Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis.
Biomarkers
CF
Metabolites
Journal
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
01
08
2018
revised:
25
10
2018
accepted:
28
10
2018
pubmed:
28
11
2018
medline:
18
9
2020
entrez:
28
11
2018
Statut:
ppublish
Résumé
Biologic pathways and metabolic mechanisms underpinning early systemic disease in cystic fibrosis (CF) are poorly understood. The Baby Observational and Nutrition Study (BONUS) was a prospective multi-center study of infants with CF with a primary aim to examine the current state of nutrition in the first year of life. Its secondary aim was to prospectively explore concurrent nutritional, metabolic, respiratory, infectious, and inflammatory characteristics associated with early CF anthropometric measurements. We report here metabolomics differences within the urine of these infants as compared to infants without CF. Urine metabolomics was performed for 85 infants with predefined clinical phenotypes at approximately one year of age enrolled in BONUS via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Samples were stratified by disease status (non-CF controls (n = 22); CF (n = 63, All-CF)) and CF clinical phenotype: respiratory hospitalization (CF Resp, n = 22), low length (CF LL, n = 23), and low weight (CF LW, n = 15). Global urine metabolomics profiles in CF were heterogeneous, however there were distinct metabolic differences between the CF and non-CF groups. Top pathways altered in CF included tRNA charging and methionine degradation. ADCYAP1 and huntingtin were identified as predicted unique regulators of altered metabolic pathways in CF compared to non-CF. Infants with CF displayed alterations in metabolites associated with bile acid homeostasis, pentose sugars, and vitamins. Predicted metabolic pathways and regulators were identified in CF infants compared to non-CF, but metabolic profiles were unable to discriminate between CF phenotypes. Targeted metabolomics provides an opportunity for further understanding of early CF disease. United States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).
Sections du résumé
BACKGROUND
Biologic pathways and metabolic mechanisms underpinning early systemic disease in cystic fibrosis (CF) are poorly understood. The Baby Observational and Nutrition Study (BONUS) was a prospective multi-center study of infants with CF with a primary aim to examine the current state of nutrition in the first year of life. Its secondary aim was to prospectively explore concurrent nutritional, metabolic, respiratory, infectious, and inflammatory characteristics associated with early CF anthropometric measurements. We report here metabolomics differences within the urine of these infants as compared to infants without CF.
METHODS
Urine metabolomics was performed for 85 infants with predefined clinical phenotypes at approximately one year of age enrolled in BONUS via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Samples were stratified by disease status (non-CF controls (n = 22); CF (n = 63, All-CF)) and CF clinical phenotype: respiratory hospitalization (CF Resp, n = 22), low length (CF LL, n = 23), and low weight (CF LW, n = 15).
RESULTS
Global urine metabolomics profiles in CF were heterogeneous, however there were distinct metabolic differences between the CF and non-CF groups. Top pathways altered in CF included tRNA charging and methionine degradation. ADCYAP1 and huntingtin were identified as predicted unique regulators of altered metabolic pathways in CF compared to non-CF. Infants with CF displayed alterations in metabolites associated with bile acid homeostasis, pentose sugars, and vitamins.
CONCLUSIONS
Predicted metabolic pathways and regulators were identified in CF infants compared to non-CF, but metabolic profiles were unable to discriminate between CF phenotypes. Targeted metabolomics provides an opportunity for further understanding of early CF disease.
TRIAL REGISTRATION
United States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).
Identifiants
pubmed: 30477895
pii: S1569-1993(18)30916-0
doi: 10.1016/j.jcf.2018.10.016
pmc: PMC6533170
mid: NIHMS1514345
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT01424696']
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
507-515Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK089507
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK095738
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Références
Science. 2001 May 25;292(5521):1552-5
pubmed: 11375494
J Pediatr. 1964 Oct;65:480-94
pubmed: 14216638
Br J Pharmacol. 2004 Feb;141(4):698-708
pubmed: 14744818
Biomarkers. 2009 Feb;14(1):55-60
pubmed: 19283525
Pediatr Res. 2010 Jul;68(1):75-80
pubmed: 20351658
J Biol Chem. 2010 Oct 1;285(40):30516-22
pubmed: 20675369
MMWR Recomm Rep. 2010 Sep 10;59(RR-9):1-15
pubmed: 20829749
Am J Respir Crit Care Med. 2011 Jul 1;184(1):75-81
pubmed: 21493738
Thorax. 2012 Mar;67(3):222-8
pubmed: 22106016
Clin Pediatr (Phila). 2012 Sep;51(9):852-5
pubmed: 22718704
Pediatr Pulmonol. 2014 May;49(5):463-72
pubmed: 23847148
Am J Respir Crit Care Med. 2014 Jul 15;190(2):229-33
pubmed: 25025356
Chest. 2015 Aug;148(2):507-515
pubmed: 25611918
Clin Transl Sci. 2015 Aug;8(4):330-3
pubmed: 26053284
Pediatr Pulmonol. 2015 Sep;50(9):869-77
pubmed: 26115542
Mol Cell Pediatr. 2015 Dec;2(1):9
pubmed: 26542299
ISME J. 2016 Jun;10(6):1483-98
pubmed: 26623545
Sci Rep. 2016 Jul 19;6:29768
pubmed: 27432520
Pediatr Clin North Am. 2016 Aug;63(4):599-615
pubmed: 27469178
PeerJ. 2016 Aug 11;4:e2174
pubmed: 27602256
J Biol Chem. 2016 Dec 2;291(49):25489-25504
pubmed: 27756846
Eur Respir J. 2016 Dec;48(6):1612-1621
pubmed: 27836957
J Cyst Fibros. 2017 Mar;16(2):214-221
pubmed: 27889352
Arch Pediatr. 2016 Dec;23(12S):12S15-12S20
pubmed: 28231889
Metabolism. 2017 May;70:31-41
pubmed: 28403943
JAMA Pediatr. 2017 Jun 1;171(6):546-554
pubmed: 28437538
Presse Med. 2017 Jun;46(6 Pt 2):e139-e164
pubmed: 28576636
Pediatr Pulmonol. 2017 Nov;52(S48):S4-S14
pubmed: 28881097
Cell Host Microbe. 2017 Nov 8;22(5):705-716.e4
pubmed: 29056429
Respir Res. 2018 Jan 08;19(1):6
pubmed: 29310632
Front Pediatr. 2018 Jan 10;5:290
pubmed: 29376041
Pediatr Pulmonol. 2018 May;53(5):583-591
pubmed: 29461009