title: Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients.
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.
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, The Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Wouter A A
authors.initials: WA
authors.lastname: de Steenhuijsen Piters
authors.affiliation: Laboratory of Medical Microbiology and Immunology, St Elisabeth Hospital, Tilburg, The Netherlands.|Department of Medical Microbiology, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
authors.forename: Elisabeth G W
authors.initials: EG
authors.lastname: Huijskens
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, The Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Wyllie
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, The Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Giske
authors.initials: G
authors.lastname: Biesbroek
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, The Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.|Linnaeus Institute, Spaarne Hospital, Hoofddorp, The Netherlands.
authors.forename: Menno R
authors.initials: MR
authors.lastname: van den Bergh
authors.affiliation: Linnaeus Institute, Spaarne Hospital, Hoofddorp, The Netherlands.
authors.forename: Reinier H
authors.initials: RH
authors.lastname: Veenhoven
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, The Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, The Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Trzciński
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Bonten
authors.affiliation: Laboratory of Medical Microbiology and Immunology, St Elisabeth Hospital, Tilburg, The Netherlands.|Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: John W A
authors.initials: JW
authors.lastname: Rossen
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, The Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
authors.affiliation: Department of Paediatric Immunology and Infectious Diseases, The Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Debby
authors.initials: D
authors.lastname: Bogaert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification*; D001424:Bacterial Infections / Q000382:microbiology*; D016022:Case-Control Studies; D064806:Dysbiosis / Q000382:microbiology*; D005260:Female; D006801:Humans; D008297:Male; D064307:Microbiota; D009960:Oropharynx / Q000382:microbiology*; D011014:Pneumonia / Q000382:microbiology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D012336:RNA, Ribosomal, 16S