Table 2.
Metabolites that most significantly differentiated GCS opium users from controls.
| Ontology level (OL) | Compound name (OL1, OL2a) | VIP | p-value* | Fold Change** |
|---|---|---|---|---|
| OL1 | Codeine | 2.7 | 7.24E-40 | 22.6 |
| OL1 | Codeine | 2.5 | 3.12E-35 | 42.9 |
| OL1 | Codeine-6-beta-D-glucuronide | 2.6 | 6.32E-35 | 25.5 |
| OL1 | Morphine | 2.3 | 2.62E-28 | 47.0 |
| OL1 | Morphine-3-beta-D-glucuronide | 2.3 | 1.54E-27 | 117.4 |
| OL1 | Ferulate | 2.1 | 4.18E-27 | 5.6 |
| OL1 | Morphine-6-beta-D-glucuronide | 2.3 | 1.58E-25 | 139.1 |
| OL1 | N-Acetyl-S-(2-carbamoylethyl)-L-cysteine | 2.0 | 4.16E-21 | 3.2 |
| OL1 | Pyridoxine | 1.9 | 1.44E-16 | 1.8 |
| OL1 | Hydroxycotinine | 1.7 | 6.88E-15 | 5.3 |
| OL1 | Cotinine | 1.6 | 1.34E-10 | 3.8 |
| OL1 | Allothreonine | 1.4 | 1.38E-09 | 1.4 |
| OL1 | Nicotine-N-oxide | 1.4 | 2.93E-09 | 3.7 |
| OL1 | Nicotine | 1.4 | 2.52E-08 | 4.5 |
| OL1 | Caffeic acid | 1.0 | 2.02E-07 | 4.8 |
| OL1 | Phenethylamine | 1.1 | 2.87E-07 | 1.6 |
| OL1 | Pantothenate | 1.9 | 5.07E-07 | −1.4 |
| OL1 | N-acetylcysteine | 1.5 | 9.07E-07 | 1.4 |
| OL1 | N-Acetyl-S- (3-hydroxypropyl)-L-cysteine | 1.5 | 1.07E-06 | 2.3 |
| OL1 | L-Tryptophan | 1.5 | 2.08E-06 | −1.4 |
| OL1 | Homovanillic acid | 1.6 | 4.32E-06 | −1.3 |
| OL1 | L-Tyrosine | 1.4 | 9.11E-06 | −1.4 |
| OL1 | DL-Leucine | 1.7 | 1.15E-05 | −1.6 |
| OL1 | 3,5 dihydroxybenzyl alcohol | 1.4 | 5.64E-05 | −1.5 |
| OL1 | N-Methyl-L-glutamic acid | 1.6 | 5.83E-05 | −1.5 |
| OL1 | L-Isoleucine | 1.4 | 1.09E-04 | −1.4 |
| OL1 | N-Acetyl-DL-tryptophan | 1.6 | 1.19E-04 | −1.6 |
| OL1 | N-acetylglutamate | 1.4 | 1.75E-04 | −1.2 |
| OL1 | 1-Methyl-L-histidine | 0.8 | 1.01E-03 | 1.3 |
| OL1 | N-acetylasparagine | 1.2 | 1.12E-03 | −1.3 |
| OL1 | N-Acetyl-S- (3,4-dihydroxybutyl)-L-cysteine | 1.3 | 1.36E-03 | 1.3 |
| OL1 | Biotin | 1.2 | 3.60E-03 | −1.5 |
| OL1 | Mevalonate | 1.0 | 4.05E-03 | −1.3 |
| OL1 | p-Methylhippuric acid | 0.7 | 5.75E-03 | 1.7 |
| OL1 | 10-hydroxydecanoic acid | 1.1 | 6.11E-03 | −1.3 |
| OL1 | Glucuronate | 0.9 | 7.38E-03 | 1.3 |
| OL1 | L-carnitine | 0.9 | 7.70E-03 | −1.5 |
| OL1 | Pipecolate | 1.1 | 8.81E-03 | −1.8 |
| OL1 | N-acetylleucine | 0.9 | 9.84E-03 | −1.3 |
| OL1 | N,n-dimethyl-arginine | 1.1 | 1.15E-02 | 1.1 |
| OL1 | Cytidine | 1.3 | 1.26E-02 | −1.1 |
