The human gut microbiome as a screening tool for colorectal cancer

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Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Zackular JP, Rogers MA, Ruffin MT, Schloss PD
Journal
Cancer prevention research (Philadelphia, Pa.)
Year
2014
Recent studies have suggested that the gut microbiome may be an important factor in the development of colorectal cancer. Abnormalities in the gut microbiome have been reported in patients with colorectal cancer; however, this microbial community has not been explored as a potential screen for early-stage disease. We characterized the gut microbiome in patients from three clinical groups representing the stages of colorectal cancer development: healthy, adenoma, and carcinoma. Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas. Combined with known clinical risk factors of colorectal cancer (e.g., BMI, age, race), data from the gut microbiome significantly improved the ability to differentiate between healthy, adenoma, and carcinoma clinical groups relative to risk factors alone. Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pretest to posttest probability of adenoma more than 50-fold. For example, the pretest probability in a 65-year-old was 0.17% and, after using the microbiome data, this increased to 10.67% (1 in 9 chance of having an adenoma). Taken together, the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions. Furthermore, these results support the need for more cross-sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information.

Experiment 1


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Peace Sandy

Subjects

Location of subjects
Canada
United States of America
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 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
Group 1 name Corresponds to the case (exposed) group for case-control studies
carcinoma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with colonic adenocarcinoma
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

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
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
2.5


Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2021/01/10

Curator: Lora Kasselman

Revision editor(s): WikiWorks, Peace Sandy

Source: Supplemental Figure 2 and text

Description: LeFSe analysis for healthy vs. carcinoma clinical groups. LDA values are represented for OTUs enriched in healthy and carcinoma clinical groups.

Abundance in Group 1: increased abundance in carcinoma

NCBI Quality ControlLinks
Enterobacteriaceae
Fusobacterium
Lachnospiraceae
Porphyromonas
Clostridium
Porphyromonadaceae

Revision editor(s): WikiWorks, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2021/01/10

Curator: Lora Kasselman

Revision editor(s): WikiWorks, Peace Sandy

Source: Supplemental Figure 2 and text

Description: LeFSe analysis for healthy vs. carcinoma clinical groups. LDA values are represented for OTUs enriched in healthy and carcinoma clinical groups.

Abundance in Group 1: decreased abundance in carcinoma

NCBI Quality ControlLinks
Bacteroides
Eubacteriales
Lachnospiraceae
Staphylococcus
Clostridium

Revision editor(s): WikiWorks, Peace Sandