The efficacy of prevention for colon cancer based on the microbiota therapy and the antitumor mechanisms with intervention of dietary Lactobacillus
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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
Xu F, Li Q, Wang S, Dong M, Xiao G, Bai J, Wang J, Sun X
Journal
Microbiology spectrum
Year
2023
Keywords:
Lactobacillus, colon cancer, gut microbiota, serine, sphingosine 1-phosphate signaling
Gut microbiota and their secreted metabolites have an influence on the initiation and progression of colon cancer. Probiotics are extensively perceived as a potential microbiota-modulation strategy to promote the health of the host, while the effectiveness of preventing colon cancer based on microbiota therapy has not been confirmed, and antitumor mechanisms influenced by microbiota and their metabolites with the intervention of probiotics remain to be further investigated. In vitro, Lactobacillus (JY300-8 and JMR-01) significantly inhibited the proliferation of CT26, HT29, and HCT116 cells. Moreover, we studied the prevention and therapy efficiency of Lactobacillus and its underlying antitumor mechanism through the alteration of gut microbiota and their metabolites regulated by Lactobacillus in colon cancer models in mice. We demonstrated that the pre-administration of Lactobacillus (JY300-8 and JMR-01) for 20 days before establishing tumor models resulted in an 86.21% reduction in tumor formation rate compared to tumor control group. Subsequently, continuous oral administration of living Lactobacillus significantly suppresses tumor growth, and tumor volumes decrease by 65.2%. Microbiome and metabolome analyses reveal that Lactobacillus suppresses colonic tumorigenesis and progression through the modulation of gut microbiota homeostasis and metabolites, including the down-regulation of secondary bile acids, sphingosine 1-phosphate (S1P), and pyrimidine metabolism, as well as the production of anticarcinogenic compounds in tumor-bearing mice. Additionally, metabolome analyses of Lactobacillus (JY300-8 and JMR-01) indicate that living Lactobacillus could reduce the relative abundance of alanine and L-serine to suppress tumor progression by regulating the tumor microenvironment, including down-regulation of pyrimidine metabolism and S1P signaling in cancer. These findings provide a potential prevention strategy and therapeutic target for colon cancer through the intervention of dietary Lactobacillus. IMPORTANCE The modulation of gut microbiota and metabolites has a significant influence on the progression of colon cancer. Our research indicated that the intervention of probiotics is a potentially feasible strategy for preventing colon cancer. We have also revealed the underlying antitumor mechanism through the alteration of gut microbiota and their metabolites, which could lead to broader biomedical impacts on the prevention and therapy of colon cancer with microbiota-based therapy regulated by probiotics.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2024-4-6
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 cancer of colorectum,cancer of large bowel,cancer of large intestine,cancer of the large bowel,colon cancer,colorectal cancer,colorectum cancer,CRC,large intestine cancer,malignant colorectal neoplasm,malignant colorectal tumor,malignant colorectum neoplasm,malignant large bowel neoplasm,malignant large bowel tumor,malignant large intestine neoplasm,malignant large intestine tumor,malignant neoplasm of colorectum,malignant neoplasm of large bowel,malignant neoplasm of large intestine,malignant neoplasm of the large bowel,malignant neoplasm of the large intestine,malignant tumor of large bowel,malignant tumor of large intestine,malignant tumor of the large bowel,malignant tumor of the large intestine,Colorectal cancer
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Tumor control group (CK)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Living bacteria group (LB)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- BALB/c mice (male, 6 wk) purchased from Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences. These mice were given oral administration of living Lactobacillus bacteria.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 30
- Group 1 sample size Number of subjects in the case (exposed) group
- 30
- 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
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2.0
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-4-6
Source: Figure 3g
Description: Effects of administration of Lactobacillus on living bacteria group(LB). The gut microbiota with the capacity of producing antitumor compounds are increased in living bacteria group.
Abundance in Group 1: increased abundance in Living bacteria group (LB)
Revision editor(s): Manisha28, Svetlana up
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-4-6
Source: Figure 3g
Description: Effects of administration of Lactobacillus on living bacteria group(LB). Some gut microbiota are decreased in living bacteria group.
Abundance in Group 1: decreased abundance in Living bacteria group (LB)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidales | ||
| Butyricimonas | ||
| Cyanobacteriota | ||
| Rikenellaceae | ||
| Sphingomonadaceae | ||
| Sphingomonas | ||
| Streptophyta |
Revision editor(s): Manisha28, Svetlana up
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-4-6
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Inactivated bacteria group (IB)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- BALB/c mice (male, 6 wk) purchased from Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences. These mice were given oral administration of inactivated Lactobacillus bacteria.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-4-6
Source: Figure 3g
Description: Effects of administration of inactive Lactobacillus on inactivated bacteria group(IB). The abundance of microbial flora in inactivated bacteria group was significantly higher than that of the tumor control group (P < 0.001).
Abundance in Group 1: increased abundance in Inactivated bacteria group (IB)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Caulobacteraceae | ||
| Clostridia | ||
| Coprococcus | ||
| Eubacteriales |
Revision editor(s): Manisha28, Svetlana up
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-4-6
Source: Figure 3g
Description: Effects of administration of inactive Lactobacillus on inactivated bacteria group(IB). The abundance of microbial flora in inactivated bacteria group was significantly higher than that of the tumor control group (P < 0.001). However, some bacteria groups decreased.
Abundance in Group 1: decreased abundance in Inactivated bacteria group (IB)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidales | ||
| Bacteroides | ||
| Bacteroidia | ||
| Prevotella | ||
| Prevotellaceae |
Revision editor(s): Manisha28, Svetlana up
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2024-4-6
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Inactivated bacteria group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Living bacteria group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- BALB/c mice (male, 6 wk) purchased from Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences. These mice were given oral administration of living Lactobacillus bacteria.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-4-6
Source: Figure 3g
Description: LEfSe results of Inactivated vs Living Bacteria group
Abundance in Group 1: decreased abundance in Living bacteria group
| NCBI | Quality Control | Links |
|---|---|---|
| Alphaproteobacteria | ||
| Cyanobacteriota | ||
| Oscillospiraceae bacterium | ||
| Rickettsiales | ||
| Rikenellaceae |
Revision editor(s): Svetlana up
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-4-6
Source: Figure 3g
Description: LEfSe results of Inactivated vs Living Bacteria group
Abundance in Group 1: increased abundance in Living bacteria group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacilli | ||
| Enterobacterales | ||
| Enterobacteriaceae | ||
| Escherichia | ||
| Gammaproteobacteria | ||
| Lactobacillaceae | ||
| Lactobacillales | ||
| Lactobacillus |
Revision editor(s): Svetlana up
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