#METABOLOMICS WORKBENCH Jason_20220518_225010 DATATRACK_ID:3260 STUDY_ID:ST002193 ANALYSIS_ID:AN003590 PROJECT_ID:PR001397 VERSION 1 CREATED_ON June 9, 2022, 3:08 am #PROJECT PR:PROJECT_TITLE The effects of obesity microbiota on colorectal carcinogenesis in murine models PR:PROJECT_SUMMARY Obesity is a risk factor for colorectal cancer (CRC). We aim to study the PR:PROJECT_SUMMARY effects and mechanisms of gut microbiota of obese subjects in contributing to PR:PROJECT_SUMMARY CRC progression. Conventional AOM-treated and ApcMin/+ mice receiving feces from PR:PROJECT_SUMMARY obese individuals showed significantly increased colon tumor formation compared PR:PROJECT_SUMMARY with those receiving feces from control subjects. AOM-treated mice receiving PR:PROJECT_SUMMARY feces from obese (OB-M) exhibited microbiota dysbiosis with enriched potential PR:PROJECT_SUMMARY pathobionts Erysipelotrichaceae bacterium GAM147, Turicibacter sp. H121, PR:PROJECT_SUMMARY Mucinivorans hirudinis, and depleted symbionts Bacteroides vulgatus, PR:PROJECT_SUMMARY Faecalibaculum rodentium, Bifidobacterium spp. and Lactobacillus delbrueckii. PR:PROJECT_SUMMARY The OB-M group also showed altered gut metabolites including elevated PR:PROJECT_SUMMARY phenylacetic acid, and depleted genipin. Moreover, OB-M group showed impaired PR:PROJECT_SUMMARY intestinal barrier function and significant upregulation of pro-inflammatory PR:PROJECT_SUMMARY cytokines and activation of oncogenic Wnt signaling pathway. In conclusion, gut PR:PROJECT_SUMMARY microbiota from obese individuals promotes colorectal carcinogenesis. Microbiota PR:PROJECT_SUMMARY modulation in obese individuals may provide new insight into obesity-driven CRC PR:PROJECT_SUMMARY prevention and therapy. PR:INSTITUTE The Chinese University of Hong Kong PR:DEPARTMENT Medicine and theraputics PR:LAST_NAME Kang PR:FIRST_NAME Xing PR:ADDRESS Rm806, Li Ka Shing Medical Science Building, PWH, Shatin, Hong Kong PR:EMAIL kangxing92@163.com PR:PHONE 93760832 #STUDY ST:STUDY_TITLE The effects of obesity microbiota produced metabolites on colorectal ST:STUDY_TITLE carcinogenesis in murine models ST:STUDY_SUMMARY Obesity is a risk factor for colorectal cancer (CRC). We aim to study the ST:STUDY_SUMMARY effects and mechanisms of gut microbiota of obese subjects in contributing to ST:STUDY_SUMMARY CRC progression. Conventional AOM-treated and ApcMin/+ mice receiving feces from ST:STUDY_SUMMARY obese individuals showed significantly increased colon tumor formation compared ST:STUDY_SUMMARY with those receiving feces from control subjects. AOM-treated mice receiving ST:STUDY_SUMMARY feces from obese (OB-M) exhibited microbiota dysbiosis with enriched potential ST:STUDY_SUMMARY pathobionts Erysipelotrichaceae bacterium GAM147, Turicibacter sp. H121, ST:STUDY_SUMMARY Mucinivorans hirudinis, and depleted symbionts Bacteroides vulgatus, ST:STUDY_SUMMARY Faecalibaculum rodentium, Bifidobacterium spp. and Lactobacillus delbrueckii. ST:STUDY_SUMMARY The OB-M group also showed altered gut metabolites including elevated ST:STUDY_SUMMARY phenylacetic acid, and depleted genipin. Moreover, OB-M group showed impaired ST:STUDY_SUMMARY intestinal barrier function and significant upregulation of pro-inflammatory ST:STUDY_SUMMARY cytokines and activation of oncogenic Wnt signaling pathway. In conclusion, gut ST:STUDY_SUMMARY microbiota from obese individuals promotes colorectal carcinogenesis. Microbiota ST:STUDY_SUMMARY modulation in obese