Integrating microbial and host transcriptomics to characterize asthma-associated microbial communities

Study information

Reviewed Marked as Reviewed by Folakunmi on 2023-12-18

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

26277095

DOI Digital object identifier for electronic documents.

10.1186/s12920-015-0121-1

URI

Authors

Castro-Nallar E, Shen Y, Freishtat RJ, Pérez-Losada M, Manimaran S, Liu G, Johnson WE, Crandall KA

Journal

BMC medical genomics

Year

2015

BACKGROUND: The relationships between infections in early life and asthma are not completely understood. Likewise, the clinical relevance of microbial communities present in the respiratory tract is only partially known. A number of microbiome studies analyzing respiratory tract samples have found increased proportions of gamma-Proteobacteria including Haemophilus influenzae, Moraxella catarrhalis, and Firmicutes such as Streptococcus pneumoniae. The aim of this study was to present a new approach that combines RNA microbial identification with host gene expression to characterize and validate metagenomic taxonomic profiling in individuals with asthma. METHODS: Using whole metagenomic shotgun RNA sequencing, we characterized and compared the microbial communities of individuals, children and adolescents, with asthma and controls. The resulting data were analyzed by partitioning human and microbial reads. Microbial reads were then used to characterize the microbial diversity of each patient, and potential differences between asthmatic and healthy groups. Human reads were used to assess the expression of known genes involved in the host immune response to specific pathogens and detect potential differences between those with asthma and controls. RESULTS: Microbial communities in the nasal cavities of children differed significantly between asthmatics and controls. After read count normalization, some bacterial species were significantly overrepresented in asthma patients (Wald test, p-value < 0.05), including Escherichia coli and Psychrobacter. Among these, Moraxella catarrhalis exhibited ~14-fold over abundance in asthmatics versus controls. Differential host gene expression analysis confirms that the presence of Moraxella catarrhalis is associated to a specific M. catarrhalis core gene signature expressed by the host. CONCLUSIONS: For the first time, we show the power of combining RNA taxonomic profiling and host gene expression signatures for microbial identification. Our approach not only identifies microbes from metagenomic data, but also adds support to these inferences by determining if the host is mounting a response against specific infectious agents. In particular, we show that M. catarrhalis is abundant in asthma patients but not in controls, and that its presence is associated with a specific host gene expression signature.

Experiment 1

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Reviewed Marked as Reviewed by Folakunmi on 2023-12-18

Curated date: 2023/10/30

Curator: MyleeeA

Revision editor(s): MyleeeA, Folakunmi

Subjects

Location of subjects: United States of America

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: Nasal cavity Cavitas nasalis,Cavitas nasi,Cavity of nose,Cavity of olfactory apparatus,Cavum nasi,Nasal canal,Nasal conduit space,Nasal fossa,Nasal pit,Olfactory cavity,Olfactory chamber,Olfactory chamber cavity,Olfactory pit,Nasal cavity,nasal cavity

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Asthma Airway hyperreactivity,asthma,Asthma (disorder),Asthma NOS,Asthma NOS (disorder),ASTHMA NOS W (AC) EXAC,Asthma unspecified,Asthma unspecified (disorder),Asthma, Bronchial,Asthma, unspecified,Asthma, unspecified type, with acute exacerbation,Asthma, unspecified type, without mention of status asthmaticus,Asthmas,Asthmatic,BHR - Bronchial hyperreactivity,Bronchial asthma,Bronchial Hyperreactivities,Bronchial hyperreactivity,bronchial hyperreactivity,Bronchial hyperresponsiveness,Bronchial hypersensitivity,chronic obstructive asthma,chronic obstructive asthma with acute exacerbation,chronic obstructive asthma with status asthmaticus,DUST PNEUMONOPATHY NEC,Exercise induced asthma,exercise induced asthma,Exercise-induced asthma,exercise-induced asthma,Exercise-induced asthma (disorder),Hyperreactive airway disease,Hyperreactive airways disease,Hyperreactivities, Bronchial,Hyperreactivity, Bronchial,Other forms of asthma,Pneumonopathy due to inhalation of other dust,Pneumopathy due to inhalation of other dust,Pneumopathy due to inhalation of other dust (disorder),Pneumopathy due to inhalation of other dust NOS,Pneumopathy due to inhalation of other dust NOS (disorder),Asthma

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

Group 1 name Corresponds to the case (exposed) group for case-control studies: Asthma Samples

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Participants ranged between the ages of 6 and 20 years, with physician-diagnosed asthma for at least one year prior to the time of recruitment.

Group 0 sample size Number of subjects in the control (unexposed) group: 6

Group 1 sample size Number of subjects in the case (exposed) group: 8

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

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

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

Statistical Analysis

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

Statistical test: DESeq2

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

Alpha Diversity

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

Chao1 Abundance-based estimator of species richness: increased

Simpson Estimator of species richness and species evenness: more weight on species evenness: decreased

Richness Number of species: increased

Signature 1

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Reviewed Marked as Reviewed by Folakunmi on 2023-12-18

Curated date: 2023/11/07

Curator: MyleeeA

Revision editor(s): MyleeeA, Folakunmi

Source: Figure 3b, and within result text (Microbial identification and relative abundance in asthma and control communities, paragraphs 2 and 3)

Description: Differential relative abundance between asthma and control communities

Abundance in Group 1: increased abundance in Asthma Samples

NCBI	Quality Control	Links
Escherichia coli
Moraxella catarrhalis
Psychrobacter sp. PRwf-1

Revision editor(s): MyleeeA, Folakunmi

Signature 2

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Reviewed Marked as Reviewed by Folakunmi on 2023-12-18

Curated date: 2023/11/07

Curator: MyleeeA

Revision editor(s): MyleeeA, Folakunmi

Source: Figure 3b, and within result text (Microbial identification and relative abundance in asthma and control communities, paragraphs 2 and 3)

Description: Differential relative abundance between asthma and control communities

Abundance in Group 1: decreased abundance in Asthma Samples

NCBI	Quality Control	Links
Anaerococcus prevotii

Revision editor(s): MyleeeA, Folakunmi