Table 2.

Metabolomics-based targets of ASD.

Reference	Matrix	N of Subjects	Analytical Technique	Metabolite Implicated and Metabolic Process
[65] Graham et al., 2016	Brain	11 ASD and 11 controls	LC-LTQ Orbitrap MS	3-methoxytyramine, 5,6-dihydrouridine, N-carboxyethyl-γ-aminobutyric acid (dopamine, nucleotide metabolism and cell growth and proliferation)
[66] Kurochkin et al., 2019	Brain	32 ASD and 40 controls	UPLC–MS/MS	5-oxoproline, glutathione disulfide, Glutathione, l-γ-glutamyl-cysteine, l-cysteinyl-glycine (glutathione; purine; pyruvate; propanoate; TCA cycle; galactose; starch and sucrose; nicotinate and nicotinamide; cysteine and methionine; arginine and proline metabolism)
[67] Kuwabara et al., 2013	Blood	25 ASD and 28 controls	CE-TOF MS	arginine, taurine, 5-Oxoproline, lactic acid (oxidative stress and mitochondrial dysfunction)
[68] West et al., 2014	Blood	52 ASD and 30 controls	LC-MS and GC-MS	aspartate, DHEA-S, glutaric acid, serine, succinic acid citrate, creatinine, isoleucine, hydroxyphenyllactate, glutamate (energy production, mitochondrial disease or dysfunction and oxidative stress)
[69] Wang et al., 2016	Blood	173 ASD and 163 controls	UPLC/Q–TOF– MS/MS	decanoylcarnitine, pregnanetriol, adrenic acid, docosahexaenoic acid, sphingosine-1-phosphate, uric acid (β-oxidation, fatty acid and mitochondrial dysfunction)
[70] Rangel-Huerta et al., 2019	Blood	20 ASD and 30 controls	UPLC–MS/MS	1-methylnicotinamide, 3-Indoxyl sulfate, 4-methyl-2-oxopetane, 5-bromotryptophan, 6-hydroxyindole sulfate, cortisone, methionine, tryptophan, γ-glutamylmethionine, ursodeoxycholate, sphingomyelins, kynurenine, choline phosphate, decanoylcarnitine, 2-keto-3-deoxyglutamate, arachidate, behenate, fructose, sebacate, dodecanedioate, glutamate, aspartate, orotate, galactitol, N-acetyl-aspartyl glutamate (amino acid, lipid, nicotinamide)
[71] Kelly RS et al., 2019	Blood	403 children of which 52 ASD	UPLC-MS / MS	trimethylamine N-oxide, cinnamoylglycine, linoleoyl ethanolamide, palmitoyl ethanolamide, erythritol, docosahexaenoylcarnitine, prolylhydroxyproline, alpha-ketobutyrate, serotonin, oleoyl ethanolamide, N-formylphenylalanine, 5-Hydroxyindoleacetate, pyrraline, sphingomyelin, N-formylanthranilic acid (Endocannabinoid metabolism, Xenobiotics, Tryptophan metabolism, Urea cycle, Amino acid mebolism, Fatty acid metabolism, Phospholipid metabolism, Sphingolipid metabolism)
[72] Yap et al., 2010	Urine	39 ASD and 34 controls	1H-NMR	N-methylnicotinamide, N-methylnicotinic acid, dimethylamine, succinic acid, taurine, N-methyl-2-pyridone-5-carboxamide, hippurate, phenylacetylglutamine, platelet serotonin (gut microbiota and gastrointestinal dysfunction)
[73] Ming et al., 2012	Urine	48 ASD and 53 controls	UPLC–MS/MS and GC-MS	trans-Urocanate, glutaroylcarnitine, 3-methylglutaroylcarnitine, β-alanine, alanine, carnosine, glycine, histidine, serine, threonine, taurine, uric acid (oxidative stress; amino acid; mammalian microbial co-metabolism)
[74] Mavel et al., 2013	Urine	30 ASD and 28 controls	2D-NMR	serotonin, glycine, β-alanine, taurine, succinic acid, creatine, 3-methylhistidine (dopaminergic, serotonergic, synapse, tryptophan, oxidation, amino acids metabolism)
[75] Emond et al., 2013	Urine	26 ASD and 24 controls	GC-MS	succinic acid, glycolic acid, hippurate, phosphate, palmitate, stearate, 3-methyladipate (gut microbiota)
[76] Noto et al., 2014	Urine	21 ASD and 21 controls	GC-MS	3,4-dihydroxybutyric acid, glycolic acid, homovanillic acid, tryptophan 1,2,3-butanetriol, fructose, propylene glycol (interactions among diet, gut microbiota and host genetics)
[77] Diémé et al., 2015	Urine	30 ASD and 32 controls	1H-NMR, 2D-HSQC NMR, LC-HRMS	N-acetylarginine, indoxyl, indoxylsulfate, dihydroxy-1H-indole glucuronide, methylguanidine, desaminotyrosine, dihydrouracil (gut microbiota)
[78] Bitar et al., 2018	Urine	40 ASD and 40 controls	1H-NMR, 2D-HSQC NMR and LC-HRMS	5-amino-imidazole-4-carboxamide, chalice acid, glutamic acid, N-phosphoserine, nicotinamide ribonucleotide, glycerol-3-phosphate, trigonelline, riboflavin, 2-hydroxybutyric acid, 5-oxoproline, acetylcarnitine, cysteic acid, citric acid, threonine, creatine, serine, N-acetylphenylalanine;tyrosine, hydroxybenzoic acid, hydroxyproline, lactic acid, guanine, N-amidino aspartic acid, methyl acetoacetic acid, urocanic acid (amino acids; carbohydrates and oxidative stress)
[79] Barone et al., 2018	Dried Blood	83 ASD and 79 controls	ESI-Tandem MS/MS system	citrulline, acetylcarnitine, methylmalonyl/3-OH isovalerylcarnitine, decanoylcarnitine, dodecanoylcarnitine, tetradecadienoylcarnitine, hexadecanoylcarnitine, octadecenoylcarnitine (amino acids, fatty acid, gastrointestinal disturbances and mitochondrial dysfunction)