individuals may provide new insight into obesity-driven CRC ST:STUDY_SUMMARY prevention and therapy. ST:INSTITUTE The Chinese University of Hong Kong ST:LAST_NAME Kang ST:FIRST_NAME Xing ST:ADDRESS Rm806, Li Ka Shing Medical Science Building, PWH, Shatin, Hong Kong ST:EMAIL kangxing92@163.com ST:PHONE 93760832 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS - NEG_2162 Treatment:LN-M RAW_FILE_NAME=NEG_2162.mzXML SUBJECT_SAMPLE_FACTORS - NEG_2164 Treatment:OB-M RAW_FILE_NAME=NEG_2164.mzXML SUBJECT_SAMPLE_FACTORS - NEG_2172 Treatment:LN-M RAW_FILE_NAME=NEG_2172.mzXML SUBJECT_SAMPLE_FACTORS - NEG_2177 Treatment:OB-M RAW_FILE_NAME=NEG_2177.mzXML SUBJECT_SAMPLE_FACTORS - NEG_2178 Treatment:LN-M RAW_FILE_NAME=NEG_2178.mzXML SUBJECT_SAMPLE_FACTORS - NEG_2179 Treatment:LN-M RAW_FILE_NAME=NEG_2179.mzXML SUBJECT_SAMPLE_FACTORS - NEG_2181 Treatment:OB-M RAW_FILE_NAME=NEG_2181.mzXML SUBJECT_SAMPLE_FACTORS - NEG_2187 Treatment:OB-M RAW_FILE_NAME=NEG_2187.mzXML SUBJECT_SAMPLE_FACTORS - NEG_2193 Treatment:LN-M RAW_FILE_NAME=NEG_2193.mzXML SUBJECT_SAMPLE_FACTORS - NEG_2195 Treatment:OB-M RAW_FILE_NAME=NEG_2195.mzXML SUBJECT_SAMPLE_FACTORS - POS_2162 Treatment:LN-M RAW_FILE_NAME=POS_2162.mzXML SUBJECT_SAMPLE_FACTORS - POS_2164 Treatment:OB-M RAW_FILE_NAME=POS_2164.mzXML SUBJECT_SAMPLE_FACTORS - POS_2172 Treatment:LN-M RAW_FILE_NAME=POS_2172.mzXML SUBJECT_SAMPLE_FACTORS - POS_2177 Treatment:OB-M RAW_FILE_NAME=POS_2177.mzXML SUBJECT_SAMPLE_FACTORS - POS_2178 Treatment:LN-M RAW_FILE_NAME=POS_2178.mzXML SUBJECT_SAMPLE_FACTORS - POS_2179 Treatment:LN-M RAW_FILE_NAME=POS_2179.mzXML SUBJECT_SAMPLE_FACTORS - POS_2181 Treatment:OB-M RAW_FILE_NAME=POS_2181.mzXML SUBJECT_SAMPLE_FACTORS - POS_2187 Treatment:OB-M RAW_FILE_NAME=POS_2187.mzXML SUBJECT_SAMPLE_FACTORS - POS_2193 Treatment:LN-M RAW_FILE_NAME=POS_2193.mzXML SUBJECT_SAMPLE_FACTORS - POS_2195 Treatment:OB-M RAW_FILE_NAME=POS_2195.mzXML #COLLECTION CO:COLLECTION_SUMMARY Mice stool samples were snap frozen in liquid nitrogen and kept at −80°C CO:COLLECTION_SUMMARY until further use CO:SAMPLE_TYPE Feces #TREATMENT TR:TREATMENT_SUMMARY AOM-induced mice were treated with feces from normal BMI and obese individuals. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 25 mg of each fecal sample from AOM-induced mice was added into 500 μL extract SP:SAMPLEPREP_SUMMARY solution (methanol: acetonitrile: water = 2:2:1) and homogenized. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Q Exactive HF-X CH:COLUMN_NAME UPLC BEH Amide column (2.1mm × 100mm, 1.7μm) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive HF-X Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS After centrifuge at 12000 rpm for 15 min at 4℃, the supernatant was MS:MS_COMMENTS transferred to an UHPLC system (Vanquish, Thermo Fisher Scientific) with a UPLC MS:MS_COMMENTS BEH Amide column (2.1mm × 100mm, 1.7μm) coupled to Q Exactive HFX mass MS:MS_COMMENTS spectrometer (Orbitrap MS, Thermo) for LC-MS/MS analyses. The mass spectrometer MS:MS_COMMENTS was operated on information dependent acquisition (IDA) mode in the control of MS:MS_COMMENTS the acquisition software (Xcalibur, Thermo). Raw data was converted to mzXML MS:MS_COMMENTS format using ProteoWizard and processed with an in-house program, which was MS:MS_COMMENTS developed using R and based on XCMS, for peak detection, extraction, alignment, MS:MS_COMMENTS and integration. MS:MS_RESULTS_FILE ST002193_AN003590_Results.txt UNITS:m/z Has m/z:Yes Has RT:Yes RT units:Seconds #END