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Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children

Identifieur interne : 000223 ( Pmc/Checkpoint ); précédent : 000222; suivant : 000224

Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children

Auteurs : Leah Cuthbertson [Royaume-Uni] ; Stephen W. C. Oo [Australie] ; Michael J. Cox [Royaume-Uni] ; Siew-Kim Khoo [Australie] ; Des W. Cox [Australie] ; Glenys Chidlow [Australie] ; Kimberley Franks [Australie] ; Franciska Prastanti [Australie] ; Meredith L. Borland [Australie] ; James E. Gern [États-Unis] ; David W. Smith [Australie] ; Joelene A. Bizzintino [Australie] ; Ingrid A. Laing [Australie] ; Peter N. Le Souëf [Australie] ; Miriam F. Moffatt [Royaume-Uni] ; William O. C. Cookson [Royaume-Uni]

Source :

RBID : PMC:6797130

Abstract

Acute viral wheeze in children is a major cause of hospitalisation and a major risk factor for the development of asthma. However, the role of the respiratory tract microbiome in the development of acute wheeze is unclear. To investigate whether severe wheezing episodes in children are associated with bacterial dysbiosis in the respiratory tract, oropharyngeal swabs were collected from 109 children with acute wheezing attending the only tertiary paediatric hospital in Perth, Australia. The bacterial community from these samples was explored using next generation sequencing and compared to samples from 75 non-wheezing controls. No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Within the wheezing group, attendance at kindergarten or preschool was however, associated with increased bacterial diversity. Rhinovirus (RV) infection did not have a significant effect on bacterial community composition. A significant difference in bacterial richness was observed between children with RV-A and RV-C infection, however this is likely due to the differences in age group between the patient cohorts. The bacterial community within the oropharynx was found to be diverse and heterogeneous. Age and attendance at day care or kindergarten were important factors in driving bacterial diversity. However, wheeze and viral infection were not found to significantly relate to the bacterial community. Bacterial airway microbiome is highly variable in early life and its role in wheeze remains less clear than viral influences.


Url:
DOI: 10.1371/journal.pone.0223990
PubMed: 31622414
PubMed Central: 6797130


Affiliations:


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PMC:6797130

Le document en format XML

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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Division of Emergency Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Gern, James E" sort="Gern, James E" uniqKey="Gern J" first="James E." last="Gern">James E. Gern</name>
<affiliation wicri:level="2">
<nlm:aff id="aff008">
<addr-line>Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin</wicri:regionArea>
<placeName>
<region type="state">Wisconsin</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Smith, David W" sort="Smith, David W" uniqKey="Smith D" first="David W." last="Smith">David W. Smith</name>
<affiliation wicri:level="1">
<nlm:aff id="aff002">
<addr-line>Division of Paediatrics, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Division of Paediatrics, Faculty of Health and Medical Sciences, University of Western Australia, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff005">
<addr-line>Department of Microbiology, PathWest Laboratory Medicine WA, QEII Medical Centre, Perth, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology, PathWest Laboratory Medicine WA, QEII Medical Centre, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff009">
<addr-line>Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Bizzintino, Joelene A" sort="Bizzintino, Joelene A" uniqKey="Bizzintino J" first="Joelene A." last="Bizzintino">Joelene A. Bizzintino</name>
<affiliation wicri:level="1">
<nlm:aff id="aff002">
<addr-line>Division of Paediatrics, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Division of Paediatrics, Faculty of Health and Medical Sciences, University of Western Australia, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff004">
<addr-line>Telethon Kids Institute, Perth, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Telethon Kids Institute, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Laing, Ingrid A" sort="Laing, Ingrid A" uniqKey="Laing I" first="Ingrid A." last="Laing">Ingrid A. Laing</name>
<affiliation>
<nlm:aff>NONE</nlm:aff>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff004">
<addr-line>Telethon Kids Institute, Perth, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Telethon Kids Institute, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Le Souef, Peter N" sort="Le Souef, Peter N" uniqKey="Le Souef P" first="Peter N." last="Le Souëf">Peter N. Le Souëf</name>
<affiliation wicri:level="1">
<nlm:aff id="aff002">
<addr-line>Division of Paediatrics, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Division of Paediatrics, Faculty of Health and Medical Sciences, University of Western Australia, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff004">
<addr-line>Telethon Kids Institute, Perth, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Telethon Kids Institute, Perth</wicri:regionArea>
<wicri:noRegion>Perth</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Moffatt, Miriam F" sort="Moffatt, Miriam F" uniqKey="Moffatt M" first="Miriam F." last="Moffatt">Miriam F. Moffatt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>National Heart and Lung Institute, Imperial College, London, England, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>National Heart and Lung Institute, Imperial College, London, England</wicri:regionArea>
<wicri:noRegion>England</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cookson, William O C" sort="Cookson, William O C" uniqKey="Cookson W" first="William O. C." last="Cookson">William O. C. Cookson</name>
<affiliation wicri:level="1">
<nlm:aff id="aff001">
<addr-line>National Heart and Lung Institute, Imperial College, London, England, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>National Heart and Lung Institute, Imperial College, London, England</wicri:regionArea>
<wicri:noRegion>England</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff010">
