Table 4 Metabolite correlations
| Â | Primary outcome measure | Â | |||
|---|---|---|---|---|---|
Metabolite | ABC Corr. p value | SRS Corr. p value | Metabolic pathway | ||
Amino acids (endogenous) | |||||
 Arginine | 0.63 | 0.03 |  |  | Amino acid |
 Assymetric dimethylarginine (ADMA) |  |  | − 0.61 | 0.06 | Arginine catabolite (endogenous inhibitor of nitric oxide synthases) |
 N-delta-acetylornithine |  |  | 0.62 | 0.06 | Arginine catabolite |
 N-acetylputrescine |  |  | − 0.65 | 0.04 | Arginine catabolite |
 4-Acetamidobutanoate |  |  | − 0.62 | 0.06 | Arginine catabolite |
 Tryptophan | − 0.67 | 0.02 |  |  | Amino acid |
 Tyrosine | − 0.67 | 0.02 |  |  | Amino acid |
 Theanine |  |  | 0.7 | 0.02 | a.a. deriv. from tea—of food origin |
 Carnosine |  |  | 0.6 | 0.07 | a.a. deriv.; dietary; antioxidant; CNS functionality |
 β-hydroxyisovalerate | − 0.73 | 0.007 |  |  | a.a. metabolism (leucine) |
 α-hydroxyisocaproate | − 0.66 | 0.02 |  |  | a.a. metabolite (leucine) |
 4-Methyl-2-oxopentanoate |  |  | − 0.62 | 0.06 | a.a. metabolite (leucine) |
 α-hydroxyisovalerate | − 0.6 | 0.04 |  |  | a.a. metabolism (isoleucine) |
 2-Methylbutyrylcarnitine (C5) |  |  | 0.6 | 0.07 | a.a. derived (isoleucine) |
 3-Hydroxyisobutyrate |  |  | − 0.72 | 0.02 | a.a. metabolism (valine) |
 N-carbamoylalanine | 0.73 | 0.01 |  |  | a.a. metabolite (alanine) |
 N-methyltaurine |  |  | − 0.63 | 0.05 | a.a. metabolite (cysteine) |
 Taurine | − 0.6 | 0.04 |  |  | a.a. metabolite (cysteine); critical for oxidative stress |
 Dimethylglycine |  |  | − 0.61 | 0.06 | a.a. metabolite (glycine) |
 1-Methylguanidine |  |  | 0.7 | 0.02 | a.a. metabolism |
 N-acetylhistamine | 0.69 | 0.01 |  |  | a.a. metabolite (histidine) |
Amino acids (microbiome-associated or contributed) | |||||
 Tyramine O-sulfate | 0.61 | 0.03 |  |  | a.a. metabolite (tyrosine); catecholamine trigger |
 3-Indoxyl sulfate | 0.63 | 0.03 |  |  | a.a. metabolite (tryptophan); likely of gut microbiome origin |
 2-Oxindole-3-acetate |  |  | 0.61 | 0.06 | a.a. metabolite (tryptophan); likely of gut microbiome origin |
 Indolin-2-one | 0.61 | 0.03 |  |  | a.a. metabolite (tryptophan); likely of gut microbiome origin |
 Phenyllactate (PLA) |  |  | − 0.61 | 0.06 | a.a. metabolite (phenylalanine), contribution from gut microbiome |
 Phenylacetylglutamine | 0.65 | 0.02 |  |  | a.a. metabolite (glutamine); likely of gut microbiome origin |
 Tryptophan betaine |  |  | − 0.69 | 0.03 | a.a. (contribution from microbiome) |
 N-acetyl-cadaverine | 0.65 | 0.02 |  |  | a.a. degradation product (lysine); likely of gut microbiome origin |
Benzene metabolism | |||||
 Hydroquinone sulfate |  |  | − 0.66 | 0.04 | Benzene metabolite; likely of exogenous origin |
Caffeic acid derivatives | |||||
 Chlorogenate |  |  | 0.61 | 0.06 | Caffeic acid deriv.; dietary/food additive |
Cholesterol metabolism | |||||
 Cholesterol | − 0.75 | 0.005 |  |  | Cholesterol |
 Cholate |  |  | − 0.73 | 0.02 | Cholesterol (bile acid) |
 12-Dehydrocholate |  |  | − 0.69 | 0.03 | Cholesterol (bile acid), microbiome origin |
 7-Ketodeoxycholate |  |  | − 0.6 | 0.07 | Cholesterol (bile acid), microbiome origin |
 Glycocholenate sulfate | − 0.86 | < 0.001 |  |  | Cholesterol (bile acid), microbiome origin |
 Cortisone | − 0.8 | 0.002 |  |  | Cholesterol (hormone) |
