Abstract
Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.
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Acknowledgements
This research has received funding from the Wilhelmina Children’s Hospital Fund, ZonMW (grant 91209010) and NWO-VENI (grant 91610121). We thank Mei Ling Chu for her technical assistance and Dr Marinus JC Eijkemans for his input on the statistical analysis. This work is dedicated to the memory of Dr Reinier H Veenhoven who contributed to the planning of the design and execution of the clinical studies in healthy controls and Dr Marcel F Peeters, who was investigator in the adult pneumonia study.
Author contributions
RHV, MJB, EAMS, JWAR and DB designed the study. EGWH, GB and MRvdB wrote the study protocols. EGWH, GB, MRvdB and RHV were responsible for the recruitment of patients and collection of the samples. KT, EGWH and ALW were responsible for the conventional culturing/qPCR on the samples. ALW was responsible for sample preparation for pyrosequencing. WAAdSP, DB and XW were responsible for the post-processing of sequences and data analysis. All authors were involved in data interpretation and drafting of the manuscript.
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EAMS declares to have received unrestricted research support from Pfizer, grant support for vaccine studies from Pfizer and GlaxoSmithKline and fees paid to the institution for advisory boards or participation in independent data monitoring committees for Pfizer and GSK. RHV reported receiving grant support from GlaxoSmithKline and Wyeth/Pfizer for vaccine studies and consulting fees from GlaxoSmithKline. KT received grant support and consulting fees from Pfizer. DB received consulting fees from Pfizer. These grants and fees were not received for the research described in this paper. The remaining authors declare no conflict of interest.
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de Steenhuijsen Piters, W., Huijskens, E., Wyllie, A. et al. Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients. ISME J 10, 97–108 (2016). https://doi.org/10.1038/ismej.2015.99
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DOI: https://doi.org/10.1038/ismej.2015.99
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