<addr-line>Royal Brompton and Harefield NHS Foundation Trust, London, England, United Kingdom</addr-line>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Royal Brompton and Harefield NHS Foundation Trust, London, England</wicri:regionArea>
<wicri:noRegion>England</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint>
<date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Acute viral wheeze in children is a major cause of hospitalisation and a major risk factor for the development of asthma. However, the role of the respiratory tract microbiome in the development of acute wheeze is unclear. To investigate whether severe wheezing episodes in children are associated with bacterial dysbiosis in the respiratory tract, oropharyngeal swabs were collected from 109 children with acute wheezing attending the only tertiary paediatric hospital in Perth, Australia. The bacterial community from these samples was explored using next generation sequencing and compared to samples from 75 non-wheezing controls. No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Within the wheezing group, attendance at kindergarten or preschool was however, associated with increased bacterial diversity. Rhinovirus (RV) infection did not have a significant effect on bacterial community composition. A significant difference in bacterial richness was observed between children with RV-A and RV-C infection, however this is likely due to the differences in age group between the patient cohorts. The bacterial community within the oropharynx was found to be diverse and heterogeneous. Age and attendance at day care or kindergarten were important factors in driving bacterial diversity. However, wheeze and viral infection were not found to significantly relate to the bacterial community. Bacterial airway microbiome is highly variable in early life and its role in wheeze remains less clear than viral influences.</p>
</div>
</front>
<back>
<div1 type="bibliography">
<listBibl>
<biblStruct>
<analytic>
<author>
<name sortKey="Goto, T" uniqKey="Goto T">T Goto</name>
</author>
<author>
<name sortKey="Tsugawa, Y" uniqKey="Tsugawa Y">Y Tsugawa</name>
</author>
<author>
<name sortKey="Mansbach, Jm" uniqKey="Mansbach J">JM Mansbach</name>
</author>
<author>
<name sortKey="Camargo, Ca" uniqKey="Camargo C">CA Camargo</name>
</author>
<author>
<name sortKey="Hasegawa, K" uniqKey="Hasegawa K">K Hasegawa</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bisgaard, H" uniqKey="Bisgaard H">H Bisgaard</name>
</author>
<author>
<name sortKey="Hermansen, Mn" uniqKey="Hermansen M">MN Hermansen</name>
</author>
<author>
<name sortKey="Buchvald, F" uniqKey="Buchvald F">F Buchvald</name>
</author>
<author>
<name sortKey="Loland, L" uniqKey="Loland L">L Loland</name>
</author>
<author>
<name sortKey="Halkjaer, Lb" uniqKey="Halkjaer L">LB Halkjaer</name>
</author>
<author>
<name sortKey="Bonnelykke, K" uniqKey="Bonnelykke K">K Bonnelykke</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ege, Mj" uniqKey="Ege M">MJ Ege</name>
</author>
<author>
<name sortKey="Mayer, M" uniqKey="Mayer M">M Mayer</name>
</author>
<author>
<name sortKey="Normand, Ac" uniqKey="Normand A">AC Normand</name>
</author>
<author>
<name sortKey="Genuneit, J" uniqKey="Genuneit J">J Genuneit</name>
</author>
<author>
<name sortKey="Cookson, Wo" uniqKey="Cookson W">WO Cookson</name>
</author>
<author>
<name sortKey="Braun Fahrlander, C" uniqKey="Braun Fahrlander C">C Braun-Fahrlander</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Castro Rodriguez, Ja" uniqKey="Castro Rodriguez J">JA Castro-Rodriguez</name>
</author>
<author>
<name sortKey="Forno, E" uniqKey="Forno E">E Forno</name>
</author>
<author>
<name sortKey="Rodriguez Martinez, Ce" uniqKey="Rodriguez Martinez C">CE Rodriguez-Martinez</name>
</author>
<author>
<name sortKey="Celedon, Jc" uniqKey="Celedon J">JC Celedon</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Stern, Da" uniqKey="Stern D">DA Stern</name>
</author>
<author>
<name sortKey="Morgan, Wj" uniqKey="Morgan W">WJ Morgan</name>
</author>
<author>
<name sortKey="Halonen, M" uniqKey="Halonen M">M Halonen</name>
</author>
<author>
<name sortKey="Wright, Al" uniqKey="Wright A">AL Wright</name>
</author>
<author>
<name sortKey="Martinez, Fd" uniqKey="Martinez F">FD Martinez</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Mirzakhani, H" uniqKey="Mirzakhani H">H Mirzakhani</name>
</author>
<author>
<name sortKey="Carey, Vj" uniqKey="Carey V">VJ Carey</name>
</author>
<author>
<name sortKey="Zeiger, R" uniqKey="Zeiger R">R Zeiger</name>
</author>
<author>
<name sortKey="Bacharier, Lb" uniqKey="Bacharier L">LB Bacharier</name>
</author>
<author>
<name sortKey="O Connor, Gt" uniqKey="O Connor G">GT O'Connor</name>
</author>
<author>
<name sortKey="Schatz, Mx" uniqKey="Schatz M">MX Schatz</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bizzintino, J" uniqKey="Bizzintino J">J Bizzintino</name>
</author>
<author>
<name sortKey="Lee, Wm" uniqKey="Lee W">WM Lee</name>
</author>
<author>
<name sortKey="Laing, Ia" uniqKey="Laing I">IA Laing</name>
</author>
<author>
<name sortKey="Vang, F" uniqKey="Vang F">F Vang</name>
</author>
<author>
<name sortKey="Pappas, T" uniqKey="Pappas T">T Pappas</name>
</author>
<author>
<name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bacharier, Lb" uniqKey="Bacharier L">LB Bacharier</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Rossi, Ga" uniqKey="Rossi G">GA Rossi</name>
</author>
<author>
<name sortKey="Colin, Aa" uniqKey="Colin A">AA Colin</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Miller, Ek" uniqKey="Miller E">EK Miller</name>
</author>
<author>
<name sortKey="Bugna, J" uniqKey="Bugna J">J Bugna</name>
</author>
<author>
<name sortKey="Libster, R" uniqKey="Libster R">R Libster</name>
</author>
<author>
<name sortKey="Shepherd, Be" uniqKey="Shepherd B">BE Shepherd</name>
</author>
<author>
<name sortKey="Scalzo, Pm" uniqKey="Scalzo P">PM Scalzo</name>
</author>
<author>
<name sortKey="Acosta, Pl" uniqKey="Acosta P">PL Acosta</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Biesbroek, G" uniqKey="Biesbroek G">G Biesbroek</name>
</author>
<author>
<name sortKey="Tsivtsivadze, E" uniqKey="Tsivtsivadze E">E Tsivtsivadze</name>
</author>
<author>
<name sortKey="Sanders, Ea" uniqKey="Sanders E">EA Sanders</name>
</author>
<author>
<name sortKey="Montijn, R" uniqKey="Montijn R">R Montijn</name>
</author>
<author>
<name sortKey="Veenhoven, Rh" uniqKey="Veenhoven R">RH Veenhoven</name>
</author>
<author>
<name sortKey="Keijser, Bj" uniqKey="Keijser B">BJ Keijser</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bosch, A" uniqKey="Bosch A">A Bosch</name>
