#METABOLOMICS WORKBENCH araskind_20190723_141420 DATATRACK_ID:1778 STUDY_ID:ST001230 ANALYSIS_ID:AN002043 PROJECT_ID:PR000823 VERSION 1 CREATED_ON August 1, 2019, 3:33 pm #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-VI) 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 S00031763 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10001 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021804 S00031764 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10002 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021805 S00031765 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10003 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021806 S00031766 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10004 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021807 S00031767 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10005 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021808 S00031768 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10006 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021809 S00031769 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10007 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021810 S00031770 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10008 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021811 S00031771 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10009 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021812 S00031772 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10010 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021813 S00031773 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10011 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021814 S00031774 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10012 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021815 S00031775 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10013 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021816 S00031776 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10014 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021817 S00031777 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10015 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021818 S00031778 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10016 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021819 S00031779 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10017 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021820 S00031780 Time Point:Baseline Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10018 Visit 2 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021803 S00031781 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10001 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021804 S00031782 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10002 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021805 S00031783 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10003 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021806 S00031784 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10004 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021807 S00031785 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10005 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021808 S00031786 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10006 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021809 S00031787 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10007 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021810 S00031788 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10008 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021811 S00031789 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10009 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021812 S00031790 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10010 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021813 S00031791 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10011 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021814 S00031792 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10012 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021815 S00031793 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10013 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021816 S00031794 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10014 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021817 S00031795 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10015 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021818 S00031796 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10016 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021819 S00031797 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10017 Visit 3 Stool NA#7 SUBJECT_SAMPLE_FACTORS SU0021820 S00031798 Time Point:Day 90 Sample type=Sample; Biological material=Feces; 10001 Visit 2 Stool NA#7=10018 Visit 3 Stool NA#7 #COLLECTION CO:COLLECTION_SUMMARY NA CO:SAMPLE_TYPE Feces #TREATMENT TR:TREATMENT_SUMMARY NA #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 pmol/mg MS_METABOLITE_DATA_START Samples S00031763 S00031764 S00031765 S00031766 S00031767 S00031768 S00031769 S00031770 S00031771 S00031772 S00031773 S00031774 S00031775 S00031776 S00031777 S00031778 S00031779 S00031780 S00031781 S00031782 S00031783 S00031784 S00031785 S00031786 S00031787 S00031788 S00031789 S00031790 S00031791 S00031792 S00031793 S00031794 S00031795 S00031796 S00031797 S00031798 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 3a,7a,12a-trihydroxycholestanoic acid 0.108 2.237 0.081 0.224 0.085 0.172 0.117 0.089 0.069 0.173 0.057 0.121 0.122 0.077 0.059 0.076 0.062 0.125 0.243 0.082 0.080 0.127 0.113 0.122 0.089 0.081 Chenodeoxycholic acidDeoxycholic acid 49.123 194.685 201.445 135.054 65.351 161.551 217.176 175.000 99.376 224.952 94.311 55.679 269.803 60.238 198.564 136.856 82.638 118.768 129.122 139.113 172.600 318.307 15.387 128.411 153.207 222.696 212.039 136.037 38.844 116.913 201.642 129.464 181.203 174.002 34.548 185.890 Cholic acid 0.414 3.428 388.175 166.891 0.854 1.425 3.106 5.228 3.708 13.033 0.581 1.672 7.670 14.269 1.177 6.624 0.987 14.229 2.401 3.454 7.969 307.936 3.701 4.225 3.015 9.088 7.910 2.803 0.036 2.219 10.522 17.684 12.517 20.737 0.562 8.193 Glychocholic acid 0.125 0.274 1.939 0.294 0.603 0.137 2.126 1.980 0.417 0.375 0.472 0.436 1.108 0.682 8.954 0.580 0.420 0.610 0.960 3.592 0.725 0.121 1.281 1.165 0.158 0.917 0.217 1.517 0.455 0.747 0.383 Glycochenodeoxycholic acid 0.331 0.585 1.229 0.547 0.193 1.379 1.887 0.269 12.423 3.072 1.004 0.518 0.920 1.414 0.093 1.708 1.199 16.722 1.176 1.403 1.259 1.897 3.628 3.367 0.497 3.769 1.850 0.286 1.709 0.771 6.548 1.453 2.068 1.040 Glycodeoxycholic acid 0.448 0.295 0.180 0.366 1.268 1.032 1.071 4.183 10.536 3.978 0.752 3.694 0.777 0.346 1.464 0.930 11.458 1.881 0.550 0.262 0.779 3.769 2.566 1.987 3.858 4.168 0.359 5.986 0.618 7.978 0.879 0.263 1.468 Glycohyodeoxycholic acid 2.219 0.081 0.173 Glycoursodeoxycholic acid 0.056 0.201 0.066 0.115 0.315 0.494 0.178 1.883 0.070 0.138 0.154 0.491 0.756 0.121 0.132 0.079 0.566 0.201 0.106 0.194 0.074 0.191 1.086 0.081 Hyodeoxycholic acid 3.839 155.579 1.498 1.045 23.384 47.452 344.502 165.110 36.658 349.016 14.071 59.115 2.762 45.902 93.789 76.534 26.978 48.006 141.958 106.176 42.660 3.323 0.649 86.260 104.085 525.021 90.009 252.376 13.309 49.757 30.657 39.906 33.689 38.575 14.382 214.263 Tauro-alpha-muricholic acidTauro-beta-muricholic acid 0.052 0.338 150.097 0.079 0.083 0.535 0.124 0.206 0.120 0.245 0.066 0.078 0.116 0.168 0.056 1.950 13.131 0.107 0.103 0.104 1.017 0.096 0.081 2.881 1.123 0.159 0.081 0.138 Taurochenodeoxycholic acid 0.168 0.351 4.134 0.146 0.117 0.467 0.325 0.125 0.895 0.423 0.077 0.196 0.312 1.139 0.050 0.426 1.199 5.488 0.493 0.319 0.207 0.290 1.872 0.554 0.170 0.379 0.213 0.172 0.259 0.313 0.759 0.312 1.560 0.248 Taurocholic acid 0.123 0.218 59.096 0.096 0.152 0.333 0.231 0.164 0.512 0.307 0.100 0.148 0.170 0.420 0.060 0.216 0.771 3.816 0.320 0.341 0.884 0.157 0.075 1.596 0.174 0.159 0.301 0.125 0.041 0.202 0.272 0.346 0.239 0.136 0.469 0.200 Taurodeoxycholic acid 0.185 0.141 0.358 0.058 0.132 0.336 0.228 0.176 3.914 0.835 0.073 0.181 0.483 0.523 0.050 0.140 0.439 1.662 0.435 1.705 5.564 0.079 1.113 0.169 0.277 10.690 0.245 0.193 0.328 1.054 0.443 0.131 0.129 0.314 Taurolithocolic acid 0.167 0.604 0.138 0.203 0.474 0.146 0.854 0.521 Tauroursodeoxycholic acid/Tauro-hyodeoxycholic acid 0.054 0.133 0.158 0.057 0.081 0.256 0.078 0.085 0.095 0.062 0.073 0.080 0.054 0.101 0.121 0.059 0.116 0.064 0.070 0.051 0.110 0.126 0.082 0.072 0.102 0.054 0.109 0.077 Ursodeoxycholic acid 0.845 7.610 8.400 10.262 6.684 5.051 1.316 1.428 33.326 1.278 46.423 7.819 83.587 1.741 12.698 3.481 5.475 126.050 3.739 3.318 a-Muricholic acid 0.453 3.067 619.201 268.734 0.656 0.573 3.236 4.229 34.992 3.017 1.115 0.898 48.962 28.713 0.827 97.821 0.606 27.110 1.639 5.464 19.397 610.073 2.135 0.981 1.405 10.760 57.936 1.202 0.593 1.065 58.943 103.059 18.403 99.697 0.416 1.229 b-Muricholic acid 0.214 1.013 51.833 27.470 0.182 0.443 2.270 2.704 0.759 3.169 0.743 1.010 1.979 0.521 1.646 0.488 1.475 1.858 0.667 66.384 0.142 0.626 1.316 3.862 1.422 1.302 0.715 0.855 1.112 2.583 0.556 1.266 0.371 1.220 g-Muricholic acid (hyocholic acid) 3.247 4.018 0.910 0.803 1.489 1.266 24.573 14.763 3.998 73.087 26.791 18.600 38.031 5.907 99.613 3.035 1.865 7.787 68.000 15.418 0.850 1.068 3.548 4.566 28.966 11.939 64.014 15.710 19.615 31.649 5.577 52.727 3.391 0.398 47.985 w-Muricholic acid 0.330 3.208 725.026 314.235 0.408 0.348 3.438 4.649 39.119 3.201 1.843 0.775 57.220 28.900 0.793 106.284 0.506 28.935 1.682 5.880 21.252 664.410 2.221 0.995 1.344 12.349 62.960 1.156 0.326 0.982 65.398 115.780 21.693 110.042 0.261 1.082 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name PubChem ID other_id other_id_type 3a,7a,12a-trihydroxycholestanoic acid 122312 THCA UM_Target_ID Chenodeoxycholic acidDeoxycholic acid 6742 CDCADCA UM_Target_ID Cholic acid 221493 CA UM_Target_ID Glychocholic acid 10140 GCA 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 Hyodeoxycholic acid 16219478 HDCA UM_Target_ID Tauro-alpha-muricholic acidTauro-beta-muricholic acid 168408 TaMCATbMCA UM_Target_ID Taurochenodeoxycholic acid 54608447 TCDCA UM_Target_ID Taurocholic acid 6675 TCA UM_Target_ID Taurodeoxycholic acid 10594 TDCA UM_Target_ID Taurolithocolic acid 10595 TLCA UM_Target_ID Tauroursodeoxycholic acid/Tauro-hyodeoxycholic acid 9848818 THDCATUDCa UM_Target_ID Ursodeoxycholic acid 54285959 UDCA UM_Target_ID a-Muricholic acid 53477700 aMCA UM_Target_ID b-Muricholic acid 5283853 bMCA UM_Target_ID g-Muricholic acid (hyocholic acid) 92805 HCA UM_Target_ID w-Muricholic acid 5283851 wMCA UM_Target_ID METABOLITES_END #END