Bacterial biogeography of adult airways in atopic asthma

for the National Heart, Lung and Blood Institute's 'AsthmaNet'

doi:10.1186/s40168-018-0487-3

Bacterial biogeography of adult airways in atopic asthma

for the National Heart, Lung and Blood Institute's 'AsthmaNet'

Medicine

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Background: Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma. Results: Bacterial microbiota in paired protected bronchial brushings (BB; n=45), induced sputum (IS; n=45), oral wash (OW; n=45), and nasal brushings (NB; n=27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p<0.001), compositional similarity was greatest for BB-IS, particularly in AAs and ANAs. The abundance of genera detected in BB correlated with those detected in IS and OW (r median [IQR] 0.869 [0.748-0.942] and 0.822 [0.687-0.909] respectively), but not with those in NB (r=0.004 [-0.003-0.011]). The number of taxa shared between IS-BB and NB-BB was greater in AAs than in HCs (p<0.05) and included taxa previously associated with asthma. Of the genera abundant in NB, only Moraxella correlated positively with abundance in BB; specific members of this genus were shared between the two compartments only in AAs. Relative abundance of Moraxella in NB of AAs correlated negatively with that of Corynebacterium but positively with markers of eosinophilic inflammation in the blood and BAL fluid. The genus, Corynebacterium, trended to dominate all NB samples of HCs but only half of AAs (p=0.07), in whom abundance of this genus was negatively associated with markers of eosinophilic inflammation. Conclusions: Induced sputum is superior to nasal brush or oral wash for assessing bronchial microbiota composition in asthmatic adults. Although compositionally similar to the bronchial microbiota, the microbiota in induced sputum are distinct, reflecting enrichment of oral bacteria. Specific bacterial genera are shared between the nasal and the bronchial mucosa which are associated with markers of systemic and bronchial inflammation.

Original language	English (US)
Article number	104
Journal	Microbiome
Volume	6
Issue number	1
DOIs	https://doi.org/10.1186/s40168-018-0487-3
State	Published - Jun 9 2018

Keywords

Adult asthma
Atopy
Bronchial microbiota
Corynebacterium
Eosinophilic inflammation
Induced sputum microbiota
Lower airways
Moraxella
Nasal microbiota
Oral microbiota
Upper airways

ASJC Scopus subject areas

Microbiology
Microbiology (medical)

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@article{87330535baad4c86bfa37d44ca9e10ef,

title = "Bacterial biogeography of adult airways in atopic asthma",

abstract = "Background: Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma. Results: Bacterial microbiota in paired protected bronchial brushings (BB; n=45), induced sputum (IS; n=45), oral wash (OW; n=45), and nasal brushings (NB; n=27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p<0.001), compositional similarity was greatest for BB-IS, particularly in AAs and ANAs. The abundance of genera detected in BB correlated with those detected in IS and OW (r median [IQR] 0.869 [0.748-0.942] and 0.822 [0.687-0.909] respectively), but not with those in NB (r=0.004 [-0.003-0.011]). The number of taxa shared between IS-BB and NB-BB was greater in AAs than in HCs (p<0.05) and included taxa previously associated with asthma. Of the genera abundant in NB, only Moraxella correlated positively with abundance in BB; specific members of this genus were shared between the two compartments only in AAs. Relative abundance of Moraxella in NB of AAs correlated negatively with that of Corynebacterium but positively with markers of eosinophilic inflammation in the blood and BAL fluid. The genus, Corynebacterium, trended to dominate all NB samples of HCs but only half of AAs (p=0.07), in whom abundance of this genus was negatively associated with markers of eosinophilic inflammation. Conclusions: Induced sputum is superior to nasal brush or oral wash for assessing bronchial microbiota composition in asthmatic adults. Although compositionally similar to the bronchial microbiota, the microbiota in induced sputum are distinct, reflecting enrichment of oral bacteria. Specific bacterial genera are shared between the nasal and the bronchial mucosa which are associated with markers of systemic and bronchial inflammation.",

keywords = "Adult asthma, Atopy, Bronchial microbiota, Corynebacterium, Eosinophilic inflammation, Induced sputum microbiota, Lower airways, Moraxella, Nasal microbiota, Oral microbiota, Upper airways",

author = "{for the National Heart, Lung and Blood Institute's 'AsthmaNet'} and Juliana Durack and Huang, {Yvonne J.} and Snehal Nariya and Christian, {Laura S.} and {Mark Ansel}, K. and Avraham Beigelman and Mario Castro and Dyer, {Anne Marie} and Elliot Israel and Monica Kraft and Martin, {Richard J.} and Mauger, {David T.} and Rosenberg, {Sharon R.} and King, {Tonya S.} and White, {Steven R.} and Denlinger, {Loren C.} and Fernando Holguin and Lazarus, {Stephen C.} and Njira Lugogo and Peters, {Stephen P.} and Smith, {Lewis J.} and Wechsler, {Michael E.} and Lynch, {Susan V.} and Boushey, {Homer A.} and Robert Pedicini and Kathy Zheng and Duanny Alva and Assel Biyasheva and Jenny Hixon and Lucius Robinson and Mary Gill and Good, {James T.} and Christena Kolakowski and Allen Stevens and {Rand Sutherland}, E. and Julia Bach and Rich Cornwell and Holly Eversoll and Tiffany Huard and Keith Meyer and Barbara Miller and Ann Sexton and Michele Wolff and Merritt Fajt and Sherri Hill and Lisa Lane and Russell Traister and Cathy Vitari and Vanessa Curtis and Brenda Patterson",

note = "Funding Information: This study was supported by National Heart, Lung, and Blood Institute (NHLBI)/AsthmaNet [HL098107] and National Institute of Allergy and Infectious Disease (NIAID)/Inner City Asthma Consortium (ICAC) [AI114271]. YJH was supported by NIAID 1R01AI129958 and NHLBI 1R03HL138310. Funding Information: JD has no conflict of interest. YJH has received grants from the NHLBI, NIAID, and the Michigan Institute of Health and Clinical Research; has received travel and lodging compensation from the NIH and National Academy of Science; and has received payment for lectures from the American Academy of Allergy, Asthma & Immunology; the Massachusetts Institute of Technology; the European Respiratory Society; the Microbiome R&D Business Forum; and the European Academy of Allergy, Asthma, and Clinical Immunology. SN has no conflict of interest. LSC has no conflict of interest. KMA has no conflict of interest. AB reports grants from NHLBI. MC reports grants from NIH, ALA; personal fees from Astra-Zeneca, Aviragen, Boehringer-Ingelheim, Boston Scientific, Elsevier, 4DPharma, Genentech, Mallinckrodt, Neutronic, Nuvaira, Teva, Theravance and VIDA; and grants from Boehringer-Ingelheim, Chiesi, Gilead, Novartis, Sanofi-Aventis, Vectura (all unrelated to the current work). AMD reports grants from NHLBI. EI reports personal fees from AstraZeneca, Novartis, Philips, Respironics, Regeneron Pharmaceuticals, Research in Real Life (RiRL), TEVA Specialty Pharmaceuticals, Bird Rock Bio, Nuvelution, Pharmaceuticals, Vitaeris, Inc., Sanofi, Merck, Entrinsic Health Solutions and GlaxoSmithKline; non-financial support from Boehringer Ingelheim, GlaxoSmithKline, Merck, Sunovion and TEVA Specialty Pharmaceuticals; and grants from Sanofi, Genentech and Boehringer Ingelheim. MK reports grants from NIH; personal fees from Teva Pharmaceuticals, Astra Zenec, FDA LABA Trials Joint DSMB and Elsevier; and grants from Chiesi and Sanofi. RJM reports grants from NIH; personal fees from AstraZeneca, PMD Healthcare and Respiratory Effectiveness Group; and grants from MedImmune and CHiesi FarmaceuticiSpA. DTM reports grants from NIH and non-financial support from GlaxoSmithKIlne, Merck and Boehringer Ingelheim. SRR reports grants from NIH. TSK reports grants from NIH and personal fees from Pearl Therapeutics, KaloBios, and Insmed Inc. SRW reports grants from NIH. LCD reports grants from NIH and personal fees from Sanofi and GSK. FH has no conflict of interest. SCL reports grants from NIH. NL reports personal fees from TEVA, Astrazeneca and GSK and grants from GSK, SANOFI and AstraZeneca. SPP reports grants from NIH. LJS reports grants from NIH and personal fees from Merck. MEW reports personal fees from AstraZeneca, BSCI, Novartis, Sanofi, Vectura, Regeneron, Meda, Mylan, Gilacure, Tunitas, Genentech, Theravance, Neurotronic, Sentien, Teva, Boehringer INgelheim, GlaxoSmithKline and grants from Sanofi and GlaxoSmithKlin. SVL reports grants from NIH/NIAID, NIH/NICHD, NIH/Office of the Director, NIH/NIDA, Broad Foundation, NIH/ NIAID, Sloan Foundation, Pfizer Inc., Gilead Sciences and Janssen; personal fees from Janssen, Boston Consulting Group, Regeneron, MedImmune, Siolta Therapeutics; has a patent Reductive prodrug cancer chemothera (Stan449-PRV) issued, a patent Combination antibiotic and antibody therapy for the treatment of Pseudomonas aeruginosa infection (WO 2010091189 A1) with royalties paid to KaloBios Inc., a patent Therapeutic microbial consortium for induction of immune tolerance with royalties paid to Siolta Therapeutics, a patent Systems and methods for detecting antibiotic resistance (WO 2012027302 A3) issued, a patent Nitroreductase enzymes (US 7687474 B2) issued, a patent Sinusitis diagnostics and treatments (WO 2013155370 A1) issued, and a patent Methods and systems for phylogenetic analysis (US 20120264637 A1) issued; has Co-founded Siolta Therapeutics and is currently a board member and paid consultant for the company; and owns 25% stock. HAB has received grants including travel and lodging compensation from the NIH/NHBI and the NIH/ NIAID and has received royalty payments from the McGraw-Hill Companies; he is a consultant for Siolta Therapeutics, Inc. of San Francisco, CA.",

year = "2018",

month = jun,

day = "9",

doi = "10.1186/s40168-018-0487-3",

language = "English (US)",

volume = "6",

journal = "Microbiome",

issn = "2049-2618",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Bacterial biogeography of adult airways in atopic asthma

AU - for the National Heart, Lung and Blood Institute's 'AsthmaNet'

AU - Durack, Juliana

AU - Huang, Yvonne J.

AU - Nariya, Snehal

AU - Christian, Laura S.

AU - Mark Ansel, K.

AU - Beigelman, Avraham

AU - Castro, Mario

AU - Dyer, Anne Marie

AU - Israel, Elliot

AU - Kraft, Monica

AU - Martin, Richard J.

AU - Mauger, David T.

AU - Rosenberg, Sharon R.

AU - King, Tonya S.

AU - White, Steven R.

AU - Denlinger, Loren C.

AU - Holguin, Fernando

AU - Lazarus, Stephen C.

AU - Lugogo, Njira

AU - Peters, Stephen P.

AU - Smith, Lewis J.

AU - Wechsler, Michael E.

AU - Lynch, Susan V.

AU - Boushey, Homer A.

AU - Pedicini, Robert

AU - Zheng, Kathy

AU - Alva, Duanny

AU - Biyasheva, Assel

AU - Hixon, Jenny

AU - Robinson, Lucius

AU - Gill, Mary

AU - Good, James T.

AU - Kolakowski, Christena

AU - Stevens, Allen

AU - Rand Sutherland, E.

AU - Bach, Julia

AU - Cornwell, Rich

AU - Eversoll, Holly

AU - Huard, Tiffany

AU - Meyer, Keith

AU - Miller, Barbara

AU - Sexton, Ann

AU - Wolff, Michele

AU - Fajt, Merritt

AU - Hill, Sherri

AU - Lane, Lisa

AU - Traister, Russell

AU - Vitari, Cathy

AU - Curtis, Vanessa

AU - Patterson, Brenda

N1 - Funding Information: This study was supported by National Heart, Lung, and Blood Institute (NHLBI)/AsthmaNet [HL098107] and National Institute of Allergy and Infectious Disease (NIAID)/Inner City Asthma Consortium (ICAC) [AI114271]. YJH was supported by NIAID 1R01AI129958 and NHLBI 1R03HL138310. Funding Information: JD has no conflict of interest. YJH has received grants from the NHLBI, NIAID, and the Michigan Institute of Health and Clinical Research; has received travel and lodging compensation from the NIH and National Academy of Science; and has received payment for lectures from the American Academy of Allergy, Asthma & Immunology; the Massachusetts Institute of Technology; the European Respiratory Society; the Microbiome R&D Business Forum; and the European Academy of Allergy, Asthma, and Clinical Immunology. SN has no conflict of interest. LSC has no conflict of interest. KMA has no conflict of interest. AB reports grants from NHLBI. MC reports grants from NIH, ALA; personal fees from Astra-Zeneca, Aviragen, Boehringer-Ingelheim, Boston Scientific, Elsevier, 4DPharma, Genentech, Mallinckrodt, Neutronic, Nuvaira, Teva, Theravance and VIDA; and grants from Boehringer-Ingelheim, Chiesi, Gilead, Novartis, Sanofi-Aventis, Vectura (all unrelated to the current work). AMD reports grants from NHLBI. EI reports personal fees from AstraZeneca, Novartis, Philips, Respironics, Regeneron Pharmaceuticals, Research in Real Life (RiRL), TEVA Specialty Pharmaceuticals, Bird Rock Bio, Nuvelution, Pharmaceuticals, Vitaeris, Inc., Sanofi, Merck, Entrinsic Health Solutions and GlaxoSmithKline; non-financial support from Boehringer Ingelheim, GlaxoSmithKline, Merck, Sunovion and TEVA Specialty Pharmaceuticals; and grants from Sanofi, Genentech and Boehringer Ingelheim. MK reports grants from NIH; personal fees from Teva Pharmaceuticals, Astra Zenec, FDA LABA Trials Joint DSMB and Elsevier; and grants from Chiesi and Sanofi. RJM reports grants from NIH; personal fees from AstraZeneca, PMD Healthcare and Respiratory Effectiveness Group; and grants from MedImmune and CHiesi FarmaceuticiSpA. DTM reports grants from NIH and non-financial support from GlaxoSmithKIlne, Merck and Boehringer Ingelheim. SRR reports grants from NIH. TSK reports grants from NIH and personal fees from Pearl Therapeutics, KaloBios, and Insmed Inc. SRW reports grants from NIH. LCD reports grants from NIH and personal fees from Sanofi and GSK. FH has no conflict of interest. SCL reports grants from NIH. NL reports personal fees from TEVA, Astrazeneca and GSK and grants from GSK, SANOFI and AstraZeneca. SPP reports grants from NIH. LJS reports grants from NIH and personal fees from Merck. MEW reports personal fees from AstraZeneca, BSCI, Novartis, Sanofi, Vectura, Regeneron, Meda, Mylan, Gilacure, Tunitas, Genentech, Theravance, Neurotronic, Sentien, Teva, Boehringer INgelheim, GlaxoSmithKline and grants from Sanofi and GlaxoSmithKlin. SVL reports grants from NIH/NIAID, NIH/NICHD, NIH/Office of the Director, NIH/NIDA, Broad Foundation, NIH/ NIAID, Sloan Foundation, Pfizer Inc., Gilead Sciences and Janssen; personal fees from Janssen, Boston Consulting Group, Regeneron, MedImmune, Siolta Therapeutics; has a patent Reductive prodrug cancer chemothera (Stan449-PRV) issued, a patent Combination antibiotic and antibody therapy for the treatment of Pseudomonas aeruginosa infection (WO 2010091189 A1) with royalties paid to KaloBios Inc., a patent Therapeutic microbial consortium for induction of immune tolerance with royalties paid to Siolta Therapeutics, a patent Systems and methods for detecting antibiotic resistance (WO 2012027302 A3) issued, a patent Nitroreductase enzymes (US 7687474 B2) issued, a patent Sinusitis diagnostics and treatments (WO 2013155370 A1) issued, and a patent Methods and systems for phylogenetic analysis (US 20120264637 A1) issued; has Co-founded Siolta Therapeutics and is currently a board member and paid consultant for the company; and owns 25% stock. HAB has received grants including travel and lodging compensation from the NIH/NHBI and the NIH/ NIAID and has received royalty payments from the McGraw-Hill Companies; he is a consultant for Siolta Therapeutics, Inc. of San Francisco, CA.

PY - 2018/6/9

Y1 - 2018/6/9

N2 - Background: Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma. Results: Bacterial microbiota in paired protected bronchial brushings (BB; n=45), induced sputum (IS; n=45), oral wash (OW; n=45), and nasal brushings (NB; n=27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p<0.001), compositional similarity was greatest for BB-IS, particularly in AAs and ANAs. The abundance of genera detected in BB correlated with those detected in IS and OW (r median [IQR] 0.869 [0.748-0.942] and 0.822 [0.687-0.909] respectively), but not with those in NB (r=0.004 [-0.003-0.011]). The number of taxa shared between IS-BB and NB-BB was greater in AAs than in HCs (p<0.05) and included taxa previously associated with asthma. Of the genera abundant in NB, only Moraxella correlated positively with abundance in BB; specific members of this genus were shared between the two compartments only in AAs. Relative abundance of Moraxella in NB of AAs correlated negatively with that of Corynebacterium but positively with markers of eosinophilic inflammation in the blood and BAL fluid. The genus, Corynebacterium, trended to dominate all NB samples of HCs but only half of AAs (p=0.07), in whom abundance of this genus was negatively associated with markers of eosinophilic inflammation. Conclusions: Induced sputum is superior to nasal brush or oral wash for assessing bronchial microbiota composition in asthmatic adults. Although compositionally similar to the bronchial microbiota, the microbiota in induced sputum are distinct, reflecting enrichment of oral bacteria. Specific bacterial genera are shared between the nasal and the bronchial mucosa which are associated with markers of systemic and bronchial inflammation.

AB - Background: Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma. Results: Bacterial microbiota in paired protected bronchial brushings (BB; n=45), induced sputum (IS; n=45), oral wash (OW; n=45), and nasal brushings (NB; n=27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p<0.001), compositional similarity was greatest for BB-IS, particularly in AAs and ANAs. The abundance of genera detected in BB correlated with those detected in IS and OW (r median [IQR] 0.869 [0.748-0.942] and 0.822 [0.687-0.909] respectively), but not with those in NB (r=0.004 [-0.003-0.011]). The number of taxa shared between IS-BB and NB-BB was greater in AAs than in HCs (p<0.05) and included taxa previously associated with asthma. Of the genera abundant in NB, only Moraxella correlated positively with abundance in BB; specific members of this genus were shared between the two compartments only in AAs. Relative abundance of Moraxella in NB of AAs correlated negatively with that of Corynebacterium but positively with markers of eosinophilic inflammation in the blood and BAL fluid. The genus, Corynebacterium, trended to dominate all NB samples of HCs but only half of AAs (p=0.07), in whom abundance of this genus was negatively associated with markers of eosinophilic inflammation. Conclusions: Induced sputum is superior to nasal brush or oral wash for assessing bronchial microbiota composition in asthmatic adults. Although compositionally similar to the bronchial microbiota, the microbiota in induced sputum are distinct, reflecting enrichment of oral bacteria. Specific bacterial genera are shared between the nasal and the bronchial mucosa which are associated with markers of systemic and bronchial inflammation.

KW - Adult asthma

KW - Atopy

KW - Bronchial microbiota

KW - Corynebacterium

KW - Eosinophilic inflammation

KW - Induced sputum microbiota

KW - Lower airways

KW - Moraxella

KW - Nasal microbiota

KW - Oral microbiota

KW - Upper airways

UR - http://www.scopus.com/inward/record.url?scp=85048320619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048320619&partnerID=8YFLogxK

U2 - 10.1186/s40168-018-0487-3

DO - 10.1186/s40168-018-0487-3

M3 - Article

C2 - 29885665

AN - SCOPUS:85048320619

VL - 6

JO - Microbiome

JF - Microbiome

SN - 2049-2618

IS - 1

M1 - 104

ER -