Chih-Yung Chiu1,2,3, Gigin Lin4, Mei-Ling Cheng5,6, Meng-Han Chiang2, Ming-Han Tsai1,2, Kuan-Wen Su1,2, Man-Chin Hua1,2, Sui-Ling Liao1,2, Shen-Hao Lai2,3, Tsung-Chieh Yao2,3, Kuo-Wei Yeh2,3, Jing-Long Huang2,3. 1. Department of Pediatrics, Chang Gung Memorial Hospital at Keelung, Chang Gung University, Taoyuan, Taiwan. 2. Community Medicine Research Centre, Chang Gung Memorial Hospital, Keelung, Taiwan. 3. Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan. 4. Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan. 5. Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 6. Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.
Abstract
BACKGROUND: Several metabolites and altered metabolic pathways have been reported to be associated with asthma. However, longitudinal analysis of the dynamics of metabolites contributing to the development of asthma has not yet been fully clarified. METHODS: We sought to identify the metabolic mechanisms underlying asthma development in early childhood. Thirty children with asthma and paired healthy controls from a prospective birth cohort were enrolled. Time series analysis of urinary metabolites collected at ages 1, 2, 3, and 4 years was assessed using 1 H nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA). Metabolites identified were studied in relation to changes over time in a linear mixed model for repeated measures. RESULTS: A total of 172 urine samples collected from the enrolled children were analyzed. Urinary metabolomics identified four metabolites significantly associated with childhood asthma development, with longitudinal analysis. Among them, dimethylamine, a metabolite produced by intestinal bacteria, appeared to shift from higher to lower level during asthma development. A persistent lower level of 1-methylnicotinamide and allantoin was found in children with asthma, with a peak difference at age 3 years (P = .032 and P = .021, respectively). Furthermore, a significant inverse correlation was found between allantoin and house dust mite sensitization (Spearman's r = -.297 P = .035). CONCLUSIONS: Longitudinal urinary metabolomic profiling provides a link of microbe-environment interactions in the development of childhood asthma. 1-Methylnicotinamide and allantoin may participate in allergic reactions in response to allergen exposure, potentially serving as specific biomarkers for asthma.
BACKGROUND: Several metabolites and altered metabolic pathways have been reported to be associated with asthma. However, longitudinal analysis of the dynamics of metabolites contributing to the development of asthma has not yet been fully clarified. METHODS: We sought to identify the metabolic mechanisms underlying asthma development in early childhood. Thirty children with asthma and paired healthy controls from a prospective birth cohort were enrolled. Time series analysis of urinary metabolites collected at ages 1, 2, 3, and 4 years was assessed using 1 H nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA). Metabolites identified were studied in relation to changes over time in a linear mixed model for repeated measures. RESULTS: A total of 172 urine samples collected from the enrolled children were analyzed. Urinary metabolomics identified four metabolites significantly associated with childhood asthma development, with longitudinal analysis. Among them, dimethylamine, a metabolite produced by intestinal bacteria, appeared to shift from higher to lower level during asthma development. A persistent lower level of 1-methylnicotinamide and allantoin was found in children with asthma, with a peak difference at age 3 years (P = .032 and P = .021, respectively). Furthermore, a significant inverse correlation was found between allantoin and house dust mite sensitization (Spearman's r = -.297 P = .035). CONCLUSIONS: Longitudinal urinary metabolomic profiling provides a link of microbe-environment interactions in the development of childhood asthma. 1-Methylnicotinamide and allantoin may participate in allergic reactions in response to allergen exposure, potentially serving as specific biomarkers for asthma.
Authors: Daniela Rago; Casper-Emil T Pedersen; Mengna Huang; Rachel S Kelly; Gözde Gürdeniz; Nicklas Brustad; Hanna Knihtilä; Kathleen A Lee-Sarwar; Andréanne Morin; Morten A Rasmussen; Jakob Stokholm; Klaus Bønnelykke; Augusto A Litonjua; Craig E Wheelock; Scott T Weiss; Jessica Lasky-Su; Hans Bisgaard; Bo L Chawes Journal: Am J Respir Crit Care Med Date: 2021-04-01 Impact factor: 21.405
Authors: Bo L Chawes; Giuseppe Giordano; Paola Pirillo; Daniela Rago; Morten A Rasmussen; Jakob Stokholm; Klaus Bønnelykke; Hans Bisgaard; Eugenio Baraldi Journal: Metabolites Date: 2019-09-16