| OL1 | Creatine | 0.9 | 1.35E-02 | −1.8 |
| OL1 | S-adenosylhomocysteine | 1.2 | 1.60E-02 | 1.2 |
| OL1 | 4-hydroxy-3-methoxyphenylglycol | 1.1 | 1.83E-02 | −1.4 |
| OL1 | Azelate | 0.9 | 2.02E-02 | −1.4 |
| OL1 | Anthranilate | 0.8 | 2.11E-02 | −1.5 |
| OL1 | Succinic acid | 1.1 | 2.24E-02 | −1.2 |
| OL1 | O-acetylcarnitine | 0.9 | 2.82E-02 | −1.7 |
| OL1 | N-acetylleucine | 0.8 | 2.87E-02 | −1.1 |
| OL1 | 4-Hydroxyhippuric acid | 0.7 | 2.87E-02 | 1.3 |
| OL1 | L-Methionine | 1.0 | 3.06E-02 | −1.2 |
| OL1 | 2-aminophenol | 0.7 | 3.19E-02 | 1.2 |
| OL1 | Suberate | 0.9 | 3.30E-02 | −1.3 |
| OL1 | 3,4-Dihydroxybenzaldehyde | 0.7 | 3.47E-02 | 1.3 |
| OL1 | Pyroglutamic acid | 1.1 | 3.50E-02 | −1.1 |
| OL1 | 4-Pyridoxic acid | 1.0 | 3.80E-02 | −1.1 |
| OL1 | Raffinose | 0.6 | 4.05E-02 | −1.4 |
| OL1 | 3-Hydroxy-3-methylglutaric acid | 1.0 | 4.64E-02 | −1.2 |
| OL1 | Cortisol | 0.5 | 5.11E-02 | 1.3 |
| OL1 | Xanthurenate | 0.9 | 5.78E-02 | −1.1 |
| OL1 | N-Acetyl-D-galactosamine | 1.0 | 6.48E-02 | 1.1 |
| OL1 | 10-hydroxydecanoic acid | 0.6 | 6.53E-02 | −1.3 |
| OL1 | Trigonelline | 0.6 | 6.68E-02 | −1.2 |
| OL1 | Tryptamine | 0.8 | 7.25E-02 | −1.1 |
| OL1 | Betaine | 0.7 | 7.42E-02 | −1.3 |
| OL1 | Adenine | 0.8 | 7.60E-02 | −1.5 |
| OL1 | 2,6-Diaminopimelic acid | 0.5 | 8.23E-02 | 1.3 |
| OL1 | Adenosine | 1.0 | 8.37E-02 | 1.1 |
| OL1 | N-methyltryptamine | 0.6 | 8.50E-02 | −1.4 |
| OL1 | N-acetylserine | 0.7 | 9.36E-02 | 1.1 |
| OL1 | Hippuric acid | 0.6 | 9.52E-02 | −1.1 |
| OL2A | DL-2-Aminoadipic acid | 2.0 | 1.55E-26 | 3.8 |
| OL2A | Codeine | 2.2 | 1.23E-24 | 24.9 |
| OL2A | 5'-deoxyadenosine | 2.1 | 3.29E-24 | 13.6 |
| OL2A | Mono benzyl phthalate | 1.7 | 1.50E-19 | |
| OL2A | Indoleacetaldehyde | 1.8 | 5.48E-19 | 3.5 |
| OL2A | 1-Aminocyclopropanecarboxylic acid | 1.5 | 1.17E-12 | 1.5 |
| OL2A | Indole-3-ethanol | 2.0 | 8.64E-12 | 2.2 |
| OL2A | 4-Hydroxyhippuric acid | 1.3 | 1.24E-11 | 8.2 |
| OL2A | 3-methoxytyramine | 1.8 | 2.56E-11 | 1.5 |
| OL2A | N-acetylputrescine | 1.7 | 3.31E-10 | 1.3 |
| OL2A | 5-aminolevulinate | 1.7 | 1.04E-09 | 1.8 |
| OL2A | N-acetylalanine | 1.6 | 6.33E-09 | 1.7 |
| OL2A | Pyridoxal | 1.4 | 1.12E-08 | 1.6 |
| OL2A | Monoisopropyl phthalate | 1.1 | 3.90E-08 | 16.2 |
| OL2A | 3-methylhistamine | 1.2 | 8.37E-07 | 1.3 |
| OL2A | Guanidineacetic acid | 1.7 | 1.24E-06 | −1.6 |
