Table 3.
Abundance (106) of annotated metabolites that discriminated metabotypes of breast milk provided to preterm infants with “faster” or “slower” growth during the W2 to W4 lactation period.
| Abundance Des Ions (106) | ||||||
|---|---|---|---|---|---|---|
| Metabolites (Annotation Level) | a, b, c | mz | Median (25% and 75% Percentile), W2 to W4 | |||
| “Slower“ Growth (n = 38) | “Faster“ Growth (n = 29) | Mann-Whitney p-Value (FDR-Corrected MW q-Value in Exposant) | MLR p-Value (FDR-Corrected MLR q-Value in Exposant) | |||
| Amino acid | ||||||
| Hippuric acid 1 | a | 180.0654 (M + H)+ | 1.36 (0.79–1.81) | 1.36 (0.88–2.20) | 0.86 | 0.33 |
| 2-hydroxyhippuric acid 2 | a, b, c | 194.0459 (M – H)− | 0.07 (0.05–0.126) | 0.08 (0.05–0.15) | 0.25 | 0.04 |
| Valine 1 | a | 118.0865 (M + H)+ | 2.81 (1.72–3.23) | 2.67 (0.91–3.17) | 0.79 | 0.17 |
| Leucine 1 | a, c | 130.0872 (M – H)− | 1.92 (1.45–2.87) | 2.99 (1.61–4.66) | 0.02 ** | 0.92 |
| N-Carbamoylsarcosine 2 | a, c | 133.0609 (M + H)+ | 0.96 (0.66–1.45) | 1.69 (1.18–2.38) | 0.0003 ** | 0.96 |
| Tryptophan metabolism | ||||||
| Tryptophan 1 | a, c | 205.0970 (M + H)+ | 4.20 (3.59–4.77) | 4.76 (3.51–7.95) | 0.18 | 0.79 |
| Kynurenine 1 | a, c | 192.0653 (M–NH3 + H)+ | 0.97 (0.64–1.55) | 0.72 (0.59–0.93) | 0.06 t | 0.80 |
| 1H-Indole-3-carboxaldehyde 2 | a, b | 146.0599 (M + H)+ | 2.18 (1.55–2.81) | 2.26 (1.66–3.63) | 0.27 | 0.98 |
| Indole-3-ethanol 2 | a | 184.0732 (M + Na)+ | 9.66 (6.11–13.01) | 9.59 (6.62–12.06) | 0.82 | 0.14 |
| 3-Methylindole 2 | a | 132.0806 (M + H)+ | 0.43 (0.35–0.55) | 0.47 (0.39–0.63) | 0.10 | 0.70 |
| Tyrosine metabolism | ||||||
| hydroxyphenylacetic acid 1 | a, c | 151.0399 (M – H)− | 0.32 (0.25–0.37) | 0.30 (0.21–0.37) | 0.61 | 0.08 |
| p-Cresol (4-methylphenol) 2 | a, b, c | 107.0501 (M – H)− | 1.84 (1.16–2.85) | 1.37 (0.09–2.21) | 0.04 * | 0.20 |
| p-Cresol sulfate 2 | a | 187.0070 (M – H)− | 5.28 (4.14–9.27) | 4.89 (2.67–6.79) | 0.13 t | 0.17 |
| Sulphur metabolism | ||||||
| Cystathionine 2 | a | 240.1015 (M + NH4)+ | 0.67 (0.51–0.80) | 0.87 (0.66–1.35) | 0.02 * | 0.90 |
| Methionin 1 | a, c | 150.0580 (M + H)+ | 1.82 (1.49–2.19) | 1.81 (1.63–2.69) | 0.36 | 0.89 |
| Se-Adenosylselenohomocysteine 2 | a | 228.0314 (M + H + Na)+ | 0.22 (0.17–0.25) | 0.19 (0.13–0.24) | 0.15 t | 0.09 |
| S-Adenosylhomocysteine 2 | a | 365.1048 (M – H2O– H)+ | 6.53 (5.02–7.63) | 4.48 (3.92–6.84) | 0.007 * | 0.20 |
| Hydrogen sulfite 2 | a, b, c | 79.9573 (M – H)− | 0.52 (0.38–0.85) | 0.44 (0.31–0.67) | 0.07 t | 0.23 |
| Thiocyanic acid 2 | a, c | 150.0018 (M – H)− | 0.75 (0.64–0.83) | 0.57 (0.51–0.76) | 0.02 * | 0.69 |
| Aromatic compound | ||||||
| Benzoic acid 1 | a | 121.0294 (M – H)− | 3.14 (2.27–4.18) | 2.49 (2.09–2.95) | 0.01 * | 0.16 |
| Hydroxyphenyllactic acid 2 | a | 241.0730 (M + Hac-H)− | 0.14 (0.11–0.16) | 0.11 (0.08–0.18) | 0.17 | 0.96 |
| Pyridines and Derivatives/Nucleosides | ||||||
| Niacinamide 1 | a | 123.0554 (M + H)+ | 6.45 (5.27–10.82) | 11.00 (6.17–13.84) | 0.029 * | 0.16 |
| Energy metabolism | ||||||
| Hydroxyhexanoylcarnitine 2 | a | 276.1803 (M + H)+ | 0.11 (0.04–0.22) | 0.08 (0.05–0.21) | 0.84 | 0.52 |
| Oxoicosanoyl-CoA 2 | a, b | 547.2129 (M + H+ NH4)+ | 0.66 (0.53–0.89) | 0.81 (0.63–1.20) | 0.04 * | 0.87 |
| 3-Hydroxypimelyl-CoA 2 | a | 943.2103 (M + NH4)+ | 1.77 (1.66–2.02) | 1.79 (1.61–2.04) | 0.98 | 0.91 |
| Hexanoylglycine 2 | a, b | 174.1123 (M + H)+ | 0.20 (0.12–0.26) | 0.13 (0.08–0.19) | 0.02 * | 0.15 |
| Heptanoylglycine 2 | a | 229.1544 (M + H)+ | 0.64 (0.50–0.97) | 0.65 (0.49–0.81) | 0.58 | 0.69 |
| Gamma-Butyrolactone/ | a | 85.0293 (M – H)− | 42.9 (25.08–58.13) | 48.37 (34.67–65.61) | 0.32 | 0.68 |
| But-2-enoic/Isocrotonic acid 2 | a, b | 631.3089 (M – H)− | 0.01 (0.00–0.03) | 0.02 (0.01–0.06) | 0.01 * | 0.63 |
| butyl 2-dodecanoic acid/ 5-Tetra dodecanoic acid 2 | a | 225.1859 (M – H)− | 0.09 (0.04–0.19) | 0.06 (0.01–0.10) | 0.05 t | 0.81 |
| caproic acid 1 | a | 115.0763 (M – H)− | 0.13 (0.11–0.15) | 0.14 (0.11–0.18) | 0.46 | 0.26 |
| 3-hydroxycapric acid 2 | a, b, c | 187.1339 (M – H)− | 0.43 (0.26–0.81) | 0.62 (0.50–1.11) | 0.01 * | 0.97 |
| Geranic acid 2 | 167.1077 (M – H)− | 0.09 (0.07–0.22) | 0.08 (0.06–0.16) | 0.13 | 0.03 | |
| Sebacic acid 1 | a, c | 261.1345 (M-CH3COO)− | 0.10 (0.07–0.18) | 0.13 (0.08–0.19) | 0.18 t | 0.72 |
| 3-Hydroxysebacic acid 2 | a, c | 217.1081 (M – H)− | 0.04 (0.03–0.06) | 0.06 (0.03–0.07) | 0.07 t | 0.68 |
| 3,4-Methylenesebacic acid 2 | a | 225.1132 (M – H)− | 0.04 (0.03–0.06) | 0.03 (0.02–0.04) | 0.12 t | 0.82 |
| 2-Hydroxybutyric acid 1 | a, b, c | 103.0399 (M – H)− | 2.93 (2.35–3.72) | 3.85 (3.05–4.81) | 0.005 * | 0.77 |
