TY - JOUR
T1 - Metabolomic Analysis Reveals the Association of Severe Bronchopulmonary Dysplasia with Gut Microbiota and Oxidative Response in Extremely Preterm Infants
AU - Chiu, Chih Yung
AU - Chiang, Ming Chou
AU - Chiang, Meng Han
AU - Lien, Reyin
AU - Fu, Ren Huei
AU - Hsu, Kai Hsiang
AU - Chu, Shih Ming
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/4/13
Y1 - 2024/4/13
N2 - Bronchopulmonary dysplasia (BPD) is a chronic lung disease mainly affecting premature infants needing ventilation or oxygen for respiratory distress. This study aimed to evaluate the molecular linkages for BPD in very and extremely preterm infants using a metabolomics-based approach. A case-control study of enrolling preterm infants born before 32 weeks gestational age (GA) was prospectively performed. These preterm infants were subsequently stratified into the following two groups for further analysis: no or mild BPD, and moderate or severe BPD based on the 2019 NICHD criteria. Urinary metabolomic profiling was performed using 1H-Nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA) at a corrected age of 6 months. Metabolites significantly differentially related to GA and BPD severity were performed between groups, and their roles in functional metabolic pathways were also assessed. A total of 89 preterm infants born before 32 weeks gestation and 50 infants born at term age (above 37 completed weeks’ gestation) served as controls and were enrolled into the study. There were 21 and 24 urinary metabolites identified to be significantly associated with GA and BPD severity, respectively (p < 0.05). Among them, N-phenylacetylglycine, hippurate, acetylsalicylate, gluconate, and indoxyl sulfate were five metabolites that were significantly higher, with the highest importance in both infants with GA < 28 weeks and those with moderate to severe BPD, whereas betaine and N,N-dimethylglycine were significantly lower (p < 0.05). Furthermore, ribose and a gluconate related pentose phosphate pathway were strongly associated with these infants (p < 0.01). In conclusion, urinary metabolomic analysis highlights the crucial role of gut microbiota dysbiosis in the pathogenesis of BPD in preterm infants, accompanied by metabolites related to diminished antioxidative capacity, prompting an aggressive antioxidation response in extremely preterm infants with severe BPD.
AB - Bronchopulmonary dysplasia (BPD) is a chronic lung disease mainly affecting premature infants needing ventilation or oxygen for respiratory distress. This study aimed to evaluate the molecular linkages for BPD in very and extremely preterm infants using a metabolomics-based approach. A case-control study of enrolling preterm infants born before 32 weeks gestational age (GA) was prospectively performed. These preterm infants were subsequently stratified into the following two groups for further analysis: no or mild BPD, and moderate or severe BPD based on the 2019 NICHD criteria. Urinary metabolomic profiling was performed using 1H-Nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA) at a corrected age of 6 months. Metabolites significantly differentially related to GA and BPD severity were performed between groups, and their roles in functional metabolic pathways were also assessed. A total of 89 preterm infants born before 32 weeks gestation and 50 infants born at term age (above 37 completed weeks’ gestation) served as controls and were enrolled into the study. There were 21 and 24 urinary metabolites identified to be significantly associated with GA and BPD severity, respectively (p < 0.05). Among them, N-phenylacetylglycine, hippurate, acetylsalicylate, gluconate, and indoxyl sulfate were five metabolites that were significantly higher, with the highest importance in both infants with GA < 28 weeks and those with moderate to severe BPD, whereas betaine and N,N-dimethylglycine were significantly lower (p < 0.05). Furthermore, ribose and a gluconate related pentose phosphate pathway were strongly associated with these infants (p < 0.01). In conclusion, urinary metabolomic analysis highlights the crucial role of gut microbiota dysbiosis in the pathogenesis of BPD in preterm infants, accompanied by metabolites related to diminished antioxidative capacity, prompting an aggressive antioxidation response in extremely preterm infants with severe BPD.
KW - antioxidative capacity
KW - bronchopulmonary dysplasia
KW - gut microbiota
KW - urinary metabolomics
KW - very preterm infants
UR - http://www.scopus.com/inward/record.url?scp=85191293713&partnerID=8YFLogxK
U2 - 10.3390/metabo14040219
DO - 10.3390/metabo14040219
M3 - 文章
C2 - 38668347
AN - SCOPUS:85191293713
SN - 2218-1989
VL - 14
JO - Metabolites
JF - Metabolites
IS - 4
M1 - 219
ER -