical outcome in ICU patients. Changes in the composition of the lung microbiome have been associated with susceptibility to influenza virus infection, the development of acute respiratory distress syndrome (ARDS) as well as poor outcome in patients with ARDS [20, 21]

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