| OL2A | Itaconate | 1.4 | 2.48E-06 | 2.3 |
| OL2A | N-Acetyl-S- (3,4-dihydroxybutyl)-L-cysteine | 1.4 | 5.43E-06 | 1.4 |
| OL2A | 5-Methylcytosine hydrochloride | 1.6 | 9.50E-06 | −1.7 |
| OL2A | 3,4,5-trimethoxybenzaldehyde | 0.8 | 1.20E-05 | 2.7 |
| OL2A | Taurine | 1.2 | 3.81E-05 | 1.6 |
| OL2A | N-acetylphenylalanine | 1.6 | 1.55E-04 | −1.9 |
| OL2A | Mono (2-ethyl-5-hydroxyhexyl) phthalate | 1.6 | 1.06E-03 | −1.9 |
| OL2A | L-Proline | 1.1 | 1.51E-03 | 1.8 |
| OL2A | Deoxyadenosine | 1.2 | 2.60E-03 | −1.2 |
| OL2A | Homoveratric acid | 1.1 | 2.86E-03 | −1.2 |
| OL2A | Threonine | 0.9 | 3.45E-03 | −1.5 |
| OL2A | 3-(carbamoylamino)propanoic acid | 1.3 | 3.75E-03 | −1.3 |
| OL2A | 6-carboxyhexanoate | 1.0 | 3.88E-03 | −1.3 |
| OL2A | Methyglutarate | 1.1 | 4.34E-03 | −1.2 |
| OL2A | Anserine | 0.9 | 5.25E-03 | −2.1 |
| OL2A | 4-acetamidobutanoic acid | 1.3 | 5.42E-03 | −1.1 |
| OL2A | Nicotinamide | 0.5 | 6.91E-03 | 1.7 |
| OL2A | Aniline-2-sulfonate | 1.1 | 8.76E-03 | −1.4 |
| OL2A | Methyl galactoside | 1.2 | 1.36E-02 | −2.3 |
| OL2A | Kynurenine | 0.9 | 1.38E-02 | −1.3 |
| OL2A | 1-methyladenosine | 1.0 | 1.98E-02 | −1.5 |
| OL2A | N-acetyl-S- (3,4-dihydroxybutyl)-L-cysteine | 0.5 | 2.39E-02 | 3.1 |
| OL2A | N-acetylphenylalanine | 0.7 | 2.40E-02 | 1.6 |
| OL2A | 3,4,5-trimethoxybenzaldehyde | 0.9 | 2.40E-02 | −1.6 |
| OL2A | Cytidine | 0.7 | 2.89E-02 | 1.2 |
| OL2A | 5-hydroxytryptophan | 1.2 | 2.91E-02 | −1.2 |
| OL2A | N-acetylalanine | 1.0 | 2.92E-02 | −1.1 |
| OL2A | N-acetylproline | 1.0 | 3.05E-02 | −1.2 |
| OL2A | Uridine | 0.9 | 3.48E-02 | −1.2 |
| OL2A | Creatinine | 1.2 | 3.84E-02 | −1.1 |
| OL2A | Hydrocinnamic acid | 0.5 | 4.85E-02 | 1.9 |
| OL2A | O-acetylcarnitine | 0.7 | 4.86E-02 | 1.2 |
| OL2A | Monoethyl phthalate | 1.0 | 4.92E-02 | −1.2 |
| OL2A | Mannose | 0.9 | 5.09E-02 | −4.1 |
| OL2A | Homoveratric acid | 0.8 | 7.97E-02 | −1.4 |
| OL2A | Estradiol-17alpha | 0.5 | 8.07E-02 | 1.4 |
| OL2A | Sebacate | 1.0 | 9.00E-02 | −1.2 |
| OL2A | 6-hydroxypyridine-3-carboxylic acid | 1.0 | 9.38E-02 | −1.2 |
Additional metabolites that met the criteria of VIP ≥1, p < 0.10, or foldchange ≥2 are reported in Supplementary Tables.
*
t-test with Satterthwaite correction for unequal variances.
**
Positive fold change - mean Opium User > mean Non-Opium User.