Purine degradation pathway metabolites at birth and the risk of lower respiratory tract infections in infancy

Authors

Maria J. Gutierrez, Division of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Gustavo Nino, Division of Pulmonary and Sleep Medicine, Children's National Hospital, George Washington University, Washington, DC, USA.
Sonia Restrepo-Gualteros, Department of Pediatrics, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia.
Ethan Mondell, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Elizabeth Chorvinsky, Center for Genetic Medicine Research, Children's Research Institute, Washington, DC, USA.
Surajit Bhattacharya, Center for Genetic Medicine Research, Children's Research Institute, Washington, DC, USA.
Bethlehem Solomon Bera, Center for Genetic Medicine Research, Children's Research Institute, Washington, DC, USA.
Allison Welham, Center for Genetic Medicine Research, Children's Research Institute, Washington, DC, USA.
Xiumei Hong, Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Xiaobin Wang, Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Document Type

Journal Article

Publication Date

1-1-2024

Journal

ERJ open research

Volume

10

Issue

1

DOI

10.1183/23120541.00693-2023

Abstract

BACKGROUND: Lower respiratory tract infections (LRTIs) are the leading cause of infant morbidity and mortality worldwide, and altered metabolite production is recognised as a critical factor in LRTI pathogenesis. METHODS: This study aimed to identify prenatal metabolic changes associated with LRTI risk in infancy, using liquid chromatography-mass spectrometry unbiased metabolomics analysis on cord blood from 810 full-term newborns. RESULTS: We identified 22 compounds linked to LRTIs in infancy, enriched for purine degradation pathway (PDP) metabolites. High cord blood PDP metabolites, including xanthine, hypoxanthine, xanthosine and inosine, were linked to reduced LRTI risk during infancy. Notably, a low xanthine to uric acid ratio at birth predicted a four-fold increased LRTI risk. CONCLUSION: This study is the first to reveal that high cord blood PDP metabolites identify newborns at lower LRTI risk, stratifying disease risk at birth. Moreover, our results prompt further study on PDP enzymes as pharmacological targets to decrease LRTI morbidity and mortality for at-risk newborns.

APA Citation

Gutierrez, Maria J.; Nino, Gustavo; Restrepo-Gualteros, Sonia; Mondell, Ethan; Chorvinsky, Elizabeth; Bhattacharya, Surajit; Bera, Bethlehem Solomon; Welham, Allison; Hong, Xiumei; and Wang, Xiaobin, "Purine degradation pathway metabolites at birth and the risk of lower respiratory tract infections in infancy" (2024). GW Authored Works. Paper 4307.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4307

Department

Pediatrics