Summary of Study ST004406

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002785. The data can be accessed directly via it's Project DOI: 10.21228/M8P25P This work is supported by NIH grant, U2C- DK119886.

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Study IDST004406
Study TitleEffects of a Complex Probiotic Intervention on Serum Metabolism and Tumor-Bearing Intestinal Segment Metabolism in FOLFOX Chemotherapy-Treated Mice with Colorectal Cancer
Study SummaryAn AOM/DSS-induced inflammation-associated colorectal cancer mouse model was established to investigate the metabolic changes in FOLFOX chemotherapy with and without combined probiotic intervention. For the azoxymethane plus dextran sulfate sodium (AOM/DSS) model, 8-week-old female BALB/c mice were intraperitoneally injected with 10 mg/kg AOM (Sigma-Aldrich, Saint Louis, USA), followed by three cycles of DSS (MP Biomedicals, Ohio, USA) to mimic colitis-associated colorectal cancer (CAC). For each cycle, the mice were given free access to drinking water supplemented with 2% DSS for 1 week, followed by 2 weeks of regular water. FOLFOX treatment was used as described in 10.3390/nu15051117. Following a one-week intervention with composite probiotics or vehicle, oxaliplatin (1 mg/kg) was administered intraperitoneally, followed by daily intraperitoneal injections of 5-fluorouracil (50 mg/kg) and calcium folinate (10 mg/kg) for 5 days. All solutions were freshly prepared in sterile saline before administration. The control group received an equivalent volume of saline via intraperitoneal injection. On the day of oxaliplatin injection, loperamide (0.2 mg/day) was administered via oral gavage to the designated mice, according to the experimental protocol.The tissue and serum samples for this test were collected one day after completion of the FOLFOX regimen. Compared with the CAC-F group, the CAC-FPL group displayed 62 upregulated and 36 downregulated metabolites in tumor tissues, along with 181 upregulated and 149 downregulated serum metabolites. Pathway analysis revealed significant enrichment of nicotinate and nicotinamide metabolism, suggesting that nicotinamide metabolism may be a key mechanism by which composite probiotics enhance CAC-FOLFOX prognosis. Probiotics counteract FOLFOX-induced NAD⁺ depletion via downregulating NNMT to reduce nicotinamide loss and reshaping microbiota to enhance nicotinic acid production.
Institute
Lanzhou University
DepartmentSchool of Life Sciences
LaboratoryProbiotics and Life Health Institute
Last NameChen
First NameHu
AddressLanzhou University, Lanzhou City, Gansu Province, China
Emailchenhu21@lzu.edu.cn
Phone13732910293
Submit Date2025-11-14
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2025-12-19
Release Version1
Hu Chen Hu Chen
https://dx.doi.org/10.21228/M8P25P
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002785
Project DOI:doi: 10.21228/M8P25P
Project Title:Effects of a Complex Probiotic Intervention on Serum Metabolism and Tumor-Bearing Intestinal Segment Metabolism in FOLFOX Chemotherapy-Treated Mice with Colorectal Cancer
Project Summary:An AOM/DSS-induced inflammation-associated colorectal cancer mouse model was established to investigate the metabolic changes in FOLFOX chemotherapy with and without complex probiotic intervention.
Institute:Lanzhou University
Department:School of Life Sciences
Laboratory:Probiotics and Life Health Institute
Last Name:Chen
First Name:Hu
Address:Lanzhou University, Lanzhou City, Gansu Province, China, lanzhou, Gansu, 730000, China
Email:chenhu21@lzu.edu.cn
Phone:13732910293

Subject:

Subject ID:SU004565
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Female
Animal Animal Supplier:Laboratory Animal Center, Lanzhou University
Animal Housing:Five mice were housed in individually ventilated cages.
Animal Light Cycle:12 h light/dark cycle
Animal Feed:standard diet ad libitum
Animal Water:Provide a 2% DSS solution or normal drinking water on a regular basis.
Animal Inclusion Criteria:eight-week-old BALB/c

