Summary of Study ST003028
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 PR001881. The data can be accessed directly via it's Project DOI: 10.21228/M8KF0N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003028 |
| Study Title | Chronic stress dampens Lactobacillus johnsonii-mediated tumor suppression to enhance colorectal cancer progression |
| Study Summary | Colorectal cancer (CRC) development and outcome are impacted by modifiable risk factors, including psychological stress. The gut microbiota has also been shown to be linked to psychological factors. Here, we found a marked deteriorative effect of chronic stress in multiple CRC models, including chemically-induced (AOM/DSS), genetically engineered (APCmin/+), and xenograft tumor mouse models. RNA-seq data from colon tissues revealed that expression of stemness-related genes was upregulated in the stressed CRC group by activated β-catenin signaling, which was further confirmed by results from ex vivo organoid analyses as well as in vitro and in vivo cell tumorigenicity assays. 16S rRNA sequencing of the gut microbiota showed that chronic stress disrupted gut microbes, and antibiotic treatment and fecal microbiota transplantation abolished the stimulatory effects of chronic stress on CRC progression. Stressed CRC mice displayed a significant decrease in Lactobacillus johnsonii (L. johnsonii) abundance, which was inversely correlated with tumor load. Moreover, protocatechuic acid (PCA) was identified as a beneficial metabolite produced by L. johnsonii based on metabolome sequencing and LC‒MS/MS analysis. Replenishment of L. johnsonii or PCA blocked chronic stress-induced CRC progression by decreasing β-catenin expression. Furthermore, PCA activated the cGMP pathway, and the cGMP agonist sildenafil abolished the effects of chronic stress on CRC. Altogether, these data identify that stress impacts the gut microbiome to support CRC progression. |
| Institute | China Pharmaceutical University |
| Last Name | Cao |
| First Name | Qiuhua |
| Address | No. 639 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211198, China |
| 1520210058@cpu.edu.cn | |
| Phone | +86-25-86185622 |
| Submit Date | 2023-12-21 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-01-03 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001881 |
| Project DOI: | doi: 10.21228/M8KF0N |
| Project Title: | Chronic stress dampens Lactobacillus johnsonii-mediated tumor suppression to enhance colorectal cancer progression |
| Project Summary: | Colorectal cancer (CRC) development and outcome are impacted by modifiable risk factors, including psychological stress. The gut microbiota has also been shown to be linked to psychological factors. Here, we found a marked deteriorative effect of chronic stress in multiple CRC models, including chemically-induced (AOM/DSS), genetically engineered (APCmin/+), and xenograft tumor mouse models. RNA-seq data from colon tissues revealed that expression of stemness-related genes was upregulated in the stressed CRC group by activated β-catenin signaling, which was further confirmed by results from ex vivo organoid analyses as well as in vitro and in vivo cell tumorigenicity assays. 16S rRNA sequencing of the gut microbiota showed that chronic stress disrupted gut microbes, and antibiotic treatment and fecal microbiota transplantation abolished the stimulatory effects of chronic stress on CRC progression. Stressed CRC mice displayed a significant decrease in Lactobacillus johnsonii (L. johnsonii) abundance, which was inversely correlated with tumor load. Moreover, protocatechuic acid (PCA) was identified as a beneficial metabolite produced by L. johnsonii based on metabolome sequencing and LC‒MS/MS analysis. Replenishment of L. johnsonii or PCA blocked chronic stress-induced CRC progression by decreasing β-catenin expression. Furthermore, PCA activated the cGMP pathway, and the cGMP agonist sildenafil abolished the effects of chronic stress on CRC. Altogether, these data identify that stress impacts the gut microbiome to support CRC progression. |
| Institute: | China Pharmaceutical University |
| Last Name: | Cao |
| First Name: | Qiuhua |
| Address: | No. 639 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211198, China |
| Email: | 1520210058@cpu.edu.cn |