| 2-hydroxy-3-methylbutyric acid 1 | a, b, c | 117.0555 (M – H)− | 0.99 (0.81–1.82) | 1.52 (1.07–2.07) | 0.01 * | 0.06 |
| pyridosine 2 | a, c | 253.1195 (M – H)− | 0.20 (0.09–0.28) | 0.11 (0.07–0.22) | 0.06 t | 0.17 |
| Glycerophosphorylcholine 2 | a, c | 292.0724 (M – H)− | 0.68 (0.49–0.96) | 0.58 (0.41–0.71) | 0.07 t | 0.40 |
| N-Heptanoylglycine 2 | a, b | 186.1135 (M – H)− | 0.93 (0.47–1.83) | 0.61 (0.40–1.16) | 0.07 t | 0.14 |
| Butyryl glycine/Saccharopine 2 | a | 335.1455 * (M + Fa − H)− | 0.22 (0.11–0.53) | 0.28 (0.08–0.51) | 0.58 | 0.62 |
| 2-Phenylglycine 2 | a, c | 150.0559 (M – H)− | 0.14 (0.09–0.22) | 0.17 (0.10–0.29) | 0.11 t | 0.08 |
| Cis-aconitic acid 1 | a | 154.9983 (M-H2O – H) − | 1.33 (0.58–2.27) | 1.73 (1.28–2.49) | 0.09 t | 0.85 |
| Pyruvic acid 1 | a, b, c | 147.0297 (M-CH3COO)− | 2.15 (1.27–3.49) | 3.55 (1.94–6.10) | 0.03 * | 0.95 |
| Citraconic 1 | a, b, c | 129.0192 (M – H)− | 13.82 (9.49–26.19) | 21.43 (13.82–29.91) | 0.02 * | 0.95 |
| 2-Keto-glutaramic acid 2 | a, c | 144.0302 (M – H)− | 0.38 (0.30–0.44) | 0.37 (0.31–0.58) | 0.21 | 0.44 |
| Panthothenic acid 1 | a, c | 200.0929 (M-H2O – H)− | 0.09 (0.06–0.11) | 0.10 (0.08–0.11) | 0.51 | 0.007 |
| 4-Heptenal 2 | a, b | 111.0814 (M – H)− | 0.43 (0.33–0.50) | 0.35 (0.26–0.45) | 0.04 * | 0.55 |
| 2-Methylpentanal 2 | a | 99.0814 (M – H)− | 0.12 (0.09–0.13) | 0.10 (0.09–0.12) | 0.06 t | 0.98 |
| Undecenal 2 | a, b, c | 167.1440 (M – H)− | 0.08 (0.06–0.12) | 0.06 (0.04–0.13) | 0.006 * | 0.02 |
| Methyl 2-octynoate 2 | a | 153.0919 (M – H)− | 0.10 (0.07–0.13) | 0.07 (0.06–0.11) | 0.09 t | 0.06 |
| 4-Methylphenyl-acetaldehyde 2 | a | 133.0658 (M – H)− | 0.07 (0.05–0.11) | 0.06 (0.05–0.09) | 0.04 * | 0.14 |
| 4-Hydroxynonenal 2 | a, c | 155.1077 (M – H)− | 0.06 (0.04–0.09) | 0.07 (0.05–0.10) | 0.13 t | 0.79 |
| cis-4-Decenedioic acid 2 | a, b, c | 199.0973 (M – H)− | 0.07 (0.05–0.11) | 0.10 (0.07–0.16) | 0.01 * | 0.94 |
| Tetradecanedioic acid 1 | a, c | 257.1761 (M – H)− | 0.08 (0.05–0.12) | 0.12 (0.08–0.19) | 0.07 t | 0.62 |
| Dodecanedioic acid 2 | a, c | 229.1445 (M – H)− | 0.41 (0.30–0.56) | 0.35 (0.30–0.54) | 0.42 | 0.01 |
| Heptanoic acid 2 | a, c | 129.0920 (M – H)− | 0.17 (0.14–0.21) | 0.14 (0.10–0.19) | 0.06 t | 0.74 |
| 2-benzyloctanoic acid 2 | a, b, c | 233.1544 (M – H)− | 1.45 (0.78–2.31) | 0.87 (0.61–1.45) | 0.007 * | 0.81 |