 Cortisol 21-glucuronide | − 0.73 | 0.008 |  |  | Cholesterol (hormone) |
 Epiandrosterone glucuronide | − 0.68 | 0.01 |  |  | Cholesterol (hormone) |
 17α-hydroxypregnanolone glucuronide | − 0.61 | 0.03 |  |  | Cholesterol (hormone) |
 5α-androstan-3β,17α-diol disulfate | − 0.61 | 0.04 |  |  | Cholesterol (hormone) |
 Pregnen-diol disulfate |  |  | − 0.82 | 0.004 | Cholesterol (hormone) |
 Dehydroepiandrosterone glucuronide |  |  | − 0.78 | 0.008 | Cholesterol (hormone) |
 11-Ketoetiocholanolone sulfate |  |  | − 0.76 | 0.01 | Cholesterol (hormone) |
 5α-pregnan-3β,20α-diol disulfate |  |  | − 0.69 | 0.03 | Cholesterol (hormone) |
 5α-pregnan-3(α/β),20β-diol disulfate |  |  | − 0.68 | 0.03 | Cholesterol (hormone) |
 21-Hydroxypregnenolone disulfate |  |  | − 0.65 | 0.04 | Cholesterol (hormone) |
 3α,21-dihydroxy-5β-pregnane-11,20-dione 21-glucuronide |  |  | − 0.61 | 0.06 | Cholesterol (hormone) |
 Androstenediol 3β 17β d0 |  |  | − 0.6 | 0.07 | Cholesterol (hormone) |
Fatty acids | |||||
 Diglycerol | 0.66 | 0.02 |  |  | Lipid, likely of exogenous origin |
 Pimelate (heptanedioate) | 0.61 | 0.03 | 0.61 | 0.06 | Dicarboxylate fatty acid (DFA) |
 Suberate (octanedioate) |  |  | 0.75 | 0.01 | Dicarboxylate fatty acid (DFA) |
 Azeloylcarnitine (C9-DC) | 0.66 | 0.02 |  |  | Acylcarnitine-conjugated DFA |
Microbial polycyclic aromatic hydrocarbon (PAH) degradation | |||||
 Gentisate (2,5-diOH-benzoate) |  |  | 0.69 | 0.03 | Key intermediate in microbial PAH degradation |
 4-Hydroxybenzoate | − 0.63 | 0.03 |  |  | Gut microbiome/amino acid |
 3-Ethylphenylsulfate | − 0.63 | 0.03 |  |  | Gut microbiome/amino acid |
Monoterpene phenol | |||||
 Thymol sulfate | 0.62 | 0.03 |  |  | Monoterpene phenol of food origin |
Neurotransmitters | |||||
 N-methylglutamate |  |  | 0.65 | 0.04 | Neurotransmitter |
 Glutamine | − 0.77 | 0.003 |  |  | Neurotransmitter |
 Homovanillate (HVA) | − 0.62 | 0.03 | − 0.65 | 0.04 | Neurotransmitter |
 Hypoxanthine | − 0.62 | 0.03 | − 0.64 | 0.05 | Neurotransmitter |
 Serotonin | −0.61 | 0.03 |  |  | Neurotransmitter |
Oxidative stress | |||||
 γ-glutamylglutamine | − 0.63 | 0.03 |  |  | Oxidative stress |
 Methionine sulfone | − 0.62 | 0.03 |  |  | Oxidative stress |
Polyol | |||||
 3-Carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) |  |  | − 0.78 | 0.008 | Polyol associated with uremia |
Sphingomyelin | |||||
 Palmitoyl sphingomyelin (d18:1/16:0) | − 0.69 | 0.01 |  |  | Sphingomyelin |
 Stearoyl sphingomyelin (d18:1/18:0) | − 0.77 | 0.004 |  |  | Sphingomyelin |
 Lignoceroyl sphingomyelin (d18:1/24:0) | − 0.74 | 0.006 |  |  | Sphingomyelin |
 Behenoyl sphingomyelin (d18:1/22:0) | − 0.74 | 0.006 |  |  | Sphingomyelin |
 Sphingomyelin (d18:1/20:1, d18:2/20:0) | − 0.76 | 0.004 |  |  | Sphingomyelin |
 Sphingomyelin (d18:1/14:0, d16:1/16:0) | − 0.75 | 0.005 |  |  | Sphingomyelin |
 Sphingomyelin (d18:1/20:0, d16:1/22:0) | − 0.74 | 0.006 |  |  | Sphingomyelin |
Sugars | |||||
 Arabinose |  |  | − 0.7 | 0.02 | Sugar frequently associated with intestinal Candida overgrowth |
TCA cycle | |||||
 Malate | − 0.65 | 0.02 |  |  | TCA cycle intermediate |
Other | |||||
 Gentisic acid-5-glucoside |  |  | 0.65 | 0.04 | Xenobiotic (chemical) |
 Erythritol |  |  | − 0.83 | 0.003 | Xenobiotic (diet-derived) |
 1-Palmitoyl-2-oleoyl-GPE (16:0/18:1) | − 0.72 | 0.008 |  |  | Phospholipid |