| Phone: | +86-25-86185622 |
Subject:
| Subject ID: | SU003142 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA328071 | A28 | AOM/DSS |
| SA328072 | A49 | AOM/DSS |
| SA328073 | A42 | AOM/DSS |
| SA328074 | A30 | AOM/DSS |
| SA328075 | A40 | AOM/DSS |
| SA328076 | AS153 | AOM/DSS and chronic restraint stress |
| SA328077 | AS78 | AOM/DSS and chronic restraint stress |
| SA328078 | AS53 | AOM/DSS and chronic restraint stress |
| SA328079 | AS58 | AOM/DSS and chronic restraint stress |
| SA328080 | AS63 | AOM/DSS and chronic restraint stress |
| Showing results 1 to 10 of 10 |
Collection:
| Collection ID: | CO003135 |
| Collection Summary: | The colons were dissected and washed, and then flash-frozen in liquid N2 |
| Sample Type: | Colon |
Treatment:
| Treatment ID: | TR003151 |
| Treatment Summary: | The mice were intraperitoneally injected with 10 mg/kg azoxymethane (AOM) on the first day and then given 2% dextran sulfate sodium (DSS) for one week and water for two weeks (three cycles). And the stressed mice were confined in a ventilated 50 mL tube and stressed for 3-4 h daily. All mice were dissected 8 weeks after the start of the experiment. |
Sample Preparation:
| Sampleprep ID: | SP003148 |
| Sampleprep Summary: | Sample was thawed on ice. Take 50 mg of one sample and homogenize it with 1000 μl of ice-cold methanol/water (70%, v/v). Add cold steel balls to the mixture and homogenate for at 30 Hz for 3 min. Whirl the mixture for 1 min, and then centrifuge it with 12,000 rpm at 4°C for 10 min. The collected supernatant will be used for LC-MS/MS analysis. |
Combined analysis:
| Analysis ID | AN004964 | AN004965 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | SCIEX ExionLC AD | SCIEX ExionLC AD |
| Column | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) |
| MS Type | ESI | ESI |
| MS instrument type | QTRAP | QTRAP |
| MS instrument name | ABI Sciex 6500 QTrap | ABI Sciex 6500 QTrap |
| Ion Mode | NEGATIVE | POSITIVE |
| Units | count per second (cps) | count per second (cps) |
Chromatography:
| Chromatography ID: | CH003747 |
| Instrument Name: | SCIEX ExionLC AD |
| Column Name: | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) |
| Column Temperature: | 40°C |
| Flow Gradient: | 0.4 mL/min |
| Flow Rate: | 95:5 V/V at 0 min, 5:95 V/V at 11.0 min, 5:95 V/V at 12.0 min, 95:5 V/V at 12.1 min, 95:5 V/V at 14.0 min |
| Solvent A: | water (0.04% acetic acid) |
| Solvent B: | acetonitrile (0.04% acetic acid) |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS004704 |
| Analysis ID: | AN004964 |
| Instrument Name: | ABI Sciex 6500 QTrap |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | In this study, we performed extensive targeted detection of metabolites in the colon using MRM scanning modalities. Therefore, we did not perform MS/MS data annotation. In the MRM mode, the quadrupole firstly screens the precursor ion (parent ion) of the target substance and excludes the ions corresponding to other molecular weight substances in order to preliminarily exclude the interference; the precursor ion is induced to ionize by the collision chamber and breaks off to form a lot of fragment ions, and the fragment ions are then filtered through the triple quadrupole to select a desired characteristic fragment ion and exclude the interference of non-target ions. We used MultiQuant software to analyze the data. |
| Ion Mode: | NEGATIVE |
| MS ID: | MS004705 |
| Analysis ID: | AN004965 |
| Instrument Name: | ABI Sciex 6500 QTrap |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | In this study, we performed extensive targeted detection of metabolites in the colon using MRM scanning modalities. Therefore, we did not perform MS/MS data annotation. In the MRM mode, the quadrupole firstly screens the precursor ion (parent ion) of the target substance and excludes the ions corresponding to other molecular weight substances in order to preliminarily exclude the interference; the precursor ion is induced to ionize by the collision chamber and breaks off to form a lot of fragment ions, and the fragment ions are then filtered through the triple quadrupole to select a desired characteristic fragment ion and exclude the interference of non-target ions. We used MultiQuant software to analyze the data. |
| Ion Mode: | POSITIVE |
