Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis

B T Kopp; E Joseloff; D Goetz; B Ingram; S L Heltshe; D H Leung; B W Ramsey; K McCoy; D Borowitz

doi:10.1016/j.jcf.2018.10.016

Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis

J Cyst Fibros. 2019 Jul;18(4):507-515. doi: 10.1016/j.jcf.2018.10.016. Epub 2018 Nov 23.

Authors

B T Kopp¹, E Joseloff², D Goetz³, B Ingram⁴, S L Heltshe⁵, D H Leung⁶, B W Ramsey⁵, K McCoy⁷, D Borowitz⁸

Affiliations

¹ Division of Pulmonary Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Center for Microbial Pathogenesis, Nationwide Children's Hospital, Columbus, OH, USA. Electronic address: Benjamin.Kopp@NationwideChildrens.org.
² Cystic Fibrosis Foundation, Bethesda, MD, USA.
³ Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
⁴ Metabolon Inc., Durham, NC, USA.
⁵ Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA, USA; University of Washington, Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Seattle, WA, USA.
⁶ Department of Pediatrics, Baylor College of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, Houston, TX, USA.
⁷ Division of Pulmonary Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
⁸ Cystic Fibrosis Foundation, Bethesda, MD, USA; Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

Abstract

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).

Keywords: Biomarkers; CF; Metabolites.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cystic Fibrosis / complications
Cystic Fibrosis / metabolism
Cystic Fibrosis / urine*
Female
Humans
Infant
Male
Metabolic Networks and Pathways
Metabolomics*
Nutritional Status
Prospective Studies

Associated data

ClinicalTrials.gov/NCT01424696

Abstract

Publication types

MeSH terms

Associated data

Grants and funding