Table 3.

Pathways of interest associated with asthma, allergy, or atopic dermatitis in more than one study.

Pathway	Biospecimen	Method	Atopic Focus	Outcome
Tyrosine 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]. Pathway affected by corticosteroid resistance [20].
Tryptophan metabolism	Urine [15,19,23,24] Serum [16,23,29] Amniotic fluid [34]	GC-MS [15] NMR [23,24] LC-MS [19,29,37] UPLC-MS [16] LC-MS and LC-MSE [34]	Wheeze/Asthma [15,19,23,24,29,34] Atopic dermatitis [37] Food allergy [16]	Significant metabolite(s) within pathway associated with wheeze [34], asthma [15,19,22,24,29], food allergy [16], atopic dermatitis [37] or asthma treatment [23]
Microbial derivatives Including (SCFAs)	Plasma [26] Stool [17,31] Amniotic fluid [34] Urine [15,19] Serum [23]	UPLC-MS and GC-MS [26] MS [31] LC-MS and LC-MSE [34] LS-MS [19] NMR [17,23,24,36] LC-MS [19] GC-MS [15]	Wheeze/Asthma [15,17,19,23,24,26,31,34] Atopic dermatitis [36]	Significant metabolite(s) within pathway associated with wheeze [19,34], asthma [15,17,24,26,31], AD [36] or asthma treatment [23]
Bile acids	Urine [30,35] Plasma [26] Serum [16,23,37]	UPLC-MS and GC-MS [26,35] UPLC-MS [16,30] LC-MS [37] NMR [23]	Wheeze/asthma [16,23,26,30,35] Atopic dermatitis [37] Food allergy [16]	Significant metabolite(s) within pathway associated with wheeze [35], asthma [16,26,30], food allergy [16], AD [37] or asthma treatment [23]. Pathway analysis revealed that one of the most dysregulated pathways associated with the presence of FA in comparison with asthma included secondary bile acid metabolism [16].
PUFAs	Plasma [27] Stool [31] Serum [16,37]	LC-MS [27,37] MS [31] UPLC-MS [16]	Asthma [16,27,31] Food allergy [16] Atopic dermatitis [37]	Significant metabolite(s) within pathway associated with asthma [16,31], food allergy [16] or AD [37]. Linoleic acid metabolism was significantly enriched and associated with three phenotypic aspects of asthma defined by the degree of lung function: airway hyperresponsiveness to methacholine and FEV1/FVC ratio before and after the use of a bronchodilator [27]. Hydroxyl octadecadienoic acids (HODEs) and most hydroxy eicosatetraenoic acids (HETEs) increased in AD (with high and normal IgE level) vs. controls [37]. PUFA module (including 9 PUFAs) was inversely associated with asthma [16].
Lipids, sphingolipids, and ceramides	Plasma [25,27] Urine [19] Serum [16,37]	LC-MS [19,25,27,37] UPLS-MS [16]	Asthma [16,25,27] Atopic dermatitis [37] Food allergy [16]	Significant metabolite(s) within pathway associated with asthma [16,19], food allergy [16] or AD [37]. Baseline FEV1 was significantly correlated with glycerophospholipid-anchor biosynthesis [25]. Enrichment in the glycerophospholipid pathway was associated with airway hyperresponsiveness and FEV1/FVC ratio before and after using a bronchodilator [27]. The sphingolipid pathway was specific airway hyperresponsiveness to methacholine [27]. Pathway analysis showed that the pathways strongest associated with the presence of FA in comparison with control subjects included dihydrosphingomyelins, lactosylceramides, sphingomyelins, and hexosylceramides, among others [16].

Abbreviations: MS: mass spectrometry; LC: liquid chromatography; GC: gas chromatography; NMR: nuclear magnetic resonance; UPLC: Ultra performance liquid chromatography; AD: atopic dermatitis; FA: food allergy; FEV1: Forced Expired Volume in the first second; FVC: Forced Vital Capacity.