Depicting the landscape of gut microbial-metabolic interaction and microbial-host immune heterogeneity in deficient and proficient DNA mismatch repair colorectal cancers
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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
Li J, Guo Y, Liu J, Guo F, Du L, Yang Y, Li X, Ma Y
Journal
Journal for immunotherapy of cancer
Year
2023
Keywords:
gastrointestinal neoplasms
BACKGROUND: Accumulating evidence has indicated the role of gut microbiota in remodeling host immune signatures, but various interplays underlying colorectal cancers (CRC) with deficient DNA mismatch repair (dMMR) and proficient DNA mismatch repair (pMMR) remain poorly understood. This study aims to decipher the gut microbiome-host immune interactions between dMMR and pMMR CRC. METHOD: We performed metagenomic sequencing and metabolomic analysis of fecal samples from a cohort encompassing 455 participants, including 21 dMMR CRC, 207 pMMR CRC, and 227 healthy controls. Among them, 50 tumor samples collected from 5 dMMR CRC and 45 pMMR CRC were conducted bulk RNA sequencing. RESULTS: Pronounced microbiota and metabolic heterogeneity were identified with 211 dMMR-enriched species, such as Fusobacterium nucleatum and Akkermansia muciniphila, 2 dMMR-depleted species, such as Flavonifractor plautii, 13 dMMR-enriched metabolites, such as retinoic acid, and 77 dMMR-depleted metabolites, such as lactic acid, succinic acid, and 2,3-dihydroxyvaleric acid. F. plautii was enriched in pMMR CRC and it was positively associated with fatty acid degradation, which might account for the accumulation of dMMR-depleted metabolites classified as short chain organic acid (lactic acid, succinic acid, and 2,3-dihydroxyvaleric acid) in pMMR CRC. The microbial-metabolic association analysis revealed the characterization of pMMR CRC as the accumulation of lactate induced by the depletion of specific gut microbiota which was negatively associated with antitumor immune, whereas the nucleotide metabolism and peptide degradation mediated by dMMR-enriched species characterized dMMR CRC. MMR-specific metabolic landscapes were related to distinctive immune features, such as CD8+ T cells, dendritic cells and M2-like macrophages. CONCLUSIONS: Our mutiomics results delineate a heterogeneous landscape of microbiome-host immune interactions within dMMR and pMMR CRC from aspects of bacterial communities, metabolic features, and correlation with immunocyte compartment, which infers the underlying mechanism of heterogeneous immune responses.
Experiment 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-19
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- 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
- Mismatch repair cancer syndrome Mismatch repair cancer syndrome,mismatch repair cancer syndrome
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- proficient DNA mismatch repair (pMMR) CRC
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- deficient DNA mismatch repair (dMMR) CRC
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- dMMR in colorectal cancer (CRC) characterized by robust immune environment
- Group 0 sample size Number of subjects in the control (unexposed) group
- 207
- Group 1 sample size Number of subjects in the case (exposed) group
- 21
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- 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
- Linear Regression
- 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
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-19
Source: Table S2, Figure 2c
Description: Differential microbial abundance between deficient DNA mismatch repair (dMMR) and proficient DNA mismatch repair (pMMR) in CRC
Abundance in Group 1: increased abundance in deficient DNA mismatch repair (dMMR) CRC
Revision editor(s): ChiomaBlessing
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-19
Source: Table S2
Description: Differential microbial abundance between deficient DNA mismatch repair (dMMR) and proficient DNA mismatch repair (pMMR) in CRC
Abundance in Group 1: decreased abundance in deficient DNA mismatch repair (dMMR) CRC
| NCBI | Quality Control | Links |
|---|---|---|
| Flavonifractor plautii | ||
| Gemella haemolysans |
Revision editor(s): ChiomaBlessing
Experiment 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-19
Differences from previous experiment shown
Subjects
- 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
- Healthy controls (CTRL)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 227
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-19
Source: Figure 2c
Description: Differential microbial abundance between deficient DNA mismatch repair (dMMR) in CRC and healthy controls (CTRL)
Abundance in Group 1: increased abundance in deficient DNA mismatch repair (dMMR) CRC
Revision editor(s): ChiomaBlessing
Experiment 3
Reviewed Marked as Reviewed by Folakunmi on 2024-1-19
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- proficient DNA mismatch repair (pMMR) CRC
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- pMMR in colorectal cancer (CRC) characterized by immunosuppressive tumor microenvironment
- Group 1 sample size Number of subjects in the case (exposed) group
- 207
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-19
Source: Figure 2c
Description: Differential microbial abundance between proficient DNA mismatch repair (pMMR) in CRC and healthy controls (CTRL)
Abundance in Group 1: increased abundance in proficient DNA mismatch repair (pMMR) CRC
| NCBI | Quality Control | Links |
|---|---|---|
| Flavonifractor plautii |
Revision editor(s): ChiomaBlessing
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-19
Source: Figure 2c
Description: Differential microbial abundance between proficient DNA mismatch repair (pMMR) in CRC and healthy controls (CTRL)
Abundance in Group 1: decreased abundance in proficient DNA mismatch repair (pMMR) CRC
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerotignum propionicum | ||
| Collinsella aerofaciens | ||
| Gordonibacter pamelaeae |
Revision editor(s): ChiomaBlessing
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