#METABOLOMICS WORKBENCH araskind_20190724_064341 DATATRACK_ID:1781 STUDY_ID:ST001228 ANALYSIS_ID:AN002041 PROJECT_ID:PR000823 VERSION 1 CREATED_ON July 31, 2019, 9:54 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-IV) 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 Not available CO:SAMPLE_TYPE Feces #TREATMENT TR:TREATMENT_SUMMARY Not avaialble #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Cold extraction of short chain fatty acids, measured by EI- GCMS without SP:SAMPLEPREP_SUMMARY derivatization. SCFA species are reported as uM, with CV's generally ~10%. SP:SAMPLEPREP_PROTOCOL_FILENAME Short_chain_fatty_acids_analysis.doc #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE GC CH:INSTRUMENT_NAME Agilent 7890N CH:COLUMN_NAME Agilent HP5-MS (15m ? 0.25mm, 0.25 um) #ANALYSIS AN:ANALYSIS_TYPE MS AN:ANALYSIS_PROTOCOL_FILE Short_chain_fatty_acids_analysis.doc AN:ACQUISITION_PARAMETERS_FILE WAXPLUS_100-200C_3_SPLIT10-1_SIM.M.zip #MS MS:INSTRUMENT_NAME Agilent 5975 MS:INSTRUMENT_TYPE Single quadrupole MS:MS_TYPE EI MS:ION_MODE POSITIVE MS:MS_COMMENTS Not available. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS nmol/mg (wet weight) 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 Acetate 5.4128 23.1385 12.2052 83.5626 0.0087 15.6614 30.8313 11.4587 6.0536 21.0272 10.1695 21.3680 18.9944 18.0531 22.7094 38.0901 15.1582 27.2954 17.7829 0.0106 30.0469 53.2871 8.6838 15.4034 25.2398 10.1158 4.9019 24.8182 4.5074 27.1967 16.7970 22.2228 18.5868 24.0894 21.9800 18.6100 Propionate 0.6170 7.0777 4.0988 21.7521 0.0009 3.1991 6.9402 2.1778 2.1748 7.5323 2.9186 4.1497 7.0154 7.3179 1.6701 15.6751 3.7035 9.3318 1.6810 0.0044 17.6175 21.0259 0.4066 3.1809 4.2386 4.0719 1.2768 6.4869 2.0444 4.0876 8.2299 9.5327 1.9579 10.0401 7.8715 6.8353 Butyrate 0.1715 4.1226 1.0582 17.7859 0.0002 2.4345 5.4750 4.8318 0.7880 3.2596 0.9691 4.4336 4.1397 7.0103 5.4094 12.1693 1.5216 8.6785 2.2480 0.0017 9.0994 6.5229 0.0758 5.0778 3.2521 5.0577 0.3362 7.0281 1.0308 5.7901 3.8306 5.2358 1.9932 7.9955 4.3325 4.2279 Isovalerate 0.0320 0.3572 0.3497 0.7475 0.0001 0.3630 1.2773 0.8058 0.2550 0.8088 0.3412 0.3927 0.4352 0.3709 1.0064 2.0548 0.3376 0.9708 1.5039 0.0003 2.0204 0.4441 0.0114 0.8566 1.3429 0.4155 0.1191 0.3127 0.1703 0.5770 0.8177 0.2803 0.1707 0.3913 1.0426 0.8869 Valerate 0.0498 0.6899 0.6639 2.1159 0.0001 0.6993 1.4936 0.9186 0.1963 0.8322 0.4613 0.6111 0.9710 0.6588 1.3449 5.8437 0.4027 2.1096 1.3134 0.0005 4.0320 1.8023 0.0267 1.5819 1.4482 0.6373 0.1141 1.2716 0.1754 1.1564 1.0424 1.0788 0.7858 2.0369 1.1786 1.1322 Hexanoate 0.0695 0.6117 0.0423 0.3956 0.0001 0.3272 0.5840 0.5289 0.0298 0.2274 0.0415 0.6071 0.2617 0.0301 8.4846 0.0831 0.1304 1.2535 0.0931 0.0002 0.0459 0.1726 0.0332 0.7843 0.1912 0.6402 0.0464 0.8548 0.0380 1.0079 0.1306 0.0498 1.4536 0.0924 0.1975 0.5056 Heptanoate 0.0105 0.0811 0.0164 0.0127 0.0000 0.0586 0.1628 0.0682 0.0084 0.0408 0.0106 0.0521 0.0370 0.0070 2.5291 0.0073 0.0280 0.2003 0.0223 0.0000 0.0082 0.0103 0.0112 0.1430 0.0332 0.0167 0.0089 0.0853 0.0092 0.0952 0.0119 0.0056 0.3343 0.0064 0.0278 0.0776 Octanoate 0.8428 0.4805 0.3809 0.3044 0.0005 0.4159 1.0269 0.9325 0.2458 0.2948 0.3179 0.3485 0.3244 0.1624 26.1941 0.1737 0.4675 0.3652 0.1882 0.0004 0.1543 0.2067 0.2323 0.3713 0.6451 8.9502 0.3009 0.1196 0.0814 0.3019 0.0687 0.0622 0.7387 0.0428 0.2464 0.1233 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name PubChem ID Acetate 176 Propionate 1032 Butyrate 264 Isovalerate 10430 Valerate 7991 Hexanoate 8892 Heptanoate 8094 Octanoate 379 METABOLITES_END #END