Table 2.

Metabolites within pathways of interest identified as significant in more than one study.

Metabolite/Metabolite Derivatives	Pathway of Interest	Biospecimen	Method	Age Group	Atopic Focus	Outcome
Tyrosine	Tyrosine metabolism	Urine [15,24,38]	GC-MS [15] NMR [24,38]	6–11 years old [15] 4–16 years old [24] 3–5 years old [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 [15] 5–12 years old [22] Unborn, follow up at age 1 year [34]	Wheeze [34]/Asthma [15,22]	↓ 3-hydroxyphenylacetic acid in asthma vs. in HC [15] ↑ in infants without wheezing in their first year compared to wheezing infants [34] ↑ Hydroxyphenyllactic acid in uncontrolled asthma vs. HC [15] Negative correlation with forced expired volume in the first second (FEV1) and forced vital capacity (FVC) [22]
N-acetyltyrosine	Tyrosine metabolism	Urine [18,38]	NMR [18,38]	1–4 years old [18] 3–5 years old [38]	Asthma [18] Food allergy [38]	↓ in children at age 1 who develop asthma before age 4 vs. HC [18] ↑ in food sensitization (egg or milk) vs. no food sensitization [38]
Tryptophan	Tryptophan metabolism	Urine [15,24] Serum [37]	GC-MS [15] NMR [24] LC-MS [37]	6–11 years old [15] 4–16 years old [24] 3 months-3 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 [19] Serum [37]	LC-MS [19,37]	2–5 years old [19] 3 months-3 years old [37]	Wheeze/asthma [19] Atopic dermatitis [37]	↑ Transient wheezing vs. early-onset asthma [19] ↑ in AD with high IgE vs. HC and vs. AD with normal IgE level [37]
5-hydroxyindoleacetic acid/ 5-hydroxyindoleacetate (5-HIAA)	Tryptophan metabolism	Urine [15,22,23] Serum [16,23]	GC-MS [15,22] NMR [23] UPLC-MS [16]	5–12 years old [22] 6–11 years old [15] 1–12 years old [16,23]	Asthma [22,23] Food allergy [16]	↑ with a combination treatment of budesonide and salbutamol during acute asthma exacerbation [23] Distinguish HC from uncontrolled asthma and controlled asthma [15] Positive correlation with FEV1/FVC and negative correlation with exhaled nitric oxide (eNO) [22] Distinguish asthma vs. food allergy [16]
butyrate [17] 4-hydroxybutyrate [17] 4-hydroxybutyric acid [15] 3-hydroxybutyrate [23] 3-hydroxybutyric acid [15] 3-hydroxyisobutyric [23] 2-hydroxyisobutyrate [24] 2-hydroxybutyrate [36]	SCFAs (Microbial derivatives)	Stool [17] Urine [15,24,36] Serum [23]	NMR [23,24,36] GC-MS [15]	4–7 years old [17] 4–16 years old [24] 6–11 years old [15] 6–10 months old [36] 1–12 years old [23]	Asthma [15,17,23,24] Atopic dermatitis [36]	↑ 4-hydroxybutyrate in asthma vs. HC and ↓ butyrate in asthma vs. HC [17] Distinguish stable asthma from HC [24] ↑ AD vs. HC [36] ↑ 3-hydroxybutyric acid in uncontrolled vs. controlled asthma, but ↓ in asthmatics vs. HC [15] ↓ 4-hydroxybutyric acid. controlled and uncontrolled asthma vs. HC [15] ↑ with a combination treatment of budesonide and salbutamol during acute asthma exacerbation [23]
p-Cresol sulfate [26,31] p-Cresol [19] p-Cresol glucuronide [34]	Microbial derivatives (through tyrosine metabolism)	Stool [31] Urine [19] Plasma [26] Amniotic fluid [34]	MS [31] LC-MS [19] UPLC and GC-MS LC-MS and LC-MSE [34]	3 years old [31] 2–5 years old [19] 6–10 years [26] Unborn, follow up at age 1 year [34]	Wheeze/asthma [19,26,31,34]	Inversely associated with asthma [31], ↑ in the “transient wheezing” vs. ”early-onset” asthma [19] associated with wheezing during the first year of life vs. controls without wheezing episodes [34] current asthma was associated with a reduced level of p-Cresol sulfate vs. HC. This association was replicated in the validation group [26]
Taurocholate/Taurocholic acid (TCA) [16,26,37]	Bile acids	Plasma [26] Serum [16,37]	UPLC-MS and GC-MS [26] UPLC-MS [16] LC-MS [37]	6–10 years old [26] 1–12 years old [16] 3 months-3 years old [37]	Asthma [16,26] Atopic dermatitis [37]	↑ associated with current asthma [26] Distinguish asthma from non-atopic controls [16] Distinguish food allergy from asthma after adjustment for AD [16] ↓ AD independently of high or normal IgE level vs. HC [37]
Taurochenodeoxycholate/ Taurochenodeoxycholic acid (TCDCA) [16,37] Taurochenodeoxycholate-3-sulfate [30]	Bile acids	Serum [16,37] Urine [30]	UPLC-MS [16,30] LC-MS [37]	1–12 years old [16] 3 months-3 years old [37] 4 weeks-7 years old [30]	Wheeze [30]/Asthma [16,30] Atopic dermatitis [37]	Distinguish asthma from non-atopic controls [16] ↓ AD independently of high or normal IgE level vs. HC [37] ↑ in children who developed persistent wheeze/asthma [30]
Glycohyocholate/Glycohyocholic acid (GHCA)	Bile acids	Serum [16] Urine [35]	UPLC-MS [16] UPLC-MS and GC-MS [35]	1–12 years old [16] 3–12 months old [35]	Asthma [16] Wheeze and atopy [35] Food allergy [16]	Distinguish food allergy from asthma after adjustment for AD [16] ↑ in those children who developed atopy and wheeze at age one year compared to controls [35]
Glycocholate/glycocholic acid (GCA)	Bile acids	Serum [16,37]	UPLC-MS [16] LC-MS [37]	1–12 years old [16] 3 months-3 years old [37]	Asthma [16] Atopic dermatitis [37]	Distinguish asthma from non-atopic controls [16] ↓ AD independently of high or normal IgE level vs. HC [37]
Docosapentaenoate n-6	PUFAs	Stool [31] Serum [16]	MS [31] UPLC-MS [16]	3 years old [31] 1–12 years old [16]	Asthma [16,31] Food allergy [16]	Inversely associated with asthma [31] Distinguish food allergy from asthma after adjustment for AD [16]

Abbreviations: MS: mass spectrometry; LC: liquid chromatography; GC: gas chromatography; NMR: nuclear magnetic resonance; UPLC: Ultra performance liquid chromatography; HC: healthy controls; AD: atopic dermatitis; IgE: immunoglobulin E; FEV1: Forced Expired Volume in the first second; FVC: Forced Vital Capacity.