Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma

High-throughput sequencing (HTS) analysis of microbial communities from the respiratory airways has heavily relied on the 16S rRNA gene. Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its vari...

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Veröffentlicht in:PloS one 2015-06, Vol.10 (6), p.e0131819
Hauptverfasser: Pérez-Losada, Marcos, Castro-Nallar, Eduardo, Bendall, Matthew L, Freishtat, Robert J, Crandall, Keith A
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creator Pérez-Losada, Marcos
Castro-Nallar, Eduardo
Bendall, Matthew L
Freishtat, Robert J
Crandall, Keith A
description High-throughput sequencing (HTS) analysis of microbial communities from the respiratory airways has heavily relied on the 16S rRNA gene. Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. Consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota and even less to explore the microbe-host interactions. Here we present a simultaneous assessment of microbiome and host functional diversity and host-microbe interactions from the same RNA-seq experiment, while accounting for variation in clinical metadata. Transcriptomic (host) and metatranscriptomic (microbiota) sequences from the nasal epithelium of 8 asthmatics and 6 healthy controls were separated in silico and mapped to available human and NCBI-NR protein reference databases. Human genes differentially expressed in asthmatics and controls were then used to infer upstream regulators involved in immune and inflammatory responses. Concomitantly, microbial genes were mapped to metabolic databases (COG, SEED, and KEGG) to infer microbial functions differentially expressed in asthmatics and controls. Finally, multivariate analysis was applied to find associations between microbiome characteristics and host upstream regulators while accounting for clinical variation. Our study showed significant differences in the metabolism of microbiomes from asthmatic and non-asthmatic children for up to 25% of the functional properties tested. Enrichment analysis of 499 differentially expressed host genes for inflammatory and immune responses revealed 43 upstream regulators differentially activated in asthma. Microbial adhesion (virulence) and Proteobacteria abundance were significantly associated with variation in the expression of the upstream regulator IL1A; suggesting that microbiome characteristics modulate host inflammatory and immune systems during asthma.
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purification</subject><subject>Multivariate analysis</subject><subject>Nasal Mucosa - microbiology</subject><subject>Next-generation sequencing</subject><subject>NR protein</subject><subject>Pathogenesis</subject><subject>Pediatrics</subject><subject>Principal Component Analysis</subject><subject>Regulators</subject><subject>Respiratory diseases</subject><subject>Respiratory tract</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Ribosomal, 16S - genetics</subject><subject>rRNA 16S</subject><subject>Sequence Analysis, DNA</subject><subject>Studies</subject><subject>Taxonomy</subject><subject>Variation</subject><subject>Virulence</subject><subject>Virulence (Microbiology)</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2LEzEUhgdR3A_9B6IDguBFaz5mMpmbhbKrtrCyi67ehpOPaVOmk5pkZP33pu3s0gEFyUVCznPeJG_eLHuF0RTTCn9Yu9530E63rjNThCnmuH6SneKakgkjiD49Wp9kZyGsESopZ-x5dkIYJiWj5DSTVz20-Z2HLihvt9FtrMpvvWtsa7tl7pp87kLModP5F6u8k9ZFyHXvd9W5gTau9sUrGwwEk9suvzXaQvRJZxbiagMvsmcNtMG8HObz7Punj3eX88n1zefF5ex6olhN4qTkUJmikpzTujBEVhJL1ICuK4qgLiTTBBea1MzoimgDhVKKVUWJQWotKafn2ZuD7rZ1QQz2BIGTOuFVRetELA6EdrAWW2834H8LB1bsN5xfCvDRqtaIZGbFscSU8KZoGJW4lqWkBslSc0YhaV0Mp_VyY7QyXfTQjkTHlc6uxNL9EkWxe2GZBN4OAt797E2I_7jyQC0h3cp2jUtiamODErOCIIR4jXda079QaWiT_jMFJH2nGTe8HzUkJpr7uIQ-BLH49vX_2ZsfY_bdEbva5yO4to_WdWEMFgcwZSoEb5pH5zASu3w_uCF2-RZDvlPb62PXH5seAk3_ACU29UY</recordid><startdate>20150630</startdate><enddate>20150630</enddate><creator>Pérez-Losada, Marcos</creator><creator>Castro-Nallar, Eduardo</creator><creator>Bendall, Matthew L</creator><creator>Freishtat, Robert J</creator><creator>Crandall, Keith A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150630</creationdate><title>Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma</title><author>Pérez-Losada, Marcos ; 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Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. Consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota and even less to explore the microbe-host interactions. Here we present a simultaneous assessment of microbiome and host functional diversity and host-microbe interactions from the same RNA-seq experiment, while accounting for variation in clinical metadata. Transcriptomic (host) and metatranscriptomic (microbiota) sequences from the nasal epithelium of 8 asthmatics and 6 healthy controls were separated in silico and mapped to available human and NCBI-NR protein reference databases. Human genes differentially expressed in asthmatics and controls were then used to infer upstream regulators involved in immune and inflammatory responses. Concomitantly, microbial genes were mapped to metabolic databases (COG, SEED, and KEGG) to infer microbial functions differentially expressed in asthmatics and controls. Finally, multivariate analysis was applied to find associations between microbiome characteristics and host upstream regulators while accounting for clinical variation. Our study showed significant differences in the metabolism of microbiomes from asthmatic and non-asthmatic children for up to 25% of the functional properties tested. Enrichment analysis of 499 differentially expressed host genes for inflammatory and immune responses revealed 43 upstream regulators differentially activated in asthma. Microbial adhesion (virulence) and Proteobacteria abundance were significantly associated with variation in the expression of the upstream regulator IL1A; suggesting that microbiome characteristics modulate host inflammatory and immune systems during asthma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26125632</pmid><doi>10.1371/journal.pone.0131819</doi><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Analysis
Antibiotics
Asthma
Asthma - genetics
Asthma - immunology
Asthma - microbiology
Bacterial Adhesion - immunology
Base Sequence
Biodiversity
Biology
Child
Childhood asthma
Children
Children & youth
Consent
Data bases
Emergency medical care
Environmental factors
Epithelium
Female
Gene expression
Gene Expression Profiling
Genes
Genomes
Genomics
High-Throughput Nucleotide Sequencing
Host-Pathogen Interactions
Humans
Illnesses
Immune response
Immune system
Immunology
Inflammation
Inflammatory bowel disease
Interleukin 1
Interleukin-1alpha - biosynthesis
Male
Medicine
Metabolism
Microbial activity
Microbiomes
Microbiota
Microbiota (Symbiotic organisms)
Microbiota - genetics
Microorganisms
Moraxella catarrhalis
Moraxella catarrhalis - genetics
Moraxella catarrhalis - isolation & purification
Multivariate analysis
Nasal Mucosa - microbiology
Next-generation sequencing
NR protein
Pathogenesis
Pediatrics
Principal Component Analysis
Regulators
Respiratory diseases
Respiratory tract
Ribonucleic acid
RNA
RNA, Ribosomal, 16S - genetics
rRNA 16S
Sequence Analysis, DNA
Studies
Taxonomy
Variation
Virulence
Virulence (Microbiology)
Young Adult
title Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma
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