Metabolomic Analysis Reveals Distinct Profiles in the Plasma and Urine Associated with IgE Reactions in Childhood Asthma

Abstract

Several metabolomics studies have identified altered metabolic pathways that are related to asthma. However, an integrative analysis of the metabolic responses across blood and urine for a comprehensive framework of asthma in early childhood remains lacking. Fifty-four age-matched children with asthma (n = 28) and healthy controls (n = 26) were enrolled. Metabolome analysis of the plasma and urine samples was performed using 1H-nuclear magnetic resonance (NMR) spectroscopy coupled with partial least-squares discriminant analysis (PLS-DA). Integrated analysis of blood and urine metabolic profiling related to IgE reactions for childhood asthma was investigated. A significantly higher plasma histidine level was found, in parallel with lower urinary 1-methylnicotinamide and trimethylamine N-oxide (TMAO) levels, in children with asthma compared to healthy controls. Compared to children without allergic sensitization, 11 (92%) plasma metabolites and 8 (80%) urinary metabolites were found to be significantly different in children with IgE and food sensitization respectively. There were significant correlations between the plasma 3-hydroxybutyric acid and excreted volumes of the hydroxy acids, which were strongly correlated to plasma leucine and valine levels. Urine N-phenylacetylglycine, a microbial-host co-metabolite, was strongly correlated with total serum and food allergen-specific IgE levels. Plasma pyruvate and urine valine, leucine, and isoleucine degradation metabolisms were significantly associated with allergic sensitization for childhood asthma. In conclusion, blood and urine metabolome reflect different metabolic pathways in allergic reactions. Plasma pyruvate metabolism to acetic acid appears to be associated with serum IgE production, whereas urine branched-chain amino acid metabolism primarily reflects food allergic reactions against allergies.

The Metabolomics of Childhood Atopic Diseases: A Comprehensive Pathway-Specific Review

“…Characteristics of the included studies are presented in the Supplementary Materials (Table S1) . Asthma was examined in 19 studies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], wheeze in six [ 14 , 19 , 32 , 33 , 34 , 35 ], AD in two [ 36 , 37 ], and allergy (allergic rhinitis or food allergy) in five studies [ 16 , 17 , 18 , 35 , 38 ]. The number of atopic children with either asthma, wheeze, allergy, or AD ranged from 20 [ 14 , 36 ] to 380 [ 27 ].…”

“…Pathway analysis demonstrated that 5 of these variables are part of 2 pathways: steroid hormone biosynthesis (p = 0.003) and 2-phenylalanine metabolism (p = 0.009) emerging as probably perturbed pathways. [38] Asthma [15,24] Food allergy [38] ↑ in uncontrolled asthma vs. healthy controls (HC) [15] ↑ in uncontrolled asthma vs. controlled asthma [15] Distinguish unstable asthma from stable asthma [24] Distinguish stable asthma from HC [24] ↑ in food sensitization (egg or milk) vs. no food sensitization [38] 3-hydroxyphenylacetic acid [15,34] Hydroxyphenyllactic acid [15] 4-hydroxyphenylacetic [22] Tyrosine metabolism Urine [15,22] Amniotic fluid [34] GC-MS [15,22] LC-MS and LC-MSE [34] 6-11 years old [ [37] Asthma [15,24] Atopic dermatitis [37] ↑ in uncontrolled asthma vs. HC [15] Distinguish unstable from stable asthma and stable asthma from HC [24] ↑ in AD with high IgE vs. HC and vs. AD with normal IgE level [37] Indolelactic acid Tryptophan metabolism…”

“…Urine [15,18,20,22,24,38] Serum [16,29] Amniotic fluid [34] GC-MS [15,22] NMR [18,24,38] LC-MS [20,29] LC-MS and LC-MSE [34] UPLC-MS [16] Wheeze [34]/Asthma [15,18,20,22,24,29] Food allergy [16,38] Significant metabolite(s) within pathway associated with wheeze, asthma [15,18,20,22,24,29,34] or food allergy [16,38]. A statistically significant asthma pathway [15].…”

Alterations in Serum-Free Amino Acid Profiles in Childhood Asthma

“…Furthermore, there are not enough studies profiling metabolites in more than one biospecimen type, so it is not possible to determine the relationship between metabolites in different biological samples from the same person. Recently, Chiu et al [ 62 ] simultaneously analyzed the metabolic profile of blood and urine related to IgE reactions for childhood asthma. Their research showed a significantly higher level of histidine in plasma and a lower concentration of 1-methylnicotinamide and trimethylamine N-oxide (TMAO) in the urine of asthmatic children compared to healthy individuals.…”

“…Their research showed a significantly higher level of histidine in plasma and a lower concentration of 1-methylnicotinamide and trimethylamine N-oxide (TMAO) in the urine of asthmatic children compared to healthy individuals. Furthermore, Chiu et al [ 62 ] correlated the plasma level of 3-hydroxybutyric acid, leucine, and valine to the urine concentration of hydroxy acids. However, this was a single comparative study, and more advanced research using different biospecimens in parallel, like exhaled breath condensate, urine, plasma, and serum, is needed.…”