Gut Dysbiosis and Abnormal Bile Acid Metabolism in Colitis-Associated Cancer
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Liu L, Yang M, Dong W, Liu T, Song X, Gu Y, Wang S, Liu Y, Abla Z, Qiao X, Liu W, Jiang K, Wang B, Zhang J, Cao H
Journal
Gastroenterology research and practice
Year
2021
BACKGROUND: Patients with prolonged inflammatory bowel disease (IBD) can develop into colorectal cancer (CRC), also called colitis-associated cancer (CAC). Studies have shown the association between gut dysbiosis, abnormal bile acid metabolism, and inflammation process. Here, we aimed to investigate these two factors in the CAC model. METHODS: C57BL/6 mice were randomly allocated to two groups: azoxymethane/dextran sodium sulfate (AOM/DSS) and control. The AOM/DSS group received AOM injection followed by DSS drinking water. Intestinal inflammation, mucosal barrier, and bile acid receptors were determined by real-time PCR and immunohistochemistry. Fecal microbiome and bile acids were detected via 16S rRNA sequencing and liquid chromatography-mass spectrometry. RESULTS: The AOM/DSS group exhibited severe mucosal barrier impairment, inflammatory response, and tumor formation. In the CAC model, the richness and biodiversity of gut microbiota were decreased, along with significant alteration of composition. The abundance of pathogens was increased, while the short-chain fatty acids producing bacteria were reduced. Interestingly, Clostridium XlV and Lactobacillus, which might be involved in the bile acid deconjugation, transformation, and desulfation, were significantly decreased. Accordingly, fecal bile acids were decreased, accompanied by reduced transformation of primary to secondary bile acids. Given bile acid receptors, the ileum farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis was downregulated, while Takeda G-protein receptor 5 (TGR5) was overexpressed in colonic tumor tissues. CONCLUSION: Gut dysbiosis might alter the metabolism of bile acids and promote CAC, which would provide a potential preventive strategy of CAC by regulating gut microbiota and bile acid metabolism.
Experiment 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-18
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Colorectal cancer cell line CRC cell line,Colorectal cancer cell line,colorectal cancer cell line
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- control group at week 10 (C10 group)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- azoxymethane/dextran sodiumsulfate (AOM/DSS) group at week 10 (AD10 group)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- C57BL/6mice aged 7 weeks were obtained from Beijing Huafukang Bioscience Co. Inc. and acclimatized 1 week before the experiment. Intraperitoneal injection of 10mg/kg azoxymethane(AOM) was applied to the AOM/DSS group. After seven days, the AOM/DSS group was given1.5% dextran sodium sulfate (DSS) in drinking water on days 8–13, 27–32, and 46–51, and each cycle of DSS treatment was followed by 14-day drinking water. This was to create the colitis-induced colorectal cancer (CAC) model in the mice. Group 1 is the mice that developed CAC and had their fecal sample collected before being euthanized on day 70 (week 10).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 5
- Group 1 sample size Number of subjects in the case (exposed) group
- 5
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- none
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-18
Source: Figure 4c
Description: The LefSe analysis listed bacteria with significant differences at different levels in AD10 group vs C10 group
Abundance in Group 1: decreased abundance in azoxymethane/dextran sodiumsulfate (AOM/DSS) group at week 10 (AD10 group)
| NCBI | Quality Control | Links |
|---|---|---|
| Alistipes | ||
| Bacteroidales | ||
| Bacteroidia | ||
| Clostridiaceae | ||
| Clostridium | ||
| Desulfovibrio | ||
| Lachnospiraceae incertae sedis | ||
| Odoribacter | ||
| Porphyromonadaceae | ||
| Rikenellaceae |
Revision editor(s): Yjung24, ChiomaBlessing
Signature 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-18
Source: Figure 4c
Description: The LefSe analysis listed bacteria with significant differences at different levels in AD10 group vs C10 group
Abundance in Group 1: increased abundance in azoxymethane/dextran sodiumsulfate (AOM/DSS) group at week 10 (AD10 group)
Revision editor(s): Yjung24, ChiomaBlessing
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