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Treatment
SA521341B1Tcolonic tissue AOM/DSS
SA521342B6Tcolonic tissue AOM/DSS
SA521343B5Tcolonic tissue AOM/DSS
SA521344B4Tcolonic tissue AOM/DSS
SA521345B3Tcolonic tissue AOM/DSS
SA521346B2Tcolonic tissue AOM/DSS
SA521347F2Tcolonic tissue AOM/DSS+FOLFOX
SA521348F1Tcolonic tissue AOM/DSS+FOLFOX
SA521349F3Tcolonic tissue AOM/DSS+FOLFOX
SA521350F4Tcolonic tissue AOM/DSS+FOLFOX
SA521351F5Tcolonic tissue AOM/DSS+FOLFOX
SA521352F6Tcolonic tissue AOM/DSS+FOLFOX
SA521353G1Tcolonic tissue AOM/DSS+FOLFOX+Probiotics
SA521354G5Tcolonic tissue AOM/DSS+FOLFOX+Probiotics
SA521355G4Tcolonic tissue AOM/DSS+FOLFOX+Probiotics
SA521356G3Tcolonic tissue AOM/DSS+FOLFOX+Probiotics
SA521357G6Tcolonic tissue AOM/DSS+FOLFOX+Probiotics
SA521358G2Tcolonic tissue AOM/DSS+FOLFOX+Probiotics
SA521359H1Tcolonic tissue AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521360H6Tcolonic tissue AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521361H4Tcolonic tissue AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521362H3Tcolonic tissue AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521363H2Tcolonic tissue AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521364H5Tcolonic tissue AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521365A2Tcolonic tissue Control
SA521366A1Tcolonic tissue Control
SA521367A3Tcolonic tissue Control
SA521368A4Tcolonic tissue Control
SA521369A5Tcolonic tissue Control
SA521370A6Tcolonic tissue Control
SA521371B6Sserum AOM/DSS
SA521372B1Sserum AOM/DSS
SA521373B4Sserum AOM/DSS
SA521374B3Sserum AOM/DSS
SA521375B5Sserum AOM/DSS
SA521376B2Sserum AOM/DSS
SA521377F1Sserum AOM/DSS+FOLFOX
SA521378F2Sserum AOM/DSS+FOLFOX
SA521379F3Sserum AOM/DSS+FOLFOX
SA521380F4Sserum AOM/DSS+FOLFOX
SA521381F5Sserum AOM/DSS+FOLFOX
SA521382F6Sserum AOM/DSS+FOLFOX
SA521383G3Sserum AOM/DSS+FOLFOX+Probiotics
SA521384G6Sserum AOM/DSS+FOLFOX+Probiotics
SA521385G5Sserum AOM/DSS+FOLFOX+Probiotics
SA521386G4Sserum AOM/DSS+FOLFOX+Probiotics
SA521387G2Sserum AOM/DSS+FOLFOX+Probiotics
SA521388G1Sserum AOM/DSS+FOLFOX+Probiotics
SA521389H2Sserum AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521390H4Sserum AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521391H3Sserum AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521392H5Sserum AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521393H6Sserum AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521394H1Sserum AOM/DSS+FOLFOX+Probiotics+Loperamide
SA521395A6Sserum Control
SA521396A5Sserum Control
SA521397A2Sserum Control
SA521398A3Sserum Control
SA521399A4Sserum Control
SA521400A1Sserum Control
Showing results 1 to 60 of 60

Collection:

Collection ID:CO004558
Collection Summary:Blood and colon tissue were collected from mice immediately after euthanasia. Serum was obtained by centrifuging the blood after it had sufficiently settled. Colon tissue was identified by personnel with specialized anatomical expertise, who excised tumor-bearing intestinal segments. These segments were rinsed with pre-chilled PBS buffer and rapidly frozen in liquid nitrogen for subsequent analysis.
Sample Type:serum and colonic tissue
Volumeoramount Collected:100 μL and 200 mg
Storage Conditions:-80℃
Collection Tube Temp:4℃

Treatment:

Treatment ID:TR004574
Treatment Summary:For the azoxymethane plus dextran sulfate sodium (AOM/DSS) model, 8-week-old female BALB/c mice were intraperitoneally injected with 10 mg/kg AOM (Sigma-Aldrich, Saint Louis, USA), followed by three cycles of DSS (MP Biomedicals, Ohio, USA) to mimic colitis-associated colorectal cancer (CAC). For each cycle, the mice were given free access to drinking water supplemented with 2% DSS for 1 week, followed by 2 weeks of regular water. FOLFOX treatment was consistently applied in FOLFOX-induced injury, AOM/DSS-induced CAC, and MC38 tumor models. Following a one-week intervention with composite probiotics or vehicle, oxaliplatin (1 mg/kg) was administered intraperitoneally, followed by daily intraperitoneal injections of 5-fluorouracil (50 mg/kg) and calcium folinate (10 mg/kg) for 5 days. All solutions were freshly prepared in sterile saline before administration. The control group received an equivalent volume of saline via intraperitoneal injection. On the day of oxaliplatin injection, loperamide (0.2 mg/day) was administered via oral gavage to the designated mice, according to the experimental protocol.
Treatment Compound:AOM, DSS, Loperamide, 5-fluorouracil, oxaliplatin, calcium folinate
Treatment Route:Intraperitoneal injection/ gavage
Treatment Doseduration:About three months
Treatment Vehicle:normal saline
Animal Anesthesia:Pentobarbital Sodium
Animal Acclimation Duration:2 weeks
Animal Fasting:12 hours before sacrifice
Animal Endp Euthanasia:excessive anesthesia euthanasia

Sample Preparation:

Sampleprep ID:SP004571
Sampleprep Summary:Metabolites Extraction of serum: 100 μL of serum was taken, mixed with 400 μL of extraction solution (MeOH:ACN, 1:1 (v/v)), the extraction solution contain deuterated internal standards, the mixed solution were vortexed for 30 s, sonicated for 10 min in 4 ℃ water bath, and incubated for 1 h at -40 ℃ to precipitate proteins. Then the samples were centrifuged at 12000 rpm (RCF=13800(×g),R= 8.6cm) for 15 min at 4 ℃. The supernatant was transferred to a fresh glass vial for analysis. The quality control (QC) sample was prepared by mixing an equal aliquot of the supernatant of samples. Metabolites Extraction of Solid: The animal tissue samples (25 mg±1 mg) were taken, mixed with beads and 500 μL of extraction solution (MeOH:ACN:H2O, 2:2:1 (v/v)). The extraction solution contain deuterated internal standards. The mixed solution were vortexed for 30 s. Then the mixed samples were homogenized (35 Hz,4 min) and sonicated for 5 min in 4 ℃ water bath, the step repeat for three times. The samples were incubated for 1 h at -40 ℃ to precipitate proteins. Then the samples ware centrifuged at 12000 rpm (RCF=13800(×g),R= 8.6cm) for 15 min at 4 ℃. The supernatant was transferred to a fresh glass vial for analysis. The quality control (QC) sample was prepared by mixing an equal aliquot of the supernatant of samples.
Processing Storage Conditions:-80℃
Extract Storage:-80℃

Combined analysis:

Analysis ID AN007367 AN007368
Chromatography ID CH005582 CH005582
MS ID MS007061 MS007062
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Vanquish Thermo Vanquish
Column Waters ACQUITY UPLC BEH Amide (50 x 2.1mm,1.7um) Waters ACQUITY UPLC BEH Amide (50 x 2.1mm,1.7um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Orbitrap Exploris 120 Thermo Orbitrap Exploris 120
Ion Mode POSITIVE NEGATIVE
Units peak area peak area

Chromatography:

Chromatography ID:CH005582
Chromatography Summary:For polar metabolites, LC-MS/MS analyses were performed using an UHPLC system (Vanquish, Thermo Fisher Scientific) with a Waters ACQUITY UPLC BEH Amide (2.1 mm × 50 mm, 1.7 μm) coupled to Orbitrap Exploris 120 mass spectrometer (Orbitrap MS, Thermo). The mobile phase consisted of 25 mmol/L ammonium acetate and 25 ammonia hydroxide in water(pH = 9.75)(A) and acetonitrile (B). The auto-sampler temperature was 4 ℃, and the injection volume was 2 μL.
Instrument Name:Thermo Vanquish
Column Name:Waters ACQUITY UPLC BEH Amide (50 x 2.1mm,1.7um)
Column Temperature:25
Flow Gradient:0-0.25min, 95% B; 0.25-3.5min, 95%-65%B; 3.5-4min, 65%B-40%B; 4-4.5min, 40%B; 4.5-4.55min, 40%-95%B; 4.55-6min, 95%B
Flow Rate:0.5 mL/min
Injection Temperature:4
Solvent A:100% water; 25mM ammonium acetate; 25mM ammonium hydroxide; pH = 9.75
Solvent B:100% Acetonitrile
Chromatography Type:HILIC

MS:

MS ID:MS007061
Analysis ID:AN007367
Instrument Name:Thermo Orbitrap Exploris 120
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The Orbitrap Exploris 120 mass spectrometer was used for its ability to acquire MS/MS spectra on information-dependent acquisition (IDA) mode in the control of the acquisition software (Xcalibur, Thermo). In this mode, the acquisition software continuously evaluates the full scan MS spectrum. The ESI source conditions were set as following: sheath gas flow rate as 50 Arb, Aux gas flow rate as 15 Arb, capillary temperature 320 ℃, full MS resolution as 60000, MS/MS resolution as 15000, collision energy: SNCE 20/30/40, spray voltage as 3.8 kV (positive)
Ion Mode:POSITIVE
  
MS ID:MS007062
Analysis ID:AN007368
Instrument Name:Thermo Orbitrap Exploris 120
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The Orbitrap Exploris 120 mass spectrometer was used for its ability to acquire MS/MS spectra on information-dependent acquisition (IDA) mode in the control of the acquisition software (Xcalibur, Thermo). In this mode, the acquisition software continuously evaluates the full scan MS spectrum. The ESI source conditions were set as following: sheath gas flow rate as 50 Arb, Aux gas flow rate as 15 Arb, capillary temperature 320 ℃, full MS resolution as 60000, MS/MS resolution as 15000, collision energy: SNCE 20/30/40, spray voltage was -3.4 kV (negative).
Ion Mode:NEGATIVE
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