</author>
<author>
<name sortKey="De Steenhuijsen Piters, Waa" uniqKey="De Steenhuijsen Piters W">WAA de Steenhuijsen Piters</name>
</author>
<author>
<name sortKey="Van Houten, Ma" uniqKey="Van Houten M">MA van Houten</name>
</author>
<author>
<name sortKey="Chu, M" uniqKey="Chu M">M Chu</name>
</author>
<author>
<name sortKey="Biesbroek, G" uniqKey="Biesbroek G">G Biesbroek</name>
</author>
<author>
<name sortKey="Kool, J" uniqKey="Kool J">J Kool</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Folsgaard, Nv" uniqKey="Folsgaard N">NV Folsgaard</name>
</author>
<author>
<name sortKey="Schjorring, S" uniqKey="Schjorring S">S Schjorring</name>
</author>
<author>
<name sortKey="Chawes, Bl" uniqKey="Chawes B">BL Chawes</name>
</author>
<author>
<name sortKey="Rasmussen, Ma" uniqKey="Rasmussen M">MA Rasmussen</name>
</author>
<author>
<name sortKey="Krogfelt, Ka" uniqKey="Krogfelt K">KA Krogfelt</name>
</author>
<author>
<name sortKey="Brix, S" uniqKey="Brix S">S Brix</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lee, Wm" uniqKey="Lee W">WM Lee</name>
</author>
<author>
<name sortKey="Grindle, K" uniqKey="Grindle K">K Grindle</name>
</author>
<author>
<name sortKey="Pappas, T" uniqKey="Pappas T">T Pappas</name>
</author>
<author>
<name sortKey="Marshall, Dj" uniqKey="Marshall D">DJ Marshall</name>
</author>
<author>
<name sortKey="Moser, Mj" uniqKey="Moser M">MJ Moser</name>
</author>
<author>
<name sortKey="Beaty, El" uniqKey="Beaty E">EL Beaty</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bochkov, Ya" uniqKey="Bochkov Y">YA Bochkov</name>
</author>
<author>
<name sortKey="Grindle, K" uniqKey="Grindle K">K Grindle</name>
</author>
<author>
<name sortKey="Vang, F" uniqKey="Vang F">F Vang</name>
</author>
<author>
<name sortKey="Evans, Md" uniqKey="Evans M">MD Evans</name>
</author>
<author>
<name sortKey="Gern, Je" uniqKey="Gern J">JE Gern</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lee, Wm" uniqKey="Lee W">WM Lee</name>
</author>
<author>
<name sortKey="Kiesner, C" uniqKey="Kiesner C">C Kiesner</name>
</author>
<author>
<name sortKey="Pappas, T" uniqKey="Pappas T">T Pappas</name>
</author>
<author>
<name sortKey="Lee, I" uniqKey="Lee I">I Lee</name>
</author>
<author>
<name sortKey="Grindle, K" uniqKey="Grindle K">K Grindle</name>
</author>
<author>
<name sortKey="Jartti, T" uniqKey="Jartti T">T Jartti</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Chidlow, Gr" uniqKey="Chidlow G">GR Chidlow</name>
</author>
<author>
<name sortKey="Harnett, Gb" uniqKey="Harnett G">GB Harnett</name>
</author>
<author>
<name sortKey="Shellam, Gr" uniqKey="Shellam G">GR Shellam</name>
</author>
<author>
<name sortKey="Smith, Dw" uniqKey="Smith D">DW Smith</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Subrata, Ls" uniqKey="Subrata L">LS Subrata</name>
</author>
<author>
<name sortKey="Bizzintino, J" uniqKey="Bizzintino J">J Bizzintino</name>
</author>
<author>
<name sortKey="Mamessier, E" uniqKey="Mamessier E">E Mamessier</name>
</author>
<author>
<name sortKey="Bosco, A" uniqKey="Bosco A">A Bosco</name>
</author>
<author>
<name sortKey="Mckenna, Kl" uniqKey="Mckenna K">KL McKenna</name>
</author>
<author>
<name sortKey="Wikstrom, Me" uniqKey="Wikstrom M">ME Wikstrom</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Cuthbertson, L" uniqKey="Cuthbertson L">L Cuthbertson</name>
</author>
<author>
<name sortKey="Craven, V" uniqKey="Craven V">V Craven</name>
</author>
<author>
<name sortKey="Bingle, L" uniqKey="Bingle L">L Bingle</name>
</author>
<author>
<name sortKey="Cookson, W" uniqKey="Cookson W">W Cookson</name>
</author>
<author>
<name sortKey="Everard, Ml" uniqKey="Everard M">ML Everard</name>
</author>
<author>
<name sortKey="Moffatt, Mf" uniqKey="Moffatt M">MF Moffatt</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Edgar, Rc" uniqKey="Edgar R">RC Edgar</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Caporaso, Jg" uniqKey="Caporaso J">JG Caporaso</name>
</author>
<author>
<name sortKey="Bittinger, K" uniqKey="Bittinger K">K Bittinger</name>
</author>
<author>
<name sortKey="Bushman, Fd" uniqKey="Bushman F">FD Bushman</name>
</author>
<author>
<name sortKey="Desantis, Tz" uniqKey="Desantis T">TZ DeSantis</name>
</author>
<author>
<name sortKey="Andersen, Gl" uniqKey="Andersen G">GL Andersen</name>
</author>
<author>
<name sortKey="Knight, R" uniqKey="Knight R">R Knight</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Desantis, Tz" uniqKey="Desantis T">TZ DeSantis</name>
</author>
<author>
<name sortKey="Hugenholtz, P" uniqKey="Hugenholtz P">P Hugenholtz</name>
</author>
<author>
<name sortKey="Keller, K" uniqKey="Keller K">K Keller</name>
</author>
<author>
<name sortKey="Brodie, El" uniqKey="Brodie E">EL Brodie</name>
</author>
<author>
<name sortKey="Larsen, N" uniqKey="Larsen N">N Larsen</name>
</author>
<author>
<name sortKey="Piceno, Ym" uniqKey="Piceno Y">YM Piceno</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Mcmurdie, Pj" uniqKey="Mcmurdie P">PJ McMurdie</name>
</author>
<author>
<name sortKey="Holmes, S" uniqKey="Holmes S">S Holmes</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Davis, Nm" uniqKey="Davis N">NM Davis</name>
</author>
<author>
<name sortKey="Proctor, Dm" uniqKey="Proctor D">DM Proctor</name>
</author>
<author>
<name sortKey="Holmes, Sp" uniqKey="Holmes S">SP Holmes</name>
</author>
<author>
<name sortKey="Relman, Da" uniqKey="Relman D">DA Relman</name>
</author>
<author>
<name sortKey="Callahan, Bj" uniqKey="Callahan B">BJ Callahan</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Belk, A" uniqKey="Belk A">A Belk</name>
</author>
<author>
<name sortKey="Xu, Zz" uniqKey="Xu Z">ZZ Xu</name>
</author>
<author>
<name sortKey="Carter, Do" uniqKey="Carter D">DO Carter</name>
</author>
<author>
<name sortKey="Lynne, A" uniqKey="Lynne A">A Lynne</name>
</author>
<author>
<name sortKey="Bucheli, S" uniqKey="Bucheli S">S Bucheli</name>
</author>
<author>
<name sortKey="Knight, R" uniqKey="Knight R">R Knight</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Dahl, C" uniqKey="Dahl C">C Dahl</name>
</author>
<author>
<name sortKey="Stanislawski, M" uniqKey="Stanislawski M">M Stanislawski</name>
</author>
<author>
<name sortKey="Iszatt, N" uniqKey="Iszatt N">N Iszatt</name>
</author>
<author>
<name sortKey="Mandal, S" uniqKey="Mandal S">S Mandal</name>
</author>
<author>
<name sortKey="Lozupone, C" uniqKey="Lozupone C">C Lozupone</name>
