Serum Metabolome Is Associated With the Nasopharyngeal Microbiota and Disease Severity Among Infants With Bronchiolitis.
Bronchiolitis
metabolomics
microbiota
serum
severity
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
24 05 2019
24 05 2019
Historique:
received:
22
11
2018
accepted:
08
01
2019
pubmed:
11
1
2019
medline:
3
3
2020
entrez:
11
1
2019
Statut:
ppublish
Résumé
Emerging evidence suggests relationships between the nasopharyngeal metabolome and both the microbiota and severity of bronchiolitis. However, the influence of host systemic metabolism on disease pathobiology remains unclear. We aimed to examine metabolome profiles and their association with more-severe disease, defined by use of positive pressure ventilation (PPV), in infants hospitalized for bronchiolitis. In 140 infants with bronchiolitis, metabolomic profiling was performed on serum; samples from 70 were in a training data set, and samples from 70 were in an independent test data set. We also profiled the nasopharyngeal airway microbiota and examined its association with the serum metabolites. Serum metabolome profiles differed by bronchiolitis severity (P < .001). In total, 20 metabolites in the training data set were significantly associated with the risk of PPV, of which 18 remained significant following adjustment for confounders (false-discovery rate [FDR], < 0.10). Phosphatidylcholine metabolites were associated with higher risks of PPV use, while metabolites from the plasmalogen subpathway were associated with lower risks. The test data set validated these findings (FDR < 0.05). Streptococcus abundance was positively associated with metabolites that are associated with higher risks of PPV. Serum metabolomic signatures were associated with both the nasopharyngeal microbiota and the severity of bronchiolitis. Our findings advance research into the complex interrelations between the airway microbiome, host systemic response, and pathobiology of bronchiolitis.
Sections du résumé
BACKGROUND
Emerging evidence suggests relationships between the nasopharyngeal metabolome and both the microbiota and severity of bronchiolitis. However, the influence of host systemic metabolism on disease pathobiology remains unclear. We aimed to examine metabolome profiles and their association with more-severe disease, defined by use of positive pressure ventilation (PPV), in infants hospitalized for bronchiolitis.
METHODS
In 140 infants with bronchiolitis, metabolomic profiling was performed on serum; samples from 70 were in a training data set, and samples from 70 were in an independent test data set. We also profiled the nasopharyngeal airway microbiota and examined its association with the serum metabolites.
RESULTS
Serum metabolome profiles differed by bronchiolitis severity (P < .001). In total, 20 metabolites in the training data set were significantly associated with the risk of PPV, of which 18 remained significant following adjustment for confounders (false-discovery rate [FDR], < 0.10). Phosphatidylcholine metabolites were associated with higher risks of PPV use, while metabolites from the plasmalogen subpathway were associated with lower risks. The test data set validated these findings (FDR < 0.05). Streptococcus abundance was positively associated with metabolites that are associated with higher risks of PPV.
CONCLUSIONS
Serum metabolomic signatures were associated with both the nasopharyngeal microbiota and the severity of bronchiolitis. Our findings advance research into the complex interrelations between the airway microbiome, host systemic response, and pathobiology of bronchiolitis.
Identifiants
pubmed: 30629185
pii: 5285940
doi: 10.1093/infdis/jiz021
pmc: PMC6534192
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2005-2014Subventions
Organisme : NIAID NIH HHS
ID : R01 AI127507
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI108588
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134940
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI087881
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137091
Pays : United States
Organisme : NIH HHS
ID : UG3 OD023253
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL129909
Pays : United States
Organisme : NIH HHS
ID : UH3 OD023253
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Références
BMC Res Notes. 2017 Jul 26;10(1):325
pubmed: 28747215
J Infect Dis. 2016 Dec 15;214(12):1924-1928
pubmed: 27923952
Front Microbiol. 2015 Oct 07;6:1085
pubmed: 26500629
J Infect Dis. 2018 Mar 13;217(7):1160-1169
pubmed: 29293990
Mol Aspects Med. 2009 Feb-Apr;30(1-2):60-76
pubmed: 18760298
Cell Host Microbe. 2015 May 13;17(5):704-15
pubmed: 25865368
Chest. 2017 Feb;151(2):262-277
pubmed: 27776981
Lancet. 2010 May 1;375(9725):1545-55
pubmed: 20399493
Neuroscientist. 2001 Jun;7(3):232-45
pubmed: 11499402
Nucleic Acids Res. 2015 Jul 1;43(W1):W251-7
pubmed: 25897128
PLoS One. 2015 May 13;10(5):e0127098
pubmed: 25970287
Bioinformatics. 2009 Nov 1;25(21):2855-6
pubmed: 19706745
Nature. 2012 Jun 13;486(7402):207-14
pubmed: 22699609
Clin Respir J. 2017 Nov;11(6):839-846
pubmed: 26663823
Pediatrics. 2016 Jul;138(1):
pubmed: 27354456
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3698-703
pubmed: 19234110
Biochim Biophys Acta. 2012 Sep;1822(9):1442-52
pubmed: 22627108
Nat Med. 2014 Feb;20(2):159-66
pubmed: 24390308
Expert Rev Respir Med. 2016 Aug;10(8):891-9
pubmed: 27192374
Am J Respir Crit Care Med. 2016 Nov 1;194(9):1104-1115
pubmed: 27135599
Am J Physiol Heart Circ Physiol. 2002 Aug;283(2):H671-9
pubmed: 12124215
Crit Care Med. 2000 May;28(5):1572-7
pubmed: 10834714
J Allergy Clin Immunol. 2015 Aug;136(2):509-12.e11
pubmed: 25840721
Pediatrics. 2013 Jul;132(1):28-36
pubmed: 23733801
Am J Respir Crit Care Med. 2017 Oct 1;196(7):882-891
pubmed: 28530140
Pediatrics. 2014 Nov;134(5):e1474-502
pubmed: 25349312
Eur Respir J. 2016 Nov;48(5):1329-1339
pubmed: 27799386
PLoS One. 2014 Oct 21;9(10):e111228
pubmed: 25333938
Am J Respir Cell Mol Biol. 2016 May;54(5):609-17
pubmed: 26949916
Front Microbiol. 2016 Jul 26;7:1144
pubmed: 27507964
Clin Infect Dis. 2017 Sep 15;65(6):967-975
pubmed: 28541502
J Allergy Clin Immunol. 2016 Jun;137(6):1909-1913.e4
pubmed: 27061249
Anal Chem. 2006 Jan 15;78(2):567-74
pubmed: 16408941
J Infect Dis. 2015 May 15;211(10):1550-9
pubmed: 25425699
Am J Physiol Lung Cell Mol Physiol. 2005 Feb;288(2):L379-83
pubmed: 15501950
Allergy. 2017 Nov;72(11):1796-1800
pubmed: 28306146
PLoS One. 2008;3(12):e3863
pubmed: 19057651