Long-term follow-up of colorectal cancer screening attendees identifies differences in Phascolarctobacterium spp. using 16S rRNA and metagenome sequencing
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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
Bucher-Johannessen C, Birkeland EE, Vinberg E, Bemanian V, Hoff G, Berstad P, Rounge TB
Journal
Frontiers in oncology
Year
2023
Keywords:
16S rRNA, archived fecal samples, colorectal cancer screening, long term follow-up, metagenome, microbiome, sequencing
BACKGROUND: The microbiome has been implicated in the initiation and progression of colorectal cancer (CRC) in cross-sectional studies. However, there is a lack of studies using prospectively collected samples. METHODS: From the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, we analyzed 144 archived fecal samples from participants who were diagnosed with CRC or high-risk adenoma (HRA) at screening and from participants who remained cancer-free during 17 years of follow-up. We performed 16S rRNA sequencing of all the samples and metagenome sequencing on a subset of 47 samples. Differences in taxonomy and gene content between outcome groups were assessed for alpha and beta diversity and differential abundance. RESULTS: Diversity and composition analyses showed no significant differences between CRC, HRA, and healthy controls. Phascolarctobacterium succinatutens was more abundant in CRC compared with healthy controls in both the 16S and metagenome data. The abundance of Bifidobacterium and Lachnospiraceae spp. was associated with time to CRC diagnosis. CONCLUSION: Using a longitudinal study design, we identified three taxa as being potentially associated with CRC. These should be the focus of further studies of microbial changes occurring prior to CRC diagnosis.
Experiment 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Subjects
- Location of subjects
- Norway
- 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
- Colorectal adenoma adenoma of large bowel,adenoma of large intestine,adenoma of the large bowel,adenoma of the large intestine,colorectal adenoma,colorectum adenoma,large bowel adenoma,large intestine adenoma,Colorectal adenoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HRA (high-risk adenoma)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Individuals selected from available archive of fresh-frozen stool samples with high-risk adenomas were defined as those presenting with one or more adenomas of ≥10 mm, with high-grade dysplasia or villous components regardless of polyp size, or those with three or more adenomas regardless of size, dysplasia, and villosity.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 53
- Group 1 sample size Number of subjects in the case (exposed) group
- 63
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).
- raw counts
- Statistical test
- Negative Binomial 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)?
- Yes
- Matched on Factors on which subjects have been matched on in a case-control study
- age, time, sex
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- sex, geographic area
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Source: Table 2
Description: Differential abundance analyses of taxa and pathways between CRC, HRA, and healthy controls.
Abundance in Group 1: decreased abundance in HRA (high-risk adenoma)
| NCBI | Quality Control | Links |
|---|---|---|
| Azospirillum sp. 47_25 | ||
| Escherichia/Shigella sp. | ||
| Pseudomonadota |
Experiment 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
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 1 name Corresponds to the case (exposed) group for case-control studies
- CRC (participants diagnosed with colorectal cancer)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- participants who were diagnosed with colorectal cancer at screening during the Norwegian Colorectal Prevention trial or by registry follow-up selected from available archive of fresh-frozen stool samples.
- Group 1 sample size Number of subjects in the case (exposed) group
- 28
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Source: Table 2
Description: Differential abundance analyses of taxa and pathways between CRC, HRA, and healthy controls.
Abundance in Group 1: increased abundance in CRC (participants diagnosed with colorectal cancer)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| unclassified Phascolarctobacterium |
Experiment 3
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Colorectal adenoma , Colorectal cancer adenoma of large bowel,adenoma of large intestine,adenoma of the large bowel,adenoma of the large intestine,colorectal adenoma,colorectum adenoma,large bowel adenoma,large intestine adenoma,Colorectal adenoma,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 1 name Corresponds to the case (exposed) group for case-control studies
- HRA (high-risk adenoma) group combined with CRC (colorectal cancer) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Individuals selected from available archive of fresh-frozen stool samples with high-risk adenomas were defined as those presenting with one or more adenomas of ≥10 mm, with high-grade dysplasia or villous components regardless of polyp size, or those with three or more adenomas regardless of size, dysplasia, and villosity. Combined with individuals selected from available archive of fresh-frozen stool samples diagnosed with colorectal cancer at screening or by registry follow-up.
- Group 1 sample size Number of subjects in the case (exposed) group
- 91
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- geographic area, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Source: Table 2
Description: Differential abundance analyses of taxa and pathways between CRC, HRA, and healthy controls.
