#METABOLOMICS WORKBENCH araskind_20190723_141708 DATATRACK_ID:1779 STUDY_ID:ST001226 ANALYSIS_ID:AN002039 PROJECT_ID:PR000823 VERSION 1 CREATED_ON July 31, 2019, 9:37 am #PROJECT PR:PROJECT_TITLE Aquamin and Prevention of Colon Cancer PR:PROJECT_TYPE MS analysis PR:PROJECT_SUMMARY Effects of calcium and multi-mineral supplementation on gut microbes and PR:PROJECT_SUMMARY microbially-derived metabolites in patients at risk for colon cancer PR:INSTITUTE University of Michigan PR:DEPARTMENT Pathology PR:LABORATORY Aslam Lab PR:LAST_NAME Aslam PR:FIRST_NAME Muhammad Nadeem PR:ADDRESS Ann Arbor, MI PR:EMAIL mnaslam@umich.edu PR:PHONE 734-936-1897 #STUDY ST:STUDY_TITLE Aquamin and Prevention of Colon Cancer (part-II) ST:STUDY_TYPE MS analysis ST:STUDY_SUMMARY We propose to evaluate microbial and metabolic profiles in baseline and endpoint ST:STUDY_SUMMARY colonic mucosal, fecal, and serum samples from human patients at risk for CRC ST:STUDY_SUMMARY and enrolled in a 90-day phase I clinical trial. Patients will receive daily ST:STUDY_SUMMARY supplementation with calcium alone, a calcium-rich multimineral (Aquamin?), or ST:STUDY_SUMMARY placebo (maltodextrin) (n=10 per group). We hypothesize that dietary ST:STUDY_SUMMARY supplementation will correlate with CRC-protective metabolic profiles and that ST:STUDY_SUMMARY multimineral supplementation will generate more favorable profiles than calcium ST:STUDY_SUMMARY supplementation alone. ST:INSTITUTE University of Michigan ST:DEPARTMENT Biomedical Research Core Facilities ST:LABORATORY Metabolomics core ST:LAST_NAME Kachman ST:FIRST_NAME Maureen ST:ADDRESS Ann Arbor, MI ST:EMAIL mkachman@med.umich.edu ST:PHONE 734-232-0842 ST:NUM_GROUPS 24 ST:TOTAL_SUBJECTS 18 ST:STUDY_COMMENTS Colorectal cancer (CRC) is the third most common cancer and the second leading ST:STUDY_COMMENTS cause of cancer related death when both genders are combined. Epidemiologically, ST:STUDY_COMMENTS calcium intake has been protective against colonic adenomas and even colon ST:STUDY_COMMENTS cancer. Calcium supplementation has reduced the risk of colon adenoma formation ST:STUDY_COMMENTS in subjects with a history of previous colon polyps. The utility of calcium ST:STUDY_COMMENTS supplementation for colon cancer prevention is somewhat modulated by the modest ST:STUDY_COMMENTS or inconsistent level of protection afforded. Our preliminary data in mice and ST:STUDY_COMMENTS human enterocyte models shows that dietary supplementation with a multimineral ST:STUDY_COMMENTS supplement (Aquamin?) containing calcium in combination with 72 measureable ST:STUDY_COMMENTS trace minerals is more protective against tumors and epithelial growth ST:STUDY_COMMENTS dysregulation than calcium alone. One potential mechanism, supported by our ST:STUDY_COMMENTS rodent data, is that multimineral supplementation alters gut microbial ST:STUDY_COMMENTS populations to generate bile acid and short chain fatty acid (SCFA) profiles ST:STUDY_COMMENTS that are CRC-protective. #SUBJECT SU:SUBJECT_TYPE HUMAN SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS SU0021803 S00031799 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10001 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021804 S00031800 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10002 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021805 S00031801 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10003 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021806 S00031802 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10004 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021807 S00031803 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10005 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021808 S00031804 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10006 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021809 S00031805 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10007 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021810 S00031806 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10008 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021811 S00031807 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10009 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021812 S00031808 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10010 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021813 S00031809 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10011 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021814 S00031810 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10012 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021815 S00031811 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10013 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021816 S00031812 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10014 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021817 S00031813 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10015 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021818 S00031814 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10016 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021819 S00031815 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10017 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021820 S00031816 Time Point:Baseline Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10018 Visit 2 Serum SUBJECT_SAMPLE_FACTORS SU0021803 S00031817 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10001 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021804 S00031818 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10002 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021805 S00031819 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10003 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021806 S00031820 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10004 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021807 S00031821 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10005 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021808 S00031822 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10006 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021809 S00031823 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10007 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021810 S00031824 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10008 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021811 S00031825 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10009 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021812 S00031826 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10010 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021813 S00031827 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10011 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021814 S00031828 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10012 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021815 S00031829 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10013 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021816 S00031830 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10014 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021817 S00031831 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10015 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021818 S00031832 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10016 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021819 S00031833 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10017 Visit 3 Serum SUBJECT_SAMPLE_FACTORS SU0021820 S00031834 Time Point:Day 90 Sample type=Sample; Biological material=Serum; 10001 Visit 2 Serum=10018 Visit 3 Serum #COLLECTION CO:COLLECTION_SUMMARY Not available. CO:SAMPLE_TYPE Blood (serum) #TREATMENT TR:TREATMENT_SUMMARY Not available. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Two-step solvent extraction. Supernatants are combined, dried, and re-suspended SP:SAMPLEPREP_SUMMARY for LCMS separation by RPLC and measurements by ESI- QQQ MRM methods. Analytes SP:SAMPLEPREP_SUMMARY are reported as uM, and CV's are generally <15%. SP:SAMPLEPREP_PROTOCOL_FILENAME Bile_acids_analysis.doc #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Agilent 1260 CH:COLUMN_NAME Waters Acquity BEH C18 (50 x 2mm, 1.7um) CH:METHODS_FILENAME 2014-07-30-Bile_acid-full-BEH-C18-I.m.zip #ANALYSIS AN:ANALYSIS_TYPE MS AN:ACQUISITION_PARAMETERS_FILE 2014-07-30-Bile_acid-full-BEH-C18-I.m.zip #MS MS:INSTRUMENT_NAME Agilent 6490 QQQ MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS NA #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS uM MS_METABOLITE_DATA_START Samples S00031799 S00031800 S00031801 S00031802 S00031803 S00031804 S00031805 S00031806 S00031807 S00031808 S00031809 S00031810 S00031811 S00031812 S00031813 S00031814 S00031815 S00031816 S00031817 S00031818 S00031819 S00031820 S00031821 S00031822 S00031823 S00031824 S00031825 S00031826 S00031827 S00031828 S00031829 S00031830 S00031831 S00031832 S00031833 S00031834 Factors Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Baseline Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Time Point:Day 90 Deoxycholic acid 12.705 161.704 95.581 68.824 118.139 7.835 134.651 254.679 178.766 442.837 139.513 397.229 505.035 110.143 258.185 30.135 52.372 40.849 137.926 278.345 216.741 199.116 88.616 80.481 108.468 115.291 341.005 249.200 108.294 155.575 374.801 83.774 349.912 251.324 0.000 178.789 Cholic acid 26.102 16.855 69.113 16.488 4.752 24.693 36.725 2.664 5.817 50.025 0.053 124.221 71.080 5.786 4.473 2.724 3.798 1.870 10.595 2.708 13.069 27.755 4.369 3.912 32.791 2.392 4.979 11.511 22.812 12.892 96.256 2.375 1.989 6.497 13.534 2.041 Glycochenodeoxycholic acid 62.306 409.758 754.036 314.296 28.646 48.268 21.062 21.181 35.186 23.007 13.677 34.664 36.201 92.264 58.096 101.711 30.208 332.449 80.993 503.813 389.712 69.278 22.770 23.853 34.612 22.523 70.264 41.401 17.046 30.689 110.245 80.905 253.719 447.152 12.929 38.345 Glycodeoxycholic acid 42.009 58.295 0.000 29.743 25.551 22.001 16.939 44.146 15.581 39.707 11.026 20.744 54.747 24.970 36.234 53.377 12.156 117.047 71.849 216.522 42.538 18.538 16.561 13.035 19.336 26.937 39.904 58.368 28.602 20.580 182.875 20.343 142.590 164.824 6.467 40.900 Glycohyodeoxycholic acid 0.000 0.000 0.000 0.000 5.577 3.624 3.776 5.442 0.000 3.314 0.000 0.000 3.250 0.000 3.317 0.000 0.000 0.000 3.593 0.000 3.799 3.586 5.483 3.235 3.813 0.000 0.000 3.134 5.673 0.000 0.000 0.000 0.000 0.000 0.000 3.254 Glycoursodeoxycholic acid 9.275 11.582 24.437 12.046 7.246 6.227 7.215 5.084 6.543 5.551 42.001 6.689 6.380 7.742 7.048 22.116 5.400 18.824 10.596 15.031 14.663 8.181 4.579 4.390 11.201 4.956 11.399 4.675 3.829 6.761 12.682 6.610 18.401 94.008 3.950 3.960 Glychocholic acid 27.075 54.276 179.788 32.622 7.113 10.129 6.960 9.825 7.273 10.500 8.571 8.352 10.633 11.922 9.501 14.667 11.007 30.462 21.804 85.452 71.274 22.285 7.062 10.520 10.604 7.716 12.757 14.259 10.633 8.739 33.515 12.432 27.187 76.175 6.888 15.516 Glycohyocholic acid 15.274 71.248 89.486 27.453 20.947 12.595 0.000 21.608 0.000 6.642 7.509 8.333 5.847 30.181 13.243 7.530 18.734 23.147 9.540 84.423 37.200 15.628 12.480 0.000 12.600 9.760 11.380 15.448 0.000 13.302 8.547 30.752 37.487 13.821 0.000 7.264 Taurolithocolic acid 3.974 4.251 3.941 4.242 5.004 7.724 4.039 3.973 4.079 4.567 4.096 3.950 3.929 4.065 3.982 4.471 4.082 4.658 4.446 4.932 4.217 3.954 4.325 4.654 4.530 4.088 3.971 4.028 3.847 4.075 4.158 4.199 6.171 4.659 4.328 4.205 Tauroursodeoxycholic acid 11.228 10.963 11.118 11.056 11.140 11.469 11.032 11.005 10.984 11.080 10.937 10.922 10.994 10.925 11.470 10.911 11.188 10.958 11.250 11.021 11.077 11.014 11.099 11.009 11.322 10.992 11.044 11.056 10.998 10.940 11.014 10.926 11.654 0.000 11.226 10.988 Taurochenodeoxycholic acid 20.840 86.517 55.156 26.251 7.980 11.247 10.442 8.051 8.518 7.651 6.807 7.404 8.224 12.737 7.452 13.189 13.643 44.277 22.720 95.593 16.555 10.442 8.768 9.800 9.277 7.784 10.079 7.552 6.830 8.380 14.250 8.913 19.527 45.042 9.826 9.787 Taurodeoxycholic acid 16.414 17.657 54.188 8.663 7.751 9.292 8.458 9.748 6.945 8.209 6.496 6.888 10.025 8.273 7.477 9.738 8.503 20.797 22.952 49.283 7.315 7.151 7.471 7.710 7.998 9.128 8.168 7.983 6.369 7.637 21.241 6.900 16.190 22.462 6.526 10.659 Tauro-hyodeoxycholic acid 6.062 6.132 6.056 5.882 6.178 5.903 6.026 5.981 5.795 5.826 5.812 5.819 5.802 5.860 0.000 5.954 5.881 6.116 6.035 6.282 5.843 5.821 6.228 5.804 5.993 5.826 5.875 5.805 5.901 5.805 5.937 5.817 5.934 7.513 5.821 5.795 Taurocholic acid 16.142 21.825 30.470 10.685 6.953 7.904 7.123 7.308 6.826 7.127 6.934 6.921 7.650 7.438 7.171 8.098 8.301 13.673 16.284 24.361 12.922 8.895 6.693 7.754 7.394 7.263 7.059 7.357 6.931 7.141 10.990 7.003 8.804 17.959 7.509 9.210 Tauro-alpha-muricholic acidTauro-beta-muricholic acid 11.751 14.283 9.596 10.494 17.233 9.974 10.012 39.157 8.972 10.344 9.112 10.768 10.929 10.931 10.695 10.486 16.474 11.780 14.266 24.551 9.420 9.329 12.408 11.464 15.910 29.546 9.135 13.667 9.755 10.842 12.204 10.025 11.329 11.224 9.577 10.135 3a,7a,12a-trihydroxycholestanoic acid 7.760 23.955 9.688 7.878 8.048 6.955 7.020 7.478 6.318 6.561 6.440 6.501 6.654 8.404 0.000 6.400 14.176 9.308 8.149 27.130 7.029 6.970 7.210 8.158 8.316 6.836 6.305 6.747 0.000 7.078 7.151 7.639 8.844 7.161 11.120 6.873 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name PubChem ID other_id other_id_type Deoxycholic acid 6742 DCACDCA UM_Target_ID Cholic acid 221493 CA UM_Target_ID Glycochenodeoxycholic acid 9548796 GCDCA UM_Target_ID Glycodeoxycholic acid 18602029 GDCA UM_Target_ID Glycohyodeoxycholic acid 114611 GHDCA UM_Target_ID Glycoursodeoxycholic acid 12310288 GUDCA UM_Target_ID Glychocholic acid 10140 GCA UM_Target_ID Glycohyocholic acid 13955647 GHCA UM_Target_ID Taurolithocolic acid 10595 TLCA UM_Target_ID Tauroursodeoxycholic acid 9848818 TUDCA UM_Target_ID Taurochenodeoxycholic acid 54608447 TCDCA UM_Target_ID Taurodeoxycholic acid 10594 TDCA UM_Target_ID Tauro-hyodeoxycholic acid 9848818 THDCA UM_Target_ID Taurocholic acid 6675 TCA UM_Target_ID Tauro-alpha-muricholic acidTauro-beta-muricholic acid 168408 TaMCATbMCA UM_Target_ID 3a,7a,12a-trihydroxycholestanoic acid 122312 THCA UM_Target_ID METABOLITES_END #END