#METABOLOMICS WORKBENCH KDSpencer77_20230821_115049 DATATRACK_ID:4237 STUDY_ID:ST002837 ANALYSIS_ID:AN004640 PROJECT_ID:PR001776 VERSION 1 CREATED_ON August 22, 2023, 12:07 pm #PROJECT PR:PROJECT_TITLE Bacterial tryptophan metabolites increased by prebiotic galactooligosaccharide PR:PROJECT_TITLE reduce microglial reactivity and are associated with lower anxiety-like behavior PR:PROJECT_SUMMARY Prebiotic galactooligosaccharides (GOS) reduce anxiety-like behaviors in mice PR:PROJECT_SUMMARY and humans. However, the biological pathways behind these behavioral changes are PR:PROJECT_SUMMARY not well understood. To begin to study these pathways, C57BL/6 mice were fed a PR:PROJECT_SUMMARY standard diet with or without GOS supplementation for 3 weeks prior to testing PR:PROJECT_SUMMARY on the open field. After behavioral testing, colonic contents and serum were PR:PROJECT_SUMMARY collected for bacteriome (16S rRNA gene sequencing, colonic contents only) and PR:PROJECT_SUMMARY metabolome (UPLC-MS, colonic contents and serum data) analyses. As expected, GOS PR:PROJECT_SUMMARY significantly reduced anxiety-like behavior (i.e., increased time in the center PR:PROJECT_SUMMARY (p < 0.05)). Time in the center was significantly correlated with serum PR:PROJECT_SUMMARY methyl-indole-3-acetate (mI3A). This metabolite, which is a methylated form of PR:PROJECT_SUMMARY indole-3-acetate, is derived from bacterial metabolism of tryptophan. Sequencing PR:PROJECT_SUMMARY analyses showed that GOS significantly increased Akkermansia, which is known to PR:PROJECT_SUMMARY metabolize both GOS and tryptophan. To test the hypothesis that mI3A can reduce PR:PROJECT_SUMMARY anxiety-like behavior and affect microglial activity, we first tested mI3A PR:PROJECT_SUMMARY effects on LPS-stimulated BV2 microglia. Cells treated with mI3A produced PR:PROJECT_SUMMARY significantly less CCL2 and TNF-α than vehicle-treated cells (p<.05). We then PR:PROJECT_SUMMARY treated mice with an intraperitoneal injection of mI3A or vehicle control, and PR:PROJECT_SUMMARY found that mice given mI3A had lower CCL2 in the prefrontal cortex and PR:PROJECT_SUMMARY hippocampus, as well as a reduction in a composite behavioral score in the open PR:PROJECT_SUMMARY field. Together, these data support a novel pathway through which GOS reduces PR:PROJECT_SUMMARY anxiety-like behaviors in mice, and suggests that the bacterial metabolite mI3A, PR:PROJECT_SUMMARY which is elevated by GOS, reduces microglial CCL2, which in turn reduces PR:PROJECT_SUMMARY anxiety-like behavior. PR:INSTITUTE National Center for Advancing Translational Sciences PR:LAST_NAME Spencer PR:FIRST_NAME Kyle PR:ADDRESS 9800 Medical Center Dr, Rockville, MD 20850 PR:EMAIL kyle.spencer@nih.gov PR:PHONE 9897084858 #STUDY ST:STUDY_TITLE Bacterial tryptophan metabolites increased by prebiotic galactooligosaccharide ST:STUDY_TITLE reduce microglial reactivity and are associated with lower anxiety-like behavior ST:STUDY_TITLE (Blood) ST:STUDY_SUMMARY Prebiotic galactooligosaccharides (GOS) reduce anxiety-like behaviors in mice ST:STUDY_SUMMARY and humans. However, the biological pathways behind these behavioral changes are ST:STUDY_SUMMARY not well understood. To begin to study these pathways, C57BL/6 mice were fed a ST:STUDY_SUMMARY standard diet with or without GOS supplementation for 3 weeks prior to testing ST:STUDY_SUMMARY on the open field. After behavioral testing, colonic contents and serum were ST:STUDY_SUMMARY collected for bacteriome (16S rRNA gene sequencing, colonic contents only) and ST:STUDY_SUMMARY metabolome (UPLC-MS, colonic contents and serum data) analyses. As expected, GOS ST:STUDY_SUMMARY significantly reduced anxiety-like behavior (i.e., increased time in the center ST:STUDY_SUMMARY (p < 0.05)). Time in the center was significantly correlated with serum ST:STUDY_SUMMARY methyl-indole-3-acetate (mI3A). This metabolite, which is a methylated form of ST:STUDY_SUMMARY indole-3-acetate, is derived from bacterial metabolism of tryptophan. Sequencing ST:STUDY_SUMMARY analyses showed that GOS significantly increased Akkermansia, which is known to ST:STUDY_SUMMARY metabolize both GOS and tryptophan. To test the hypothesis that mI3A can reduce ST:STUDY_SUMMARY anxiety-like behavior and affect microglial activity, we first tested mI3A ST:STUDY_SUMMARY effects on LPS-stimulated BV2 microglia. Cells treated with mI3A produced ST:STUDY_SUMMARY significantly less CCL2 and TNF-α than vehicle-treated cells (p<.05). We then ST:STUDY_SUMMARY treated mice with an intraperitoneal injection of mI3A or vehicle control, and ST:STUDY_SUMMARY found that mice given mI3A had lower CCL2 in the prefrontal cortex and ST:STUDY_SUMMARY hippocampus, as well as a reduction in a composite behavioral score in the open ST:STUDY_SUMMARY field. Together, these data support a novel pathway through which GOS reduces ST:STUDY_SUMMARY anxiety-like behaviors in mice, and suggests that the bacterial metabolite mI3A, ST:STUDY_SUMMARY which is elevated by GOS, reduces microglial CCL2, which in turn reduces ST:STUDY_SUMMARY anxiety-like behavior. ST:INSTITUTE National Center for Advancing Translational Sciences ST:LAST_NAME Spencer ST:FIRST_NAME Kyle ST:ADDRESS 9800 Medical Center Dr, Rockville, MD 20850 ST:EMAIL kyle.spencer@nih.gov ST:PHONE 9897084858 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS - NACH-00271 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00272 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00273 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00274 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00275 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00276 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00277 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00278 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00279 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00280 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00281 GROUP_ID:CON #COLLECTION CO:COLLECTION_SUMMARY After euthanasia the serum of the mice were collected and sent to Metabolon Inc CO:COLLECTION_SUMMARY for UPLC-MS Analysis. CO:SAMPLE_TYPE Blood (serum) #TREATMENT TR:TREATMENT_SUMMARY The mice were fed either a control diet or a diet supplemented with 10% TR:TREATMENT_SUMMARY galactooligosaccharide for 3 weeks. After the 3 weeks had elapsed the mice were TR:TREATMENT_SUMMARY euthanized and the colonic contents were collected. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY The colonic contents were sent to Metabolon who then performed the sample SP:SAMPLEPREP_SUMMARY preparation prior to UPLC-MS analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY HILIC (LC/MS Polar Neg) CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Waters Acquity CH:COLUMN_NAME Waters Acquity BEH Amide (150 x 2.1mm, 1.7um) CH:SOLVENT_A - CH:SOLVENT_B - CH:FLOW_GRADIENT - CH:FLOW_RATE - CH:COLUMN_TEMPERATURE - #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE Other MS:ION_MODE NEGATIVE MS:MS_COMMENTS Metabolon (LC/MS