Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/23

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

26151645

DOI Digital object identifier for electronic documents.

10.1038/ismej.2015.99

URI

Authors

de Steenhuijsen Piters WA, Huijskens EG, Wyllie AL, Biesbroek G, van den Bergh MR, Veenhoven RH, Wang X, Trzciński K, Bonten MJ, Rossen JW, Sanders EA, Bogaert D

Journal

The ISME journal

Year

2016

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.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/23

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Rimsha, Claregrieve1, ChiomaBlessing, Victoria

Subjects

Location of subjects: Netherlands

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Mucosa of oropharynx Mucosa of oral part of pharynx,Mucosa of organ of oral part of pharynx,Mucosa of organ of oropharynx,Mucous membrane of oral part of pharynx,Mucous membrane of oropharynx,Oral part of pharynx mucosa,Oral part of pharynx mucosa of organ,Oral part of pharynx mucous membrane,Oral part of pharynx organ mucosa,Organ mucosa of oral part of pharynx,Organ mucosa of oropharynx,Oropharynx mucosa,Oropharynx mucosa of organ,Oropharynx mucous membrane,Oropharynx organ mucosa,Mucosa of oropharynx,mucosa of oropharynx

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Pneumonia acute pneumonia,chest infection due to pneumonia,pneumonia,Pneumonia (disorder),Pneumonia (disorder) [Ambiguous],Pneumonia due to other specified organism,Pneumonia due to other specified organisms,Pneumonia due to other specified organisms (disorder),Pneumonia NOS,Pneumonia NOS (disorder),pneumonia with infectious disease,Pneumonitis,Pneumonitis (disorder),Pneumonia

Group 0 name Corresponds to the control (unexposed) group for case-control studies: elderly controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: elderly pneumonia patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: patients >= 60 years of age with pneumonia

Group 0 sample size Number of subjects in the control (unexposed) group: 91

Group 1 sample size Number of subjects in the case (exposed) group: 100

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 3 months

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V5-V7

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: raw counts

Statistical test: T-Test

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, smoking behavior, comorbidity

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: increased

Richness Number of species: decreased

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/23

Curated date: 2021/01/10

Curator: Rimsha Azhar

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Source: Figure 2

Description: Differential microbial abundance between elderly controls and elderly pneumonia patients

Abundance in Group 1: increased abundance in elderly pneumonia patients

NCBI	Quality Control	Links
Lactobacillus
Rothia
Streptococcus pseudopneumoniae

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/23

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): Claregrieve1, Merit, WikiWorks

Source: Figure 2

Description: Differential microbial abundance between elderly controls and elderly pneumonia patients

Abundance in Group 1: decreased abundance in elderly pneumonia patients

NCBI	Quality Control	Links
Leptotrichia
Parascardovia
Prevotella melaninogenica
Veillonella dispar

Revision editor(s): Claregrieve1, Merit, WikiWorks

Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/23

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Rimsha, Claregrieve1, ChiomaBlessing, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: adult controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: adult pneumonia patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: patients <60 years of age with pneumonia