Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis.

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).