Polar) #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Relative Abundance MS_METABOLITE_DATA_START Samples NACH-00271 NACH-00272 NACH-00273 NACH-00274 NACH-00275 NACH-00276 NACH-00277 NACH-00278 NACH-00279 NACH-00280 NACH-00281 Factors GROUP_ID:GOS GROUP_ID:GOS GROUP_ID:GOS GROUP_ID:GOS GROUP_ID:GOS GROUP_ID:CON GROUP_ID:CON GROUP_ID:CON GROUP_ID:CON GROUP_ID:CON GROUP_ID:CON 2,3-dihydroxyisovalerate 0.3524 1 0.8854 0.9658 1.2558 0.9297 1.064 0.9403 1.0347 1.1605 1.3819 2,6-dihydroxybenzoic acid 0.578 0.8196 0.8195 0.8451 1.009 1.137 0.9763 1 1.0077 1.2007 1.0398 2-aminoadipate 1 1.1816 1.3073 0.9325 0.6694 1.2555 0.9889 0.7893 1.0177 0.9755 1.0258 2-hydroxy-4-(methylthio)butanoic acid 1.2152 0.959 0.7173 0.8123 1.8163 1.189 1.1444 1.5166 0.9706 1 0.9619 2-hydroxyadipate 1.9462 1.2701 0.8417 0.7715 1.1181 1 1.0602 1.0157 0.6656 0.8495 0.9195 2-hydroxybutyrate/2-hydroxyisobutyrate 0.8221 1.1547 1 0.9365 1.0983 1.3549 1.1869 0.8181 1.0022 0.8744 0.8004 2-hydroxyphenylacetate 0.7211 0.7922 1.4082 1.1942 1.0168 1.0804 0.953 0.8084 0.9035 1 1.5297 2-isopropylmalate 0.6264 1.4726 1.3279 0.4417 1 1.1752 2.1994 0.9138 0.9041 1.1716 0.654 2-keto-3-deoxy-gluconate 0.9997 1.5409 1.444 1.1354 0.8705 0.9661 1.0003 0.7888 0.7888 0.9441 1.0146 2-oxoadipate 1.511 1.4418 1.3026 0.8688 1.4581 1.2763 0.882 1 0.9351 0.8547 0.9951 2R,3R-dihydroxybutyrate 0.7218 0.876 0.9595 0.9765 1.021 1.1437 1.0758 1 0.9699 1.0303 1.0156 2S,3R-dihydroxybutyrate 0.7503 0.9594 0.9136 1.094 1.528 1.1513 1.2804 0.9089 0.9714 1 1.0564 3,4-dihydroxybutyrate 0.7414 1.1689 0.914 1.0039 0.8666 1.0916 1.2266 1.3706 0.9035 1 0.9654 3-hydroxy-3-methylglutarate 1 1.5294 0.9526 0.9812 1.4517 1.3329 1.2964 0.8076 1.0233 0.9682 0.8504 3-hydroxyadipate* 0.1945 1.0034 0.4601 0.7576 1.0809 1.0293 1.8278 1 0.8611 1.0974 0.4374 3-hydroxybutyrate (BHBA) 1.4852 0.9433 1.1661 0.8514 1.06 1.3643 1.0195 0.9406 1 0.9648 0.6396 3-hydroxyisobutyrate 1.3798 1.4095 1.0314 0.6037 1.6522 1.3826 0.644 1 0.6125 0.7041 0.9607 3-methylglutaconate 0.9168 1.2282 1.0261 1 1.2116 1.0201 0.8732 0.8322 0.7646 0.7302 1.2419 acetylphosphate 0.5711 0.7521 1.5194 1.4486 0.6085 0.8669 0.5634 1 1.8588 1.3075 4.7926 adipate (C6-DC) 1.01 1.1546 0.5231 0.9643 1.6038 1.2206 1.4937 1 0.8818 0.9224 0.8119 allantoin 0.8788 0.9335 0.9544 1 0.9806 1.1241 1.2443 1.0161 0.9462 1.0451 1.3187 alpha-ketoglutaramate* 1.4855 1.0383 0.9929 0.9549 1.2106 0.989 1.0429 0.9135 0.974 1 1.4097 alpha-ketoglutarate 1.4652 1.4573 0.8308 1.2387 1.6083 1.3517 0.9934 0.6618 1 0.9455 0.2252 arabinose 0.1317 1.1231 1.084 0.1317 0.916 0.8981 1.2577 1.1292 0.1317 0.1317 0.883 arabitol/xylitol 0.9455 1.2658 0.9015 0.8179 1.174 1 1.5304 0.9519 0.8621 1.0593 1.0744 arabonate/xylonate 0.6573 1.4379 1 0.9666 0.9755 1.1719 1.4114 0.7319 0.9779 1.1156 1.0374 ascorbic acid 2-sulfate 0.4635 1.0625 1 0.9239 0.8721 1.1532 1.4478 0.9998 0.9497 1.0733 1.1711 ascorbic acid 3-sulfate* 0.5139 1.4068 1 0.9483 0.8932 1.5549 1.8823 0.9861 1.2124 1.3315 0.9005 caffeic acid sulfate 1.0729 3.0253 14.3167 1 1.915 0.6861 1.1429 0.8618 0.3703 0.9716 0.2321 creatine phosphate 1.0359 0.803 0.4444 1.0799 0.625 1.0773 1.0165 0.5137 1.071 0.9835 0.4444 cysteine s-sulfate 7.1239 1.0583 0.7807 1.2348 1.1608 1.0101 0.9568 0.9884 0.8713 0.8589 1 dihydrocaffeate sulfate (2) 1.2811 1.2306 0.3148 1.179 1.7307 0.3799 0.6574 0.4463 1 1.7406 0.612 dihydroorotate 2.3704 1.5889 0.4288 1.0894 1.6666 1.1384 0.9698 0.5168 1 0.9629 0.1965 erythritol 0.7142 0.726 1 0.7942 0.5654 1.0271 1.0065 1.0939 0.935 1.2148 1.6459 erythronate* 0.6131 1.0239 0.9441 0.9449 