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

Abstract

BackgroundLower respiratory tract infections (LRTIs) are the leading cause of infant morbidity and mortality worldwide, and altered metabolite production is recognized as a critical factor in LRTI pathogenesis.MethodsThis 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.ResultsWe 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 (XU) ratio at birth predicted a four-fold increased LRTI risk.ConclusionThis 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.