#METABOLOMICS WORKBENCH araskind_20170619_134053 DATATRACK_ID:1025 STUDY_ID:ST000723 ANALYSIS_ID:AN001133 PROJECT_ID:PR000520 VERSION 1 CREATED_ON July 2, 2017, 9:44 pm #PROJECT PR:PROJECT_TITLE Analysis of SCFA in the fecal matter of wt and Orai1kO mice PR:PROJECT_TYPE MS analysis PR:PROJECT_SUMMARY Orai1 mediated pancreatic secretion is critical for gut innate immunity PR:INSTITUTE National Institutes of Health PR:DEPARTMENT NIDCR/MPTB PR:LABORATORY Muallem Lab PR:LAST_NAME Muallem PR:FIRST_NAME Shmuel PR:ADDRESS Bethesda, Maryland PR:EMAIL 301-402-0262 PR:PHONE 301-471-3027 #STUDY ST:STUDY_TITLE Analysis of SCFA in the fecal matter of wt and Orai1kO mice ST:STUDY_TYPE MS analysis ST:STUDY_SUMMARY The gut microbiome participates in numerous physiological functions and is ST:STUDY_SUMMARY believed to be shaped by the host intestine. We report here an unsuspected ST:STUDY_SUMMARY prominent role of Orai1-mediated pancreatic acinar cell exocytosis in shaping ST:STUDY_SUMMARY the microbiome. Deletion of Orai1 in pancreatic acini of mature mice maintained ST:STUDY_SUMMARY on solid diet resulted in 60-70% mortality. The mice have severe bacterial ST:STUDY_SUMMARY burden with dysbiosis resulting in systemic inflammation and death. This occurs ST:STUDY_SUMMARY despite prominent Paneth cell hyperplasia and activation of the intestinal ST:STUDY_SUMMARY innate immune response. Secretion of and bacterial killing by pancreatic ST:STUDY_SUMMARY defensins are markedly reduced, resulting in microbiota with decreased diversity ST:STUDY_SUMMARY and increased pathogenic bacteria. Survival and weight gain are not rescued by ST:STUDY_SUMMARY digestive enzyme supplements, but are by broad-spectrum antibiotics and purified ST:STUDY_SUMMARY liquid diet. These findings reveal an unexpected profound role of pancreatic ST:STUDY_SUMMARY secretion in shaping the microbiome 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 6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714 ST:EMAIL mkachman@med.umich.edu ST:PHONE (734) 232-8175 ST:NUM_GROUPS 4 ST:TOTAL_SUBJECTS 4 #SUBJECT SU:SUBJECT_TYPE MOUSE SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS SU0016351 S00026161 Diet:solid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016351 S00026162 Diet:solid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016351 S00026163 Diet:solid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016351 S00026164 Diet:solid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016351 S00026165 Diet:solid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016351 S00026166 Diet:solid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016352 S00026167 Diet:solid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016352 S00026168 Diet:solid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016352 S00026169 Diet:solid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016352 S00026170 Diet:solid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016352 S00026171 Diet:solid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016352 S00026172 Diet:solid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016353 S00026173 Diet:liquid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016353 S00026174 Diet:liquid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016353 S00026175 Diet:liquid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016353 S00026176 Diet:liquid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016353 S00026177 Diet:liquid diet | Genotype:wt SUBJECT_SAMPLE_FACTORS SU0016354 S00026178 Diet:liquid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016354 S00026179 Diet:liquid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016354 S00026180 Diet:liquid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016354 S00026181 Diet:liquid diet | Genotype:Orai1Ko SUBJECT_SAMPLE_FACTORS SU0016354 S00026182 Diet:liquid diet | Genotype:Orai1Ko #COLLECTION CO:COLLECTION_SUMMARY - #TREATMENT TR:TREATMENT_SUMMARY - #SAMPLEPREP SP:SAMPLEPREP_SUMMARY - SP:SAMPLEPREP_PROTOCOL_FILENAME A007 - Short Chain Fatty Acids.pdf #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE GC CH:INSTRUMENT_NAME Agilent 7890N CH:COLUMN_NAME Phenomenex Zebron ZB-WAXplus (30m x 0.25mm, 0.25um) #ANALYSIS AN:ANALYSIS_TYPE MS AN:ANALYSIS_PROTOCOL_FILE A007 - Short Chain Fatty Acids.pdf #MS MS:MS_COMMENTS - MS:INSTRUMENT_NAME Agilent 5975 MS:INSTRUMENT_TYPE Single quadrupole MS:MS_TYPE EI MS:ION_MODE POSITIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS nmol/mg MS_METABOLITE_DATA_START Samples S00026161 S00026162 S00026163 S00026164 S00026165 S00026166 S00026167 S00026168 S00026169 S00026170 S00026171 S00026172 S00026173 S00026174 S00026175 S00026176 S00026177 S00026178 S00026179 S00026180 S00026181 S00026182 Factors Diet:solid diet | Genotype:wt Diet:solid diet | Genotype:wt Diet:solid diet | Genotype:wt Diet:solid diet | Genotype:wt Diet:solid diet | Genotype:wt Diet:solid diet | Genotype:wt Diet:solid diet | Genotype:Orai1Ko Diet:solid diet | Genotype:Orai1Ko Diet:solid diet | Genotype:Orai1Ko Diet:solid diet | Genotype:Orai1Ko Diet:solid diet | Genotype:Orai1Ko Diet:solid diet | Genotype:Orai1Ko Diet:liquid diet | Genotype:wt Diet:liquid diet | Genotype:wt Diet:liquid diet | Genotype:wt Diet:liquid diet | Genotype:wt Diet:liquid diet | Genotype:wt Diet:liquid diet | Genotype:Orai1Ko Diet:liquid diet | Genotype:Orai1Ko Diet:liquid diet | Genotype:Orai1Ko Diet:liquid diet | Genotype:Orai1Ko Diet:liquid diet | Genotype:Orai1Ko PROPIONIC ACID 1.615156677 .120879216 .157719691 .161925117 2.965777193 5.775169 1.227202435 8.77371213 3.946478607 18.47227042 4.429661368 2.767458011 13.19120058 15.21151317 4.070402499 3.84845463 .462052156 .222445701 .248348813 5.830192609 3.721005364 1.376790515 ISOVALERIC ACID .064493362 .010986445 .023504794 .012567707 .06529296 .385784746 .08086836 .10681403 .300419621 .275271163 .442667239 .104872294 .139236502 .152911405 .058519068 .151082874 .016554864 .034657274 .079720751 .108838746 .106320405 .063555533 ACETIC ACID 16.40414094 4.262160055 7.709832617 8.070304867 19.62127593 51.79918477 25.60147271 44.35590991 48.29855283 83.54730226 29.85394978 22.1757539 29.25736336 50.90112084 21.61696186 58.84903859 9.555935954 5.245336737 4.505737884 22.83657485 34.15362865 51.10347874 BUTYRIC ACID .335006594 .089664983 .130675687 .145410333 .716052017 2.183704594 1.152703113 .448122655 5.753952554 2.394097511 1.206296366 .576068665 2.848176812 6.393065734 .998813605 1.22465293 .224361801 .151125877 .199295184 .606789361 1.465439117 .453379103 OCTANOIC ACID .169584069 .09531197 .110085129 .174852109 .070423713 .125726365 .044831494 1.116176776 .080274359 .098552064 .048725328 .076644659 .04709738 .085221582 .080996302 .113957575 .348701913 .298632032 .127535794 .186201884 .103812494 .047868764 VALERIC ACID .018415489 .008549986 .027514256 .012674961 .049802526 .423881187 .509117544 .679166579 1.176309169 .476108656 .114174356 .183335442 .491840883 .841016157 .16267396 .863917649 .027088095 .016512258 .05043965 .147780316 .349393685 .107268261 HEPTANOIC ACID .002784989 .007682954 .011987142 .01223794 .006473325 .005097915 .003329668 .051823111 .005368976 .006198687 .007154884 .006878155 .004052787 .007074573 .005084526 .005293018 .018017711 .015826328 .018881454 .009731908 .005864849 .003897417 HEXANOIC ACID .016885939 .03035324 .040015973 .045508484 .025449152 .024103121 .049963556 6.594860469 .054403655 .038860853 .035060978 .035852375 .028953983 .039174386 .029955017 .050881827 .071827559 .053313874 .042050666 .034723561 .064165888 .043907126 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name moverz_quant ri ri_type pubchem_id inchi_key kegg_id other_id other_id_type PROPIONIC ACID 1032 ISOVALERIC ACID 10430 ACETIC ACID 176 BUTYRIC ACID 264 OCTANOIC ACID 379 VALERIC ACID 7991 HEPTANOIC ACID 8094 HEXANOIC ACID 8892 METABOLITES_END #END