| N-methylethanolaminium phosphate 2 | a, b, c | 136.0165 (M–H2O – H)− | 0.36 (0.27–0.51) | 0.26 (0.19–0.30) | <0.0001 ** | 0.81 |
| Phosphorylcholine 1 | a, | 206.0551 (M + Na)+ | 5.78 (4.26–6.63) | 4.03 (0.68–5.67) | 0.001 * | 0.21 |
| Glycerophosphocholin 2 | a | 280.0917 (M + Na)+ | 18.88 (9.66–30.18) | 16.98 (3.54–24.57) | 0.12 t | 0.57 |
| Choline 1 | a, | 105.11080 (M + H)+ | 2.67 (2.25–3.66) | 3.30 (2.74–4.65) | 0.008 * | 0.02 |
| Glucuronide/oligosides | ||||||
| Dihydrocaffeic acid 3-O-glucuronide 2 | a, b, c | 383.0763 (M + Na)+ | 1.15 (0.87–1.29) | 1.05 (0.86–1.23) | 0.49 | 0.51 |
| 2-Fucosyllactose 2 | a, c | 511.1629 (M + H)+ | 106.6 (82.1–152.5) | 122.6 (98.5–148.7) | 0.34 | 0.79 |
| N-acetyl-D-glucosamine 2 | a | 244.0788 (M + Na)+ | 2.94 (2.71–3.51) | 3.20 (2.55–3.81) | 0.74 | 0.68 |
| Lacto-N-fucopentaose-2 2 | a, b | 876.2936 (M + Na)+ | 9.29 (7.62–12.68) | 10.56 (8.07–15.04) | 0.15 t | 0.72 |
| Saccharopine 2 | a, c | 335.1455 (M-CH3COO)− | 0.22 (0.11–0.53) | 0.28 (0.08–0.51) | 0.58 | 0.62 |
Values are medians (25% and 75% percentiles) from metabolites abundances from week 2 to week 4 of lactation period. Metabolites’ annotation level in brackets: 1: identification level, definitively annotated with our home data base (i.e., based upon characteristic physicochemical properties of chemical reference standards (m/z, RT) and their MS/MS spectra compared to those of breastmilk QC); 2: putatively annotated compounds (i.e., without chemical reference standards, based upon physicochemical properties and MS/MS spectral similarity with public/commercial spectral libraries). (a) VIP in AoV-PLS/LDA ESI+ or ESI− model, (b) loadings in MB-PLS model, (c) loadings in ACC model; when the letters (a, b or c) are in italic, that means that the significance of metabolites, as VIP or loadings in statistical models, is just a trend. Variables were considered as significantly modified between the two groups of infants’ growth (Mann-Whitney U test) when their multiple comparisons adjusted P-values (i.e., FDR corrected-MW q-value) was < 0.05. FDR-corrected MW q-value was labelled in exposant: *: FDR-corrected q-value < 0.05; **: FDR-corrected MW q-value < 0.01; t: FDR-corrected MW q-value < 0.1. Predictive ability of metabolites for infant weight growth was considered reliable when FDR-corrected MLR q-value was < 0.1 (and labelled in exposant as #).