1.022 1.0201 1.0749 0.7984 0.8188 1.0188 1 ethylmalonate 0.5148 1.7837 1.0118 1.0239 1 1.202 1.0229 0.6231 0.8852 0.8858 0.7912 fructose 1.6023 1.4383 1 0.7541 1.9562 1.0551 1.0071 0.6765 0.7602 0.7578 0.972 fumarate 1.556 1.716 1.3837 0.7134 1.26 0.9987 1 0.8568 0.8877 0.893 1.237 galactitol (dulcitol) 3.1912 1 1.6817 1.277 0.7923 0.6822 0.9734 1.0772 0.3004 0.5433 2.2888 galactonate 1.2313 1.1532 1.4405 0.8308 0.9484 0.8879 1.2636 1 0.572 0.8884 1.3118 gluconate 2.1287 1.2965 1.0613 0.7339 0.9863 0.9228 1 0.8797 0.7562 1.0032 1.2403 glucose 0.4963 1.2129 0.7931 1.0547 0.9231 1.2181 1.4113 0.8903 1 1.0955 0.6246 glucuronate 2.0401 0.8493 0.9162 1 1.0118 0.8725 1.0325 1.0272 0.9324 0.9633 1.2201 glutarate (C5-DC) 1.2597 1.6802 0.8452 0.7746 1.4234 1.7839 1 0.595 1.5097 0.8744 0.6256 glycerate 0.7954 0.9515 0.9474 1 1.0626 1.0847 1.0721 0.9276 1.0271 0.7942 1.2286 glycerophosphoethanolamine 0.7401 1.0065 1.105 0.8857 0.9755 1 1.0186 0.8088 1.0984 0.9925 2.025 glycerophosphoglycerol 1.2305 1.0395 1.8444 0.5754 0.9465 0.9296 1 0.7973 1.0239 0.8412 1.3181 glycerophosphoinositol* 0.9144 1.0873 0.8366 1.3638 0.9824 0.8417 1.1137 0.8293 1.1876 1 1.7667 glycolate (hydroxyacetate) 2.0611 1.2041 1.5324 0.3771 1.0617 1.0376 0.9103 0.8276 0.3959 0.9624 0.3771 gulonate* 0.6986 1.4936 1.0727 0.8043 1.8243 1 1.378 0.9043 0.8429 1.2411 0.5976 hydantoin-5-propionate 0.4859 1.9597 0.5834 0.9072 2.4082 1 0.8166 1.001 1.2335 0.8306 2.1538 hypotaurine 2.5542 1.0168 1.0181 0.9199 0.8052 0.6914 1.0845 0.9721 0.7309 1 1.3283 isocitric lactone 1.0205 1.5672 1.1328 0.9535 1 1.0623 0.9946 0.8376 0.7459 0.8527 1.5146 lactate 0.8514 1.2576 1 1.0441 1.0328 0.9789 1.0069 0.7955 1.0261 0.9823 0.8984 malate 1.3517 1.5953 1.4631 0.7944 0.9463 1.1005 0.8914 0.7502 1 0.9058 1.4472 maleate 1.4897 1.9382 1.0045 0.9689 1.225 1.1788 0.8546 0.6459 0.8497 1 0.9567 malonate 1 1.0658 0.8955 1.2293 1.018 0.9477 0.8821 0.8306 1.0681 0.7839 1.0449 mannitol/sorbitol 0.8706 1.2859 0.9852 1.1348 1 1.0642 1.3409 0.8731 0.921 1.2153 0.8422 mannonate* 0.7852 1.1244 1.0457 0.8941 0.9367 0.9318 1.4023 1 0.8458 1.2075 1.1434 mannose 0.6586 1 0.6402 1.1919 0.7917 1.323 1.7268 1.348 0.9617 1.1871 0.5685 methylmalonate (MMA) 0.8892 1.4549 0.9913 0.9173 1.139 1.0357 1.2646 0.8347 1 0.9786 1.0069 methylsuccinate 0.94 1.2648 0.9259 0.7999 1 1.1399 1.4543 0.8386 1.0652 1.1174 0.6948 mevalonate 0.9253 0.827 0.8573 0.8813 1.2093 1.1698 1.0163 1.0668 1 0.849 1.2481 myo-inositol 0.7705 1.0278 1.0064 1.2287 0.9791 0.8931 0.9822 0.8099 1.0659 1 1.8224 N-acetylalanine 1.0372 0.9326 0.9614 1 0.9518 1.1374 1.1654 1.0551 0.9265 0.9257 1.0676 N-acetylaspartate (NAA) 0.8453 0.9977 1.5422 1.227 0.7333 1.1977 0.9601 1 1.3008 0.9548 2.5979 N-acetylglucosamine 6-phosphate 2.1018 1 2.3027 0.8573 0.8537 0.7222 0.8978 1.0137 1.2786 0.973 2.6943 N-acetylglycine 0.5333 1.0818 0.9441 0.9927 1.1042 1.0202 1.045 0.9381 0.8473 1 1.1794 N-acetylneuraminate 0.8721 0.9522 1.133 0.9642 0.9016 1.1102 1 0.9864 1.1206 1.1869 1.8118 N-acetylserine 0.8514 1 0.8966 1.0099 1.1184 0.9517 1.099 1.0251 0.982 0.975 1.2404 N-formylanthranilic acid 2.0542 0.8359 1.5464 1.1509 1.1864 0.8896 0.5404 0.8028 0.7974 1 2.7305 N2,N5-diacetylornithine 1.0136 1.0247 0.8684 1.1829 1.1445 0.9006 0.9864 0.7902 0.5466 0.5466 1.1168 N2-acetyllysine 0.499 1.4246 1.2056 0.875 0.9435 1.5033 1.3141 0.9271 1 1.392 0.839 N6-acetyllysine 0.7603 0.9763 1.0394 0.7839 1.0113 1.2079 0.9974 1.0794 0.9141 1.0352 1 orotate 1.6725 0.9977 1.3682 1.0994 0.7404 1.1103 0.7895 0.8122 1 0.85 1.5385 orotidine 0.9007 1.0826 1 1.0654 0.726 1.057 0.9877 0.7126 1.0111 0.9855 1.4486 pentose acid* 0.6848 1.2211 1.0086 0.6848 0.9914 0.6848 1.13 0.6848 0.6848 0.6848 0.7009 perfluorooctanesulfonate (PFOS) 1.4219 1.1989 1.0154 0.834 0.8664 1.1853 1 0.7663 1.0352 0.9649 0.774 pimelate (C7-DC) 0.3783 0.3761 0.5395 0.3761 1.2026 1.1445 1.5082 0.912 1.088 1.1266 0.4106 pyruvate 1.3509 1.306 0.7708 1 0.9822 1.072 1.0538 0.7881 0.9734 1.0117 0.595 ribitol 1.0257 1.4196 0.917 1 1.1079 0.974 1.2754 0.8954 0.895 0.9592 1.093 ribonate 0.6724 1.279 0.9821 0.7795 1 1.5607 1.684 1.0459 0.9937 1.1375 0.8842 ribose 2.8238 0.2468 0.4636 2.5476 0.6316 0.3368 0.2468 1.4899 1 1.1057 0.2468 ribulonate/xylulonate/lyxonate* 0.565 1.1807 0.8087 1 0.8978 1.1581 1.294 0.8673 1.0353 1.0847 0.7148 ribulose/xylulose 0.708 0.7998 1 1.1558 0.708 0.708 0.708 1.1127 0.991 1.1492 0.708 S-methylcysteine 1.1221 0.6976 0.686 0.7748 1.1553 1.1669 0.836 1.2822 0.686 1.1153 0.8847 salicylate 1.5522 0.934 1.1883 1.1174 1.0643 0.9357 0.7439 0.6683 0.411 0.411 1.7571 sedoheptulose 0.9952 1.0773 0.8526 0.5925 1.8136 0.6096 1.0048 0.735 0.5925 1.0167 1.1822 sphingosine 1-phosphate 1.4439 0.8902 0.8282 1.0862 1 0.9438 1.0512 0.9337 1.118 1.0868 0.7913 succinate 0.8431 1.1858 0.8619 0.8425 1.0161 1.1377 1.1361 0.7878 1.077 1 0.8001 sucrose 0.8221 2.4538 1.62 0.9201 3.7637 0.9832 1.5164 0.9398 0.8933 1 2.5381 taurine 0.9042 1 1.0503 1.0044 0.8177 0.9444 1.0232 0.8529 1.0007 0.9068 1.4653 threonate 0.5704 1.1033 1.0811 0.7084 1 1.114 1.1924 0.769 0.8307 1.0143 0.7907 tricarballylate 0.0733 3.0085 2.6125 1.1375 3.5927 0.6248 1 0.4856 0.733 1.0063 0.5161 xylose 0.6976 0.9141 0.9142 0.6976 1.0113 1.2889 0.9887 1.064 0.6976 0.6976 1.1408 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name SUPER_PATHWAY SUB_PATHWAY COMP_ID PLATFORM CHEMICAL_ID RI MASS CAS PUBCHEM CHEMSPIDER KEGG HMDB_ID 2,3-dihydroxyisovalerate Xenobiotics Food Component/Plant 38276 LC/MS Polar 100002417 1050 133.05063 1756-18-9 677 657 C04039 HMDB12141 2,6-dihydroxybenzoic acid Xenobiotics Drug - Topical Agents 63042 LC/MS Polar 100020837 729 153.01933 303-07-1 9338 8974 HMDB13676 2-aminoadipate Amino Acid Lysine Metabolism 6146 LC/MS Polar 381 3500 160.06153 542-32-5;1118-90-7 469 456 C00956 HMDB00510 2-hydroxy-4-(methylthio)butanoic acid Amino Acid Methionine, Cysteine, SAM and Taurine Metabolism 63739 LC/MS Polar 100021372 1065 149.02778 583-91-5 2-hydroxyadipate Lipid Fatty Acid, Dicarboxylate 31934 LC/MS Polar 100001153 3000 161.04554 18294-85-4 193530 167943 C02360 HMDB00321 2-hydroxybutyrate/2-hydroxyisobutyrate Amino Acid Glutathione Metabolism 52281 LC/MS Polar 100008928 1258 103.04006 2-hydroxyphenylacetate Amino Acid Phenylalanine Metabolism 1432 LC/MS Polar 235 858.6 151.04006 614-75-5 11970 11476 C05852 HMDB00669 2-isopropylmalate Xenobiotics Food Component/Plant 15667 LC/MS Polar 100000409 2605 175.06119 3237-44-3 77 76 C02504 HMDB00402 2-keto-3-deoxy-gluconate Xenobiotics Food Component/Plant 48141 LC/MS Polar 100005946 1900 177.04046 17510-99-5 161227 141630 C00204 HMDB01353 2-oxoadipate Amino Acid Lysine Metabolism 38347 LC/MS Polar 92 2635 159.0299 3184-35-8 71 70 C00322 HMDB00225 2R,3R-dihydroxybutyrate Lipid Fatty Acid, Dihydroxy 63109 LC/MS Polar 100002367 1543 119.03498 759-06-8 13120901 17215960 HMDB00498 2S,3R-dihydroxybutyrate Lipid Fatty Acid, Dihydroxy 62950 LC/MS Polar 100002284 1660 119.03498 5057-93-2 10964471 9139682 HMDB02453 3,4-dihydroxybutyrate Lipid Fatty Acid, Dihydroxy 62952 LC/MS Polar 100001730 2204 119.03498 51267-44-8 3-hydroxy-3-methylglutarate Lipid Mevalonate Metabolism 531 LC/MS Polar 112 2850 161.04555 503-49-1 1662 4573695 C03761 HMDB00355 3-hydroxyadipate* Lipid Fatty Acid, Dicarboxylate 62069 LC/MS Polar 100004396 3131 161.04554 151913 133894 HMDB00345 3-hydroxybutyrate (BHBA) Lipid Ketone Bodies 542 LC/MS Polar 254 1480 103.04007 625-72-9 441 428 C01089 HMDB00357 3-hydroxyisobutyrate Amino Acid Leucine, Isoleucine and Valine Metabolism 1549 LC/MS Polar 111 1619 103.04007 2068-83-9 87 10140307 C06001 HMDB00336 3-methylglutaconate Amino Acid Leucine, Isoleucine and Valine Metabolism 57747 LC/MS Polar 100002458 2700 99.04518 5746-90-7 1551553 1267861 HMDB00522 acetylphosphate Energy Oxidative Phosphorylation 15488 LC/MS Polar 1211 4013.9 138.98018 94249-01-1 186 181 C00227 HMDB01494 adipate (C6-DC) Lipid Fatty Acid, Dicarboxylate 21134 LC/MS Polar 100000863 3000 145.05063 124-04-9 196 191 C06104 HMDB00448 allantoin Nucleotide Purine Metabolism, (Hypo)Xanthine/Inosine containing 1107 LC/MS Polar 1002 1672 157.03671 97-59-6 204 199 C02350 HMDB00462 alpha-ketoglutaramate* Amino Acid Glutamate Metabolism 62101 LC/MS Polar 100002397 1916 144.03023 18465-19-5 48 alpha-ketoglutarate Energy TCA Cycle 528 LC/MS Polar 93 2700 145.01425 305-72-6;328-50-7;22202-68-2 51 50 C00026 HMDB00208 arabinose Carbohydrate Pentose Metabolism 575 LC/MS Polar 828 1804.5 195.05103 28697-53-2 66308 59687 C00216 HMDB00646 arabitol/xylitol Carbohydrate Pentose Metabolism 48885 LC/MS Polar 100006430 1932.4 151.0612 6912 C01904 arabonate/xylonate Carbohydrate Pentose Metabolism 48255 LC/MS Polar 100006115 2700 165.04046 ascorbic acid 2-sulfate Cofactors and Vitamins Ascorbate and Aldarate Metabolism 63590 LC/MS Polar 100009329 3042 254.98162 86484 77998 ascorbic acid 3-sulfate* Cofactors and Vitamins Ascorbate and Aldarate Metabolism 63687 LC/MS Polar 100020409 2025 254.98146 11425365 9600241 caffeic acid sulfate Xenobiotics Food Component/Plant 53254 LC/MS Polar 100009337 1307 258.99179 30777608 HMDB41708 creatine phosphate Amino Acid Creatine Metabolism 33951 LC/MS Polar 100000112 3831 210.02853 922-32-7 9548602 567 C02305 HMDB01511 cysteine s-sulfate Amino Acid Methionine, Cysteine, SAM and Taurine Metabolism 22176 LC/MS Polar 100000808 2273 199.96928 1637-71-4 115015 102939 C05824 HMDB00731 dihydrocaffeate sulfate (2) Xenobiotics Food Component/Plant 62524 LC/MS Polar 100020822 1328 261.00744 49844181 dihydroorotate Nucleotide Pyrimidine Metabolism, Orotate containing 601 LC/MS Polar 923 1910 157.02548 155-54-4 648 628 C00337 HMDB03349 erythritol Xenobiotics Food Component/Plant 20699 LC/MS Polar 100000846 1491 167.05611 149-32-6 222285 13835932 C00503 HMDB02994 erythronate* Carbohydrate Aminosugar Metabolism 42420 LC/MS Polar 100001320 2186 135.02989 88759-55-1 2781043 2061231 HMDB00613 ethylmalonate Amino Acid Leucine, Isoleucine and Valine Metabolism 15765 LC/MS Polar 2054 2785 131.03498 601-75-2 11756 11263 HMDB00622 fructose Carbohydrate Fructose, Mannose and Galactose Metabolism 577 LC/MS Polar 878 2065 179.05611 57-48-7 5984 5764 C00095 HMDB00660 fumarate Energy TCA Cycle 1643 LC/MS Polar 330 3084 115.00368 100-17-8 444972 10197150 C00122 HMDB00134 galactitol (dulcitol) Carbohydrate Fructose, Mannose and Galactose Metabolism 1117 LC/MS Polar 1003 2360 181.07176 608-66-2 11850 11357 C01697 HMDB00107 galactonate Carbohydrate Fructose, Mannose and Galactose Metabolism 27719 LC/MS Polar 100001026 3085 195.05102 299-28-5 128869 114198 C00880 HMDB00565 gluconate Xenobiotics Food Component/Plant 587 LC/MS Polar 338 2922 195.05102 527-07-1 10690 10240 C00257 HMDB00625 glucose Carbohydrate Glycolysis, Gluconeogenesis, and Pyruvate Metabolism 20488 LC/MS Polar 572 2342 179.05611 50-99-7 5793 71358 C00031 HMDB00122 glucuronate Carbohydrate Aminosugar Metabolism 15443 LC/MS Polar 100000257 3233.3 193.03537 207300-70-7 444791 58552 C00191 HMDB00127 glutarate (C5-DC) Lipid Fatty Acid, Dicarboxylate 396 LC/MS Polar 339 2900 131.03498 110-94-1 743 3618533 C00489 HMDB00661 glycerate Carbohydrate Glycolysis, Gluconeogenesis, and Pyruvate Metabolism 1572 LC/MS Polar 1052 2070.4 105.01933 600-19-1 752 732 C00258 HMDB00139 glycerophosphoethanolamine Lipid Phospholipid Metabolism 37455 LC/MS Polar 100001620 3075 214.04859 33049-08-0 123874 110410 C01233 HMDB00114 glycerophosphoglycerol Lipid Glycerolipid Metabolism 48857 LC/MS Polar 100001619 2430 245.04317 439964 388990 C03274 glycerophosphoinositol* Lipid Phospholipid Metabolism 47155 LC/MS Polar 100001621 3850 333.05922 16824-65-0 167572 glycolate (hydroxyacetate) Xenobiotics Chemical 15737 LC/MS Polar 203 1790.4 159.01073 79-14-1 757 737 C00160 HMDB00115 gulonate* Cofactors and Vitamins Ascorbate and Aldarate Metabolism 46957 LC/MS Polar 100001586 2750 195.05102 20246-53-1 152304 7969943 C00257 HMDB03290 hydantoin-5-propionate Amino Acid Histidine Metabolism 40473 LC/MS Polar 100002514 2080 171.04113 5624-26-0 782 761 C05565 HMDB01212 hypotaurine Amino Acid Methionine, Cysteine, SAM and Taurine Metabolism 590 LC/MS Polar 358 2763.4 108.01247 300-84-5 107812 96959 C00519 HMDB00965 isocitric lactone Energy TCA Cycle 54724 LC/MS Polar 100009239 2970 173.00916 4702-32-3 98259 88729 lactate Carbohydrate Glycolysis, Gluconeogenesis, and Pyruvate Metabolism 527 LC/MS Polar 482 1468.8 89.02442 79-33-4 612 592 C00186 HMDB00190 malate Energy TCA Cycle 1303 LC/MS Polar 409 3343.1 133.01425 6915-15-7 525 510 C00149 HMDB00156 maleate Lipid Fatty Acid, Dicarboxylate 20676 LC/MS Polar 100000707 2640 115.00368 110-16-7 444266 392248 C01384 HMDB00176 malonate Lipid Fatty Acid Synthesis 15872 LC/MS Polar 818 3447 103.00368 141-82-2;26522-22-85-0 867 844 C00383 HMDB00691 mannitol/sorbitol Carbohydrate Fructose, Mannose and Galactose Metabolism 46142 LC/MS Polar 100001740 2320 181.07176 5780 440 C00794 HMDB00247 mannonate* Xenobiotics Food Component/Plant 62864 LC/MS Polar 100003695 2736 195.05102 642-99-9 3246006 2496757 mannose Carbohydrate Fructose, Mannose and Galactose Metabolism 584 LC/MS Polar 803 2200 179.05611 3458-28-4 18950 141983 C00159 HMDB00169 methylmalonate (MMA) Lipid Fatty Acid Metabolism (also BCAA Metabolism) 1496 LC/MS Polar 418 3078.4 117.01933 516-05-2 487 473 C02170 HMDB00202 methylsuccinate Amino Acid Leucine, Isoleucine and Valine Metabolism 15745 LC/MS Polar 2051 2800 131.03498 498-21-5 10349 9922 HMDB01844 mevalonate Lipid Mevalonate Metabolism 39583 LC/MS Polar 30 1462 147.06628 96949-03-0 439230 388367 C02104 HMDB00227 myo-inositol Lipid Inositol Metabolism 1124 LC/MS Polar 363 3506.3 225.06159 87-89-8 892 10239179 C00137 HMDB00211 N-acetylalanine Amino Acid Alanine and Aspartate Metabolism 1585 LC/MS Polar 1110 1564.8 130.05096 97-69-8 88064 79449 C02847 HMDB00766 N-acetylaspartate (NAA) Amino Acid Alanine and Aspartate Metabolism 22185 LC/MS Polar 100000787 3143 174.04079 997-55-7;997-55-7 65065 58576 C01042 HMDB00812 N-acetylglucosamine 6-phosphate Carbohydrate Aminosugar Metabolism 15107 LC/MS Polar 1213 4114 300.04899 102029-88-9 439219 8216065 C00357 HMDB02817 N-acetylglycine Amino Acid Glycine, Serine and Threonine Metabolism 27710 LC/MS Polar 100001006 1780 116.03531 543-24-8 10972 10507 HMDB00532 N-acetylneuraminate Carbohydrate Aminosugar Metabolism 32377 LC/MS Polar 1162 3072.6 308.0987 131-48-6 439197 10292217 C00270 HMDB00230 N-acetylserine Amino Acid Glycine, Serine and Threonine Metabolism 37076 LC/MS Polar 100001851 2000 146.04588 97-14-3 65249 58744 HMDB02931 N-formylanthranilic acid Amino Acid Tryptophan Metabolism 43549 LC/MS Polar 100004561 900 164.03531 3342-77-6 101399 91624 C05653 HMDB04089 N2,N5-diacetylornithine Amino Acid Urea cycle; Arginine and Proline Metabolism 43591 LC/MS Polar 100004575 1650 215.10373 39825-23-5 65977 8573834 N2-acetyllysine Amino Acid Lysine Metabolism 36751 LC/MS Polar 100001721 3372.6 187.10881 1946-82-3 92907 83869 C12989 HMDB00446 N6-acetyllysine Amino Acid Lysine Metabolism 36752 LC/MS Polar 100001734 2612.6 187.10881 692-04-6 92832 83801 C02727 HMDB00206 orotate Nucleotide Pyrimidine Metabolism, Orotate containing 1505 LC/MS Polar 445 1638.1 155.00983 50887-69-9 967 942 C00295 HMDB00226 orotidine Nucleotide Pyrimidine Metabolism, Orotate containing 35172 LC/MS Polar 100001416 2250 287.05209 314-50-1 92751 83729 HMDB00788 pentose acid* Partially Characterized Molecules Partially Characterized Molecules 63264 LC/MS Polar 100021467 2180 165.04046 perfluorooctanesulfonate (PFOS) Xenobiotics Chemical 57564 LC/MS Polar 100010955 662 498.93021 1763-23-1 74483 67068 C18142 HMDB59586 pimelate (C7-DC) Lipid Fatty Acid, Dicarboxylate 15704 LC/MS Polar 100000101 2745 159.06628 111-16-0 385 376 C02656 HMDB00857 pyruvate Carbohydrate Glycolysis, Gluconeogenesis, and Pyruvate Metabolism 48990 LC/MS Polar 823 1083 87.00877 127-17-3 1060 96901 C00022 HMDB00243 ribitol Carbohydrate Pentose Metabolism 15772 LC/MS Polar 100000406 1789.6 151.06119 488-81-3 6912 10254628 C00474 HMDB00508 ribonate Carbohydrate Pentose Metabolism 27731 LC/MS Polar 100001007 2425 165.04046 8/3/5336 5460677 4574162 C01685 HMDB00867 ribose Carbohydrate Pentose Metabolism 1471 LC/MS Polar 914 1508.2 195.05103 50-69-1 5779 4470639 C00121 HMDB00283 ribulonate/xylulonate/lyxonate* Carbohydrate Pentose Metabolism 61858 LC/MS Polar 100019968 2350 165.04046 ribulose/xylulose Carbohydrate Pentose Metabolism 54671 LC/MS Polar 100006122 1400 195.05102 5289590 S-methylcysteine Amino Acid Methionine, Cysteine, SAM and Taurine Metabolism 39592 LC/MS Polar 100002749 1942 134.02812 1187-84-4 24417 22826 HMDB02108 salicylate Xenobiotics Drug - Topical Agents 1515 LC/MS Polar 501 802 137.02422 69-72-7 338 331 C00805 HMDB01895 sedoheptulose Carbohydrate Pentose Metabolism 53237 LC/MS Polar 100002619 2255 209.06667 3019-74-7 5459879 4573620 HMDB03219 sphingosine 1-phosphate Lipid Sphingosines 34445 LC/MS Polar 100000626 1850 378.24148 26993-30-6 5283560 4446673 C06124 HMDB00277 succinate Energy TCA Cycle 1437 LC/MS Polar 252 3149 117.01933 110-15-6 1110 1078 C00042 HMDB00254 sucrose Carbohydrate Disaccharides and Oligosaccharides 1519 LC/MS Polar 935 3092 387.11442 57-50-1 5988 5768 C00089 HMDB00258 taurine Amino Acid Methionine, Cysteine, SAM and Taurine Metabolism 2125 LC/MS Polar 512 2120 124.00739 107-35-7 1123 1091 C00245 HMDB00251 threonate Cofactors and Vitamins Ascorbate and Aldarate Metabolism 27738 LC/MS Polar 100001022 2384 135.02989 70753-61-6 151152 133224 C01620 HMDB00943 tricarballylate Energy TCA Cycle 15729 LC/MS Polar 2053 4200 175.02481 99-14-9 14925 14220 C19806 HMDB31193 xylose Carbohydrate Pentose Metabolism 15581 LC/MS Polar 826 1727 195.05103 609-06-3 135191 85957 C00181 HMDB00098 METABOLITES_END #END