</author>
<author>
<name sortKey="Clemente, Jc" uniqKey="Clemente J">JC Clemente</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
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<author>
<name sortKey="Sun, Sx" uniqKey="Sun S">SX Sun</name>
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</author>
<author>
<name sortKey="Pedro, H" uniqKey="Pedro H">H Pedro</name>
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<author>
<name sortKey="Cardenas, P" uniqKey="Cardenas P">P Cardenas</name>
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<author>
<name sortKey="Bush, A" uniqKey="Bush A">A Bush</name>
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<author>
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</author>
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<author>
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<author>
<name sortKey="Bittinger, K" uniqKey="Bittinger K">K Bittinger</name>
</author>
<author>
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</author>
<author>
<name sortKey="Fitzgerald, As" uniqKey="Fitzgerald A">AS Fitzgerald</name>
</author>
<author>
<name sortKey="Frank, I" uniqKey="Frank I">I Frank</name>
</author>
<author>
<name sortKey="Yadav, A" uniqKey="Yadav A">A Yadav</name>
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<article-id pub-id-type="pmc">6797130</article-id>
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<subj-group>
<subject>Non-coding RNA</subject>
<subj-group>
<subject>Ribosomal RNA</subject>
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</subj-group>
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<article-title>Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children</article-title>
<alt-title alt-title-type="running-head">Viral respiratory infections and the bacterial microbiota in wheezing children</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-9604-2269</contrib-id>
<name>
<surname>Cuthbertson</surname>
<given-names>Leah</given-names>
</name>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Oo</surname>
<given-names>Stephen W. C.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff003">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cox</surname>
<given-names>Michael J.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Khoo</surname>
<given-names>Siew-Kim</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cox</surname>
<given-names>Des W.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chidlow</surname>
<given-names>Glenys</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Franks</surname>
<given-names>Kimberley</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Prastanti</surname>
<given-names>Franciska</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Borland</surname>
<given-names>Meredith L.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff006">
<sup>6</sup>
</xref>
<xref ref-type="aff" rid="aff007">
<sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gern</surname>
<given-names>James E.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<xref ref-type="aff" rid="aff008">
<sup>8</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Smith</surname>
<given-names>David W.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
<xref ref-type="aff" rid="aff009">
<sup>9</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bizzintino</surname>
<given-names>Joelene A.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-1641-9899</contrib-id>
<name>
<surname>Laing</surname>
<given-names>Ingrid A.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<xref ref-type="aff" rid="aff002">
<sup>
<italic>2</italic>
</sup>
</xref>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Le Souëf</surname>
<given-names>Peter N.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Moffatt</surname>
<given-names>Miriam F.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cookson</surname>
<given-names>William O. C.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff010">
<sup>10</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff001">
<label>1</label>
<addr-line>National Heart and Lung Institute, Imperial College, London, England, United Kingdom</addr-line>
</aff>
<aff id="aff002">
<label>2</label>
<addr-line>Division of Paediatrics, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia</addr-line>
</aff>
<aff id="aff003">
<label>3</label>
<addr-line>Respiratory Department, Perth Children’s Hospital, Perth, Western Australia</addr-line>
</aff>
<aff id="aff004">
<label>4</label>
<addr-line>Telethon Kids Institute, Perth, Australia</addr-line>
</aff>
<aff id="aff005">
<label>5</label>
<addr-line>Department of Microbiology, PathWest Laboratory Medicine WA, QEII Medical Centre, Perth, Australia</addr-line>
</aff>
<aff id="aff006">
<label>6</label>
<addr-line>Emergency Department, Perth Children’s Hospital, Perth, Australia</addr-line>
</aff>
<aff id="aff007">
<label>7</label>
<addr-line>Division of Emergency Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia</addr-line>
</aff>
<aff id="aff008">
<label>8</label>
<addr-line>Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America</addr-line>
</aff>
<aff id="aff009">
<label>9</label>
<addr-line>Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia</addr-line>
</aff>
<aff id="aff010">
<label>10</label>
<addr-line>Royal Brompton and Harefield NHS Foundation Trust, London, England, United Kingdom</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Jin</surname>
<given-names>Dong-Yan</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>University of Hong Kong, HONG KONG</addr-line>
</aff>
<author-notes>
<fn fn-type="COI-statement" id="coi001">
<p>
<bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="other" id="econtrib001">
<p>‡ These authors also contributed equally to this work.</p>
</fn>
<corresp id="cor001">* E-mail:
<email>l.cuthbertson@imperial.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>17</day>
<month>10</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection">
<year>2019</year>
</pub-date>
<volume>14</volume>
<issue>10</issue>
<elocation-id>e0223990</elocation-id>
<history>
<date date-type="received">
<day>17</day>
<month>7</month>
<year>2019</year>
</date>
<date date-type="accepted">
<day>2</day>
<month>10</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>© 2019 Cuthbertson et al</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Cuthbertson et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pone.0223990.pdf"></self-uri>