Abundance in Group 1: increased abundance in HRA (high-risk adenoma) group combined with CRC (colorectal cancer) group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota |
Revision editor(s): Yjung24
Experiment 4
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Colorectal adenoma adenoma of large bowel,adenoma of large intestine,adenoma of the large bowel,adenoma of the large intestine,colorectal adenoma,colorectum adenoma,large bowel adenoma,large intestine adenoma,Colorectal adenoma
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HRA (high-risk adenoma)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Individuals selected from available archive of fresh-frozen stool samples with high-risk adenomas were defined as those presenting with one or more adenomas of ≥10 mm, with high-grade dysplasia or villous components regardless of polyp size, or those with three or more adenomas regardless of size, dysplasia, and villosity.
- Group 1 sample size Number of subjects in the case (exposed) group
- 63
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- sex, geographic area
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Source: Table 2
Description: Differential abundance analyses of taxa and pathways between HRA and healthy controls.
Abundance in Group 1: increased abundance in HRA (high-risk adenoma)
| NCBI | Quality Control | Links |
|---|---|---|
| Lacrimispora saccharolytica |
Experiment 5
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
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 1 name Corresponds to the case (exposed) group for case-control studies
- CRC (participants diagnosed with colorectal cancer)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- participants who were diagnosed with colorectal cancer at screening during the Norwegian Colorectal Prevention trial or by registry follow-up selected from available archive of fresh-frozen stool samples.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 22
- Group 1 sample size Number of subjects in the case (exposed) group
- 7
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- geographic area, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Source: Table 2
Description: Differential abundance analyses of taxa and pathways between CRC, HRA, and healthy controls.
Abundance in Group 1: increased abundance in CRC (participants diagnosed with colorectal cancer)
| NCBI | Quality Control | Links |
|---|---|---|
| Acidaminococcus | ||
| Acidaminococcus intestini | ||
| Coprococcus eutactus | ||
| Firmicutes bacterium CAG:95 | ||
| [Lactobacillus] rogosae | ||
| Phascolarctobacterium succinatutens |
Revision editor(s): Yjung24
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Source: Table 2
Description: Differential abundance analyses of taxa and pathways between CRC, HRA, and healthy controls.
Abundance in Group 1: decreased abundance in CRC (participants diagnosed with colorectal cancer)
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides finegoldii | ||
| Monoglobus pectinilyticus | ||
| Roseburia sp. CAG:303 | ||
| Veillonella parvula |
Revision editor(s): Yjung24
Experiment 6
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Colorectal adenoma , Colorectal cancer adenoma of large bowel,adenoma of large intestine,adenoma of the large bowel,adenoma of the large intestine,colorectal adenoma,colorectum adenoma,large bowel adenoma,large intestine adenoma,Colorectal adenoma,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 1 name Corresponds to the case (exposed) group for case-control studies
- HRA (high-risk adenoma) group combined with CRC (colorectal cancer) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Individuals selected from available archive of fresh-frozen stool samples with high-risk adenomas were defined as those presenting with one or more adenomas of ≥10 mm, with high-grade dysplasia or villous components regardless of polyp size, or those with three or more adenomas regardless of size, dysplasia, and villosity. Combined with individuals selected from available archive of fresh-frozen stool samples diagnosed with colorectal cancer at screening or by registry follow-up.
- Group 1 sample size Number of subjects in the case (exposed) group
- 25
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- sex, geographic area
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Source: Table 2
Description: Differential abundance analyses of taxa and pathways between CRC, HRA, and healthy controls.
Abundance in Group 1: increased abundance in HRA (high-risk adenoma) group combined with CRC (colorectal cancer) group
| NCBI | Quality Control | Links |
|---|---|---|
| Lacrimispora saccharolytica |
Revision editor(s): Yjung24
Experiment 7
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Time Time,time
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Colorectal cancer diagnosed at time of screening
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Colorectal cancer diagnosed during 17-year follow-up/post screening
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Diagnosed with colorectal cancer at screening in the beginning of the Norwegian Colorectal Cancer Prevention Trial
- 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
- 23
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Source: Table 2
Description: Differential abundance analyses of taxa and pathways between CRC, HRA, and healthy controls.
Abundance in Group 1: increased abundance in Colorectal cancer diagnosed during 17-year follow-up/post screening
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium | ||
| Lachnospiraceae |
Revision editor(s): Yjung24
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-24
Source: Table 2
Description: Differential abundance analyses of taxa and pathways between CRC, HRA, and healthy controls.
Abundance in Group 1: decreased abundance in Colorectal cancer diagnosed during 17-year follow-up/post screening
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospiraceae |
Revision editor(s): Yjung24
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