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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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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0131819</identifier><identifier>PMID: 26125632</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2015-06, Vol.10 (6), p.e0131819</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Pérez-Losada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Pérez-Losada et al 2015 Pérez-Losada et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-58a7e47b88394e2b7b1b0fad9730a94b6d214d296ed72dea4ccc67451abddb383</citedby><cites>FETCH-LOGICAL-c692t-58a7e47b88394e2b7b1b0fad9730a94b6d214d296ed72dea4ccc67451abddb383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488395/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488395/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26125632$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Wilson, Brenda A</contributor><creatorcontrib>Pérez-Losada, Marcos</creatorcontrib><creatorcontrib>Castro-Nallar, Eduardo</creatorcontrib><creatorcontrib>Bendall, Matthew L</creatorcontrib><creatorcontrib>Freishtat, Robert J</creatorcontrib><creatorcontrib>Crandall, Keith A</creatorcontrib><title>Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Analysis</subject><subject>Antibiotics</subject><subject>Asthma</subject><subject>Asthma - genetics</subject><subject>Asthma - immunology</subject><subject>Asthma - microbiology</subject><subject>Bacterial Adhesion - immunology</subject><subject>Base Sequence</subject><subject>Biodiversity</subject><subject>Biology</subject><subject>Child</subject><subject>Childhood asthma</subject><subject>Children</subject><subject>Children & youth</subject><subject>Consent</subject><subject>Data bases</subject><subject>Emergency medical care</subject><subject>Environmental factors</subject><subject>Epithelium</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genomics</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Illnesses</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Interleukin 1</subject><subject>Interleukin-1alpha - biosynthesis</subject><subject>Male</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Microbial activity</subject><subject>Microbiomes</subject><subject>Microbiota</subject><subject>Microbiota (Symbiotic organisms)</subject><subject>Microbiota - genetics</subject><subject>Microorganisms</subject><subject>Moraxella catarrhalis</subject><subject>Moraxella catarrhalis - genetics</subject><subject>Moraxella catarrhalis - isolation & 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 ; Castro-Nallar, Eduardo ; Bendall, Matthew L ; Freishtat, Robert J ; Crandall, Keith A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-58a7e47b88394e2b7b1b0fad9730a94b6d214d296ed72dea4ccc67451abddb383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Analysis</topic><topic>Antibiotics</topic><topic>Asthma</topic><topic>Asthma - genetics</topic><topic>Asthma - immunology</topic><topic>Asthma - microbiology</topic><topic>Bacterial Adhesion - immunology</topic><topic>Base Sequence</topic><topic>Biodiversity</topic><topic>Biology</topic><topic>Child</topic><topic>Childhood asthma</topic><topic>Children</topic><topic>Children & youth</topic><topic>Consent</topic><topic>Data bases</topic><topic>Emergency medical care</topic><topic>Environmental factors</topic><topic>Epithelium</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Genes</topic><topic>Genomes</topic><topic>Genomics</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Host-Pathogen Interactions</topic><topic>Humans</topic><topic>Illnesses</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Inflammatory bowel disease</topic><topic>Interleukin 1</topic><topic>Interleukin-1alpha - biosynthesis</topic><topic>Male</topic><topic>Medicine</topic><topic>Metabolism</topic><topic>Microbial activity</topic><topic>Microbiomes</topic><topic>Microbiota</topic><topic>Microbiota (Symbiotic organisms)</topic><topic>Microbiota - 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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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recordid | cdi_plos_journals_1692287739 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
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 |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T02%3A08%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Dual%20Transcriptomic%20Profiling%20of%20Host%20and%20Microbiota%20during%20Health%20and%20Disease%20in%20Pediatric%20Asthma&rft.jtitle=PloS%20one&rft.au=P%C3%A9rez-Losada,%20Marcos&rft.date=2015-06-30&rft.volume=10&rft.issue=6&rft.spage=e0131819&rft.pages=e0131819-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0131819&rft_dat=%3Cgale_plos_%3EA420008915%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1692287739&rft_id=info:pmid/26125632&rft_galeid=A420008915&rft_doaj_id=oai_doaj_org_article_819781b1328f4f63b19b5b3e0b5d863a&rfr_iscdi=true |