<abstract>
<p>Acute viral wheeze in children is a major cause of hospitalisation and a major risk factor for the development of asthma. However, the role of the respiratory tract microbiome in the development of acute wheeze is unclear. To investigate whether severe wheezing episodes in children are associated with bacterial dysbiosis in the respiratory tract, oropharyngeal swabs were collected from 109 children with acute wheezing attending the only tertiary paediatric hospital in Perth, Australia. The bacterial community from these samples was explored using next generation sequencing and compared to samples from 75 non-wheezing controls. No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Within the wheezing group, attendance at kindergarten or preschool was however, associated with increased bacterial diversity. Rhinovirus (RV) infection did not have a significant effect on bacterial community composition. A significant difference in bacterial richness was observed between children with RV-A and RV-C infection, however this is likely due to the differences in age group between the patient cohorts. The bacterial community within the oropharynx was found to be diverse and heterogeneous. Age and attendance at day care or kindergarten were important factors in driving bacterial diversity. However, wheeze and viral infection were not found to significantly relate to the bacterial community. Bacterial airway microbiome is highly variable in early life and its role in wheeze remains less clear than viral influences.</p>
</abstract>
<funding-group>
<award-group id="award001">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/501100000925</institution-id>
<institution>National Health and Medical Research Council</institution>
</institution-wrap>
</funding-source>
<award-id>#458513</award-id>
<principal-award-recipient>
<name>
<surname>Moffatt</surname>
<given-names>Miriam F.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award002">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/501100000925</institution-id>
<institution>National Health and Medical Research Council</institution>
</institution-wrap>
</funding-source>
<award-id>#1045760</award-id>
<principal-award-recipient>
<name>
<surname>Cookson</surname>
<given-names>William O. C.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award003">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/501100000952</institution-id>
<institution>Asthma Foundation ACT</institution>
</institution-wrap>
</funding-source>
<principal-award-recipient>
<name>
<surname>Le Souëf</surname>
<given-names>Peter N.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award004">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100004440</institution-id>
<institution>Wellcome Trust</institution>
</institution-wrap>
</funding-source>
<award-id>P40069</award-id>
<principal-award-recipient>
<name>
<surname>Moffatt</surname>
<given-names>Miriam F.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award005">
<funding-source>
<institution>Asmarley trust</institution>
</funding-source>
<principal-award-recipient>
<name>
<surname>Cookson</surname>
<given-names>William O. C.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award006">
<funding-source>
<institution>Telethon research fellowship (AU)</institution>
</funding-source>
<principal-award-recipient>
<name>
<surname>Oo</surname>
<given-names>Stephen W. C.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award007">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100010289</institution-id>
<institution>Princess Margaret Hospital Foundation</institution>
</institution-wrap>
</funding-source>
<principal-award-recipient>
<name>
<surname>Oo</surname>
<given-names>Stephen W. C.</given-names>
</name>
</principal-award-recipient>
</award-group>
<funding-statement>This study was funded by an NHMRC program grant (#458513), NHMRC project grant (#1045760), the West Australian Institute of Medical Research and the Asthma Foundation of Western Australia (AFWA), the Wellcome Trust (P40069) and the Asmarley Trust. Fellowship support was also provided for SWCO (Telethon Research Fellowship and Princess Margaret Hospital Foundation Clinical Fellowship).</funding-statement>
</funding-group>
<counts>
<fig-count count="2"></fig-count>
<table-count count="1"></table-count>
<page-count count="15"></page-count>
</counts>
<custom-meta-group>
<custom-meta id="data-availability">
<meta-name>Data Availability</meta-name>
<meta-value>Sequences were submitted to the European nucleotide database, project number PRJEB32061.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes>
<title>Data Availability</title>
<p>Sequences were submitted to the European nucleotide database, project number PRJEB32061.</p>
</notes>
</front>
<sub-article id="pone.0223990.r001" article-type="aggregated-review-documents">
<front-stub>
<article-id pub-id-type="doi">10.1371/journal.pone.0223990.r001</article-id>
<title-group>
<article-title>Decision Letter 0</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Jin</surname>
<given-names>Dong-Yan</given-names>
</name>
<role>Academic Editor</role>
</contrib>
</contrib-group>
<permissions>
<copyright-statement>© 2019 Dong-Yan Jin</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Dong-Yan Jin</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
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<meta-name>Submission Version</meta-name>
<meta-value>0</meta-value>
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</front-stub>
<body>
<p>
<named-content content-type="letter-date">30 Aug 2019</named-content>
</p>
<p>[EXSCINDED]</p>
<p>PONE-D-19-20152</p>
<p>Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children</p>
<p>PLOS ONE</p>
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<p>Your paper was reviewed by two experts in the field and their comments follow. You need to optimize the analysis and clarify whether the subjects are infected by RSV or another virus as suggested by the two reviewers. We invite you to submit a revised version of the manuscript that addresses these points raised during the review process.</p>
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<p>Reviewer #1: Re. Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children</p>
<p>It is an interesting research study to investigate the association between oral microbiota and acute wheeze in young children, in which the role of oral microbiota in influencing the viral infection, or acute wheeze in changing oral microbial community remains to be estimated. 109 case samples from children with acute wheeze (also paired follow-ups from 17 of these children) and 75 control samples from children without symptoms of wheeze were collected and compared for oral microbiota community and viral infection. Relevant clinical information, such as gender, age, atopy, blood cell counts, and cathelicidin measurements, were analyzed in combination of oral bacterial and viral data.</p>
<p>However, this work could be significantly improved with optimized bioinformatics and biostatistical analyses. The following comments may have the authors attentions:</p>
<p>1. QIIME 1 has been succeeded by QIIME 2 because of outdated workflow of QC control and OTU clustering in QIIME 1. The authors should update their analyses by using QIIME 2 or other pipelines that is more advanced than QIIME 1.9.0. This would ideally use amplicon sequence variants instead of 97% OTUs (see this paper for a discussion of this topic:
<ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/pubmed/28731476">https://www.ncbi.nlm.nih.gov/pubmed/28731476</ext-link>
). Meantime, key parameters of workflow for OTU clustering and taxa assignment would be clearly indicated.</p>
<p>2. The authors used 16S V4 region primers and quantitative PCR to measure oral bacterial biomass. If so, was there baseline control for normalization?</p>
<p>3. The authors used three key measures, including Richness, Shannon-Weiner and Inverse Simpsons, to compare the differences of oral microbiota communities between samples from children with and without acute wheeze. However, more detailed comparison of specific bacteria taxa should be performed to show the differential bacterial composition and abundance between cases and controls. For example, as shown in Figure 1, which bacteria(s) was/were the mostly changed in relative abundance; it could be estimated with LEfSe, Wilcoxon signed rank test or Turkey HSD etc.</p>
<p>4. The age should be one of important factors influencing oral microbial community. Given the wide range of years of children age (0.08-18.5 yeas), the authors should consider to divide the samples into different ago groups and compare the difference of bacterial composition and abundance.</p>
<p>5. Table 1 lacks statistical comparison of demographic information between cases and controls.</p>
<p>6. Figure 1 lacks the basic unit of Biomass. The percentage proportion of abundance should be indicated in the y-axis.</p>
<p>7. Figure 2 - is it possible that the authors try other PCoA method to cluster samples, for example, weighted or unweighted UniFrac methods?</p>
<p>8. The authors mentioned that "Specific care was made not to contaminate samples with any other part of the mouth". Was there more detailed information?</p>
<p>Reviewer #2: The article is very relevant and evaluated viral respiratory infections and the oropharyngeal bacterial microbiota in acutely</p>
<p>wheezing children. Although they concluded that the microbiota is not associated with viral infection and wheeze in children the article discuss important points that deserve to be published.</p>
<p>However, it not clear if the children with bronchiolitis are infected with RSV or other virus. This must be explored in the results and in the conclusion. Other important point is to performed and analysis of family and order of the microbiota comparing children with bronchiolitis and the controls.</p>
<p>Another point that should be explored in the manuscript is breastfeeding and cesarean delivery, that might be influencing the microbiota.</p>
<p>**********</p>
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<p>Reviewer #2: No</p>
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</body>
</sub-article>
<sub-article id="pone.0223990.r002" article-type="author-comment">
<front-stub>
<article-id pub-id-type="doi">10.1371/journal.pone.0223990.r002</article-id>
<title-group>
<article-title>Author response to Decision Letter 0</article-title>
</title-group>
<related-article id="rel-obj002" ext-link-type="doi" xlink:href="10.1371/journal.pone.0223990" related-article-type="editor-report"></related-article>
<custom-meta-group>
<custom-meta>
<meta-name>Submission Version</meta-name>
<meta-value>1</meta-value>
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</custom-meta-group>
</front-stub>
<body>
<p>
<named-content content-type="author-response-date">17 Sep 2019</named-content>
</p>
<p>Dear Dr Jin, </p>
<p>Thank you for your response to our manuscript. We greatly appreciate the reviewers taking the time to consider this paper for publication in PlosOne, and their very helpful suggestions. We have taken all of their remarks into consideration as follows.</p>
<p>Reviewer #1</p>
<p>We note that the Reviewer considers this to be an interesting research study that would be improved by additions to the bioinformatic and biostatistical analyses. Our responses to specific points are: </p>
<p>1. QIIME 1 has been succeeded by QIIME 2 because of outdated workflow of QC control and OTU clustering in QIIME 1. The authors should update their analyses by using QIIME 2 or other pipelines that is more advanced than QIIME 1.9.0. This would ideally use amplicon sequence variants instead of 97% OTUs (see this paper for a discussion of this topic:
<ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/pubmed/28731476">https://www.ncbi.nlm.nih.gov/pubmed/28731476</ext-link>
). Meantime, key parameters of workflow for OTU clustering and taxa assignment would be clearly indicated.</p>
<p>We are aware of the update of QIIME 1.9.0 to QIIME 2, however QIIME 2 does yet not support dual barcoded data. A work around for this is to use internal illumina demultiplexing, but this process involves the removal of reads pre-analysis and is not optimal. We therefore clarified this reason on line 163 in the methods. </p>
<p>The Reviewer is quite right to draw attention to the potential use of amplicon sequence variants (ASVs). However, ASVs have not been universally accepted, and despite arguments for the use of exact sequence variants (ESVs), OTUs remain an appropriate method of analysis for 16S data. The most important reasons for using OTUs over ASVs or ESVs is that they may lead to the over splitting of OTUs and false inflation of diversity. Considering intragenomic heterogeneity it is possible that multiple ESVs may not be coming from distinct taxa. </p>
<p>We therefore acknowledge this debate in line 177 in the discussion by stating “Exact sequence variants (ESVs) may in some circumstances improve identification of microbial taxa, but genomic sequencing of the airway microbiota is at an early stage. In order to avoid over-splitting of taxa and false inflation of diversity, we have taken the conservative approach of using OTUs in our analyses rather than amplicon sequence variants”. </p>
<p>2. The authors used 16S V4 region primers and quantitative PCR to measure oral bacterial biomass. If so, was there baseline control for normalization?</p>
<p>The protocols for performing quantitative PCR (2) have been updated with edits to both the methods and supplementary methods. These updates clarify the procedure used performing oropharyngeal swabs and explain the internal controls implemented during qPCR analysis. Full details of the parameters used for sequencing analysis have been updated in the methods section of the paper on page7, line 148, referencing all parameters used in the analysis.</p>
<p>3. The authors used three key measures, including Richness, Shannon-Weiner and Inverse Simpsons, to compare the differences of oral microbiota communities between samples from children with and without acute wheeze. However, more detailed comparison of specific bacteria taxa should be performed to show the differential bacterial composition and abundance between cases and controls. For example, as shown in Figure 1, which bacteria(s) was/were the mostly changed in relative abundance; it could be estimated with LEfSe, Wilcoxon signed rank test or Turkey HSD etc.</p>
<p>We reported the use of Random Forest modelling in the paper to predict OTUs significantly associated with disease states. These models had low predictive power and the model results were not considered reliable (i.e. there is no great difference between the sample groups). Results of indicator species analysis (line 237) and DeSeq2 differential abundance analysis (line 238) have now been presented alongside these results in in line with the Reviewer’s comments. </p>
<p>Discriminant analysis has many assumptions and restrictions, including equal sample sizes and homogeneity of variance/covariance that do not apply here.</p>
<p>4. The age should be one of important factors influencing oral microbial community. Given the wide range of years of children age (0.08-18.5 yeas), the authors should consider to divide the samples into different ago groups and compare the difference of bacterial composition and abundance.</p>
<p>We agree with reviewer 1, age is an important factor influencing the microbial community in this study. Several analyses were carried out to investigate the effect of age on the microbial community including controlling for age in the investigation of all clinical characteristics. The cohort of children below the age of 5 were investigated, only bacterial biomass was found to be significantly associated with age in this group. Further groups could not be analysed meaningfully due to the uneven distribution of the age data across the study.</p>
<p>5. Table 1 lacks statistical comparison of demographic information between cases and controls.</p>
<p>Statistical comparisons in the form of p-values have been added to Table 1 .</p>
<p>6. Figure 1 lacks the basic unit of Biomass. The percentage proportion of abundance should be indicated in the y-axis.</p>
<p>The units on Figure 1 have been updated to express the units of bacterial biomass.</p>
<p>7. Figure 2 - is it possible that the authors try other PCoA method to cluster samples, for example, weighted or unweighted UniFrac methods?</p>
<p>We thank reviewer one for suggesting alternative methods of clustering samples based on figure 2. Unweighted UniFrac relies on presences /absence data and does not take into account community composition which can be biased toward rare OTUs. On the other hand, weighted UniFrac uses phylogenetic information to infer genetic relationships based on evolutionary assumptions and this may lead to the introduction of errors. </p>
<p>We have created alternative plots using these measures, but our conclusion is that Bray-Curtis dissimilarity is very commonly used for good reasons, and it remains the most easily understood measure for this plot.</p>
<p>8. The authors mentioned that "Specific care was made not to contaminate samples with any other part of the mouth". Was there more detailed information?</p>
<p>The protocols for performing oropharyngeal swabs have been updated with edits to both the methods and supplementary methods (page 7, line 135). </p>
<p>Reviewer #2: </p>
<p>The article is very relevant and evaluated viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children. Although they concluded that the microbiota is not associated with viral infection and wheeze in children the article discuss important points that deserve to be published. </p>
<p>We note with gratitude that the Reviewer considers this to be an interesting research study that would be improved by additions to the bioinformatic and biostatistical analyses. Our responses to specific points are:</p>
<p>1. It not clear if the children with bronchiolitis are infected with RSV or other virus. This must be explored in the results and in the conclusion. Other important point is to performed and analysis of family and order of the microbiota comparing children with bronchiolitis and the controls.</p>
<p>We have clarified the viral results associated with bronchiolitis diagnosis at the time of sampling in the results (line 274) and with reference to figure 1 in the manuscript.</p>
<p>2. Another point that should be explored in the manuscript is breastfeeding and Caesarean delivery, that might be influencing the microbiota.</p>
<p>We now state on page paragraph that “We did not find any differences in the microbiota that were attributable to recorded breastfeeding. No data was available to explore the effect of delivery method in this study.” Page 13, line 251.</p>
<p>Overall, we feel that the paper has been greatly improved by the Reviewers’ suggestions, and we trust these changes meet with your approval. </p>
<p>Regards, </p>
<p>Dr Leah Cuthbertson</p>
<supplementary-material content-type="local-data" id="pone.0223990.s013">
<label>Attachment</label>
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</p>
</caption>
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<caption>
<p>Click here for additional data file.</p>
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</supplementary-material>
</body>
</sub-article>
<sub-article id="pone.0223990.r003" article-type="aggregated-review-documents">
<front-stub>
<article-id pub-id-type="doi">10.1371/journal.pone.0223990.r003</article-id>
<title-group>
<article-title>Decision Letter 1</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Jin</surname>
<given-names>Dong-Yan</given-names>
</name>
<role>Academic Editor</role>
</contrib>
</contrib-group>
<permissions>
<copyright-statement>© 2019 Dong-Yan Jin</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Dong-Yan Jin</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<related-article id="rel-obj003" ext-link-type="doi" xlink:href="10.1371/journal.pone.0223990" related-article-type="reviewed-article"></related-article>
<custom-meta-group>
<custom-meta>
<meta-name>Submission Version</meta-name>
<meta-value>1</meta-value>
</custom-meta>
</custom-meta-group>
</front-stub>
<body>
<p>
<named-content content-type="letter-date">3 Oct 2019</named-content>
</p>
<p>Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children</p>
<p>PONE-D-19-20152R1</p>
<p>Dear Dr. Cuthbertson,</p>
<p>We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.</p>
<p>Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.</p>
<p>Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at
<ext-link ext-link-type="uri" xlink:href="https://www.editorialmanager.com/pone/">https://www.editorialmanager.com/pone/</ext-link>
, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at
<email>authorbilling@plos.org</email>
.</p>
<p>If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact
<email>onepress@plos.org</email>
.</p>
<p>With kind regards,</p>
<p>Dong-Yan Jin</p>
<p>Academic Editor</p>
<p>PLOS ONE</p>
<p>Additional Editor Comments (optional):</p>
<p>Reviewers' comments:</p>
<p>Reviewer's Responses to Questions</p>
<p>
<bold>Comments to the Author</bold>
</p>
<p>1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.</p>
<p>Reviewer #1: All comments have been addressed</p>
<p>Reviewer #2: (No Response)</p>
<p>**********</p>
<p>2. Is the manuscript technically sound, and do the data support the conclusions?</p>
<p>The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. </p>
<p>Reviewer #1: Yes</p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
<p>3. Has the statistical analysis been performed appropriately and rigorously? </p>
<p>Reviewer #1: Yes</p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
<p>4. Have the authors made all data underlying the findings in their manuscript fully available?</p>
<p>The
<ext-link ext-link-type="uri" xlink:href="http://www.plosone.org/static/policies.action#sharing">PLOS Data policy</ext-link>
requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.</p>
<p>Reviewer #1: Yes</p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
<p>5. Is the manuscript presented in an intelligible fashion and written in standard English?</p>
<p>PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.</p>
<p>Reviewer #1: Yes</p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
<p>6. Review Comments to the Author</p>
<p>Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)</p>
<p>Reviewer #1: (No Response)</p>
<p>Reviewer #2: The authors improved the manuscript accepting the suggestions of the Reviewers. All my concerns had been addressed.</p>
<p>**********</p>
<p>7. PLOS authors have the option to publish the peer review history of their article (
<ext-link ext-link-type="uri" xlink:href="https://journals.plos.org/plosone/s/editorial-and-peer-review-process#loc-peer-review-history">what does this mean?</ext-link>
). If published, this will include your full peer review and any attached files.</p>
<p>If you choose “no”, your identity will remain anonymous but your review may still be made public.</p>
<p>
<bold>Do you want your identity to be public for this peer review?</bold>
For information about this choice, including consent withdrawal, please see our
<ext-link ext-link-type="uri" xlink:href="https://www.plos.org/privacy-policy">Privacy Policy</ext-link>
.</p>
<p>Reviewer #1: No</p>
<p>Reviewer #2: No</p>
</body>
</sub-article>
<sub-article id="pone.0223990.r004" article-type="editor-report">
<front-stub>
<article-id pub-id-type="doi">10.1371/journal.pone.0223990.r004</article-id>
<title-group>
<article-title>Acceptance letter</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Jin</surname>
<given-names>Dong-Yan</given-names>
</name>
<role>Academic Editor</role>
</contrib>
</contrib-group>
<permissions>
<copyright-statement>© 2019 Dong-Yan Jin</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Dong-Yan Jin</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<related-article id="rel-obj004" ext-link-type="doi" xlink:href="10.1371/journal.pone.0223990" related-article-type="reviewed-article"></related-article>
</front-stub>
<body>
<p>
<named-content content-type="letter-date">7 Oct 2019</named-content>
</p>
<p>PONE-D-19-20152R1 </p>
<p>Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children </p>
<p>Dear Dr. Cuthbertson:</p>
<p>I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. </p>
<p>If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact
<email>onepress@plos.org</email>
.</p>
<p>For any other questions or concerns, please email
<email>plosone@plos.org</email>
. </p>
<p>Thank you for submitting your work to PLOS ONE.</p>
<p>With kind regards,</p>
<p>PLOS ONE Editorial Office Staff</p>
<p>on behalf of</p>
<p>Prof. Dong-Yan Jin </p>
<p>Academic Editor</p>
<p>PLOS ONE</p>
</body>
</sub-article>
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<li>Australie</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
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<li>Australie-Occidentale</li>
<li>Wisconsin</li>
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<name sortKey="Khoo, Siew Kim" sort="Khoo, Siew Kim" uniqKey="Khoo S" first="Siew-Kim" last="Khoo">Siew-Kim Khoo</name>
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<name sortKey="Laing, Ingrid A" sort="Laing, Ingrid A" uniqKey="Laing I" first="Ingrid A." last="Laing">Ingrid A. Laing</name>
<name sortKey="Le Souef, Peter N" sort="Le Souef, Peter N" uniqKey="Le Souef P" first="Peter N." last="Le Souëf">Peter N. Le Souëf</name>
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<name sortKey="Smith, David W" sort="Smith, David W" uniqKey="Smith D" first="David W." last="Smith">David W. Smith</name>
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