Pulmonary and intestinal microbiota dynamics during Gram-negative pneumonia-derived sepsis

Intensive Care Medicine Experimental

Floor Hugenholtz¹  Max C. Jacobs¹  Nora S. Wolff¹  W. Joost Wiersinga² 

[1] Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands;Center for Experimental and Molecular Medicine, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands;Department of Medicine, Division of Infectious Diseases, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands;

关键词: Pneumonia;    Sepsis;    Klebsiella pneumoniae;    Microbiome;    Lung microbiota;    Gut microbiota;    Tongue;    Mice;    Dynamics over time;   

DOI  :  10.1186/s40635-021-00398-4

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY