#METABOLOMICS WORKBENCH araskind_20190723_133952 DATATRACK_ID:1777 STUDY_ID:ST001225 ANALYSIS_ID:AN002038 PROJECT_ID:PR000822 VERSION 1 CREATED_ON July 30, 2019, 5:54 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 Targeted metabolomics 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 S00031727 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10001 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021804 S00031728 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10002 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021805 S00031729 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10003 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021806 S00031730 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10004 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021807 S00031731 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10005 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021808 S00031732 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10006 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021809 S00031733 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10007 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021810 S00031734 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10008 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021811 S00031735 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10009 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021812 S00031736 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10010 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021813 S00031737 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10011 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021814 S00031738 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10012 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021815 S00031739 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10013 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021816 S00031740 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10014 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021817 S00031741 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10015 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021818 S00031742 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10016 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021819 S00031743 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10017 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021820 S00031744 Time Point:Baseline Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10018 Visit 2 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021803 S00031745 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10001 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021804 S00031746 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10002 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021805 S00031747 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10003 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021806 S00031748 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10004 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021807 S00031749 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10005 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021808 S00031750 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10006 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021809 S00031751 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10007 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021810 S00031752 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10008 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021811 S00031753 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10009 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021812 S00031754 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10010 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021813 S00031755 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10011 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021814 S00031756 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10012 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021815 S00031757 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10013 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021816 S00031758 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10014 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021817 S00031759 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10015 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021818 S00031760 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10016 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021819 S00031761 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10017 Visit 3 Colon NA#2 SUBJECT_SAMPLE_FACTORS SU0021820 S00031762 Time Point:Day 90 Sample type=Sample; Biological material=Tissues; 10001 Visit 2 Colon NA#2=10018 Visit 3 Colon NA#2 #COLLECTION CO:COLLECTION_SUMMARY Colonic mucosal tissue CO:SAMPLE_TYPE Colon #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 #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 S00031727 S00031728 S00031729 S00031730 S00031731 S00031732 S00031733 S00031734 S00031735 S00031736 S00031737 S00031738 S00031739 S00031740 S00031741 S00031742 S00031743 S00031744 S00031745 S00031746 S00031747 S00031748 S00031749 S00031750 S00031751 S00031752 S00031753 S00031754 S00031755 S00031756 S00031757 S00031758 S00031759 S00031760 S00031761 S00031762 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 Cholic acid 0.167 0.348 11.591 19.376 0.176 0.151 0.347 0.283 0.335 0.223 0.095 0.930 0.204 0.251 0.183 0.088 0.306 0.347 0.198 0.227 1.413 12.052 0.385 0.475 0.327 0.214 0.199 0.140 0.118 0.251 0.198 0.276 0.344 0.178 0.184 0.135 g-Muricholic acid (hyocholic acid) 0.101 0.195 0.210 0.106 0.151 0.159 0.152 0.061 0.353 0.107 0.091 0.134 0.158 0.099 0.158 0.111 0.137 0.226 0.123 0.147 0.166 0.147 0.104 0.099 0.308 0.273 0.188 0.125 0.145 0.133 0.134 w-Muricholic acid 0.123 0.199 0.211 0.135 0.119 0.123 0.162 0.124 0.178 0.141 0.068 0.476 0.111 0.125 0.149 0.078 0.121 0.131 0.144 0.163 0.223 0.146 0.208 0.304 0.155 0.160 0.112 0.128 0.124 0.240 0.133 0.121 0.163 0.135 0.130 0.104 Deoxycholic acid 3.851 99.200 53.408 58.099 35.201 11.200 41.547 80.055 25.736 44.581 13.094 150.542 8.533 15.603 39.864 18.073 3.714 31.639 19.092 18.524 131.321 36.420 18.859 61.143 13.454 29.145 34.742 10.301 17.831 182.237 24.204 29.563 34.135 12.553 7.627 10.357 Hyodeoxycholic acid 1.142 8.771 2.767 6.363 10.868 10.228 11.473 8.092 7.890 10.878 3.775 31.521 1.725 5.048 10.102 3.560 2.437 7.530 3.899 6.529 12.143 6.668 4.280 6.361 3.761 5.944 2.730 5.576 10.029 24.226 3.645 1.396 3.271 2.764 1.426 3.254 Glycochenodeoxycholic acid 0.219 0.202 0.690 0.314 0.128 0.169 0.161 0.129 0.289 0.163 0.065 0.468 0.108 0.174 0.147 0.085 0.130 0.239 0.140 0.191 0.564 0.249 0.209 0.283 0.166 0.141 0.157 0.129 0.109 0.231 0.141 0.146 0.199 0.217 0.119 0.142 Glycodeoxycholic acid 0.195 0.279 0.249 0.322 0.134 0.166 0.212 0.148 0.270 0.691 0.084 0.490 0.156 0.129 0.180 0.157 0.130 0.232 0.181 0.212 0.554 0.289 0.226 0.306 0.202 0.202 0.150 0.180 0.137 0.270 0.278 0.218 0.257 0.202 0.119 0.156 Glycohyodeoxycholic acid 0.120 0.162 0.220 0.108 0.118 0.116 0.144 0.125 0.176 0.133 0.064 0.440 0.093 0.111 0.144 0.063 0.111 0.123 0.133 0.144 0.210 0.107 0.000 0.288 0.152 0.138 0.000 0.120 0.108 0.248 0.106 0.104 0.145 0.123 0.109 0.095 Glycoursodeoxycholic acid 0.129 0.162 0.232 0.119 0.117 0.120 0.148 0.125 0.181 0.131 0.078 0.446 0.096 0.115 0.144 0.069 0.113 0.130 0.135 0.144 0.218 0.114 0.209 0.291 0.154 0.139 0.115 0.119 0.108 0.246 0.112 0.107 0.153 0.148 0.111 0.097 Glychocholic acid 0.094 0.131 0.288 0.332 0.088 0.112 0.114 0.155 0.113 0.050 0.335 0.104 0.096 0.107 0.067 0.085 0.151 0.125 0.120 0.346 0.151 0.159 0.122 0.110 0.107 0.096 0.093 0.284 0.107 0.084 0.137 0.120 0.094 0.126 Taurocholic acid 0.145 0.169 0.555 0.173 0.142 0.119 0.155 0.136 0.184 0.134 0.066 0.462 0.097 0.117 0.148 0.068 0.118 0.141 0.141 0.148 0.304 0.132 0.216 0.298 0.158 0.142 0.114 0.121 0.112 0.229 0.110 0.110 0.150 0.129 0.115 0.100 Tauro-alpha-muricholic acidTauro-beta-muricholic acid 0.133 0.159 1.017 0.152 0.113 0.113 0.146 0.120 0.177 0.128 0.063 0.469 0.093 0.114 0.145 0.078 0.114 0.125 0.133 0.142 0.497 0.127 0.200 0.286 0.149 0.136 0.119 0.116 0.105 0.223 0.106 0.113 0.144 0.120 0.107 0.094 3a,7a,12a-trihydroxycholestanoic acid 0.132 0.167 0.240 0.113 0.122 0.120 0.149 0.131 0.182 0.137 0.068 0.464 0.099 0.119 0.147 0.067 0.119 0.131 0.141 0.149 0.221 0.111 0.223 0.306 0.159 0.146 0.114 0.124 0.115 0.240 0.112 0.110 0.151 0.128 0.114 0.100 Taurochenodeoxycholic acid 1.878 1.116 1.014 0.267 0.239 0.165 0.218 0.187 0.233 0.169 0.084 0.577 0.121 0.148 0.187 0.083 0.148 0.176 0.179 0.188 0.296 0.158 0.288 0.396 0.199 0.181 0.144 0.151 0.136 0.292 0.135 0.136 0.190 0.163 0.150 0.125 Taurodeoxycholic acid 1.647 0.987 0.842 0.266 0.217 0.160 0.212 0.184 0.235 0.223 0.100 0.623 0.126 0.146 0.190 0.099 0.155 0.176 0.177 0.188 0.476 0.204 0.340 0.431 0.206 0.189 0.191 0.162 0.147 0.337 0.151 0.209 0.231 0.170 0.148 0.124 Tauro-hyodeoxycholic acidTauroursodeoxycholic acid 0.383 0.263 0.301 0.126 0.137 0.132 0.167 0.142 0.201 0.148 0.073 0.506 0.106 0.128 0.162 0.073 0.126 0.141 0.151 0.163 0.241 0.120 0.234 0.329 0.172 0.157 0.126 0.134 0.123 0.248 0.121 0.118 0.166 0.139 0.124 0.108 Taurolithocolic acid 12.181 15.473 22.135 6.896 7.225 3.359 8.106 12.348 4.329 3.781 3.166 17.090 2.376 2.264 2.903 1.069 1.952 2.030 2.019 1.723 3.273 0.852 1.943 2.978 1.232 1.244 1.002 0.440 0.652 5.846 0.429 0.517 0.700 0.390 0.567 0.299 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name pubchem_id other_id other_id_type Cholic acid 221493 CA UM_Target_ID g-Muricholic acid (hyocholic acid) 92805 HCA UM_Target_ID w-Muricholic acid 5283851 wMCA UM_Target_ID Deoxycholic acid 6742 DCA/CDCA UM_Target_ID Hyodeoxycholic acid 16219478 HDCA 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 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 Taurochenodeoxycholic acid 54608447 TCDCA UM_Target_ID Taurodeoxycholic acid 10594 TDCA UM_Target_ID Tauro-hyodeoxycholic acidTauroursodeoxycholic acid 9848818 THDCATUDCa UM_Target_ID Taurolithocolic acid 10595 TLCA UM_Target_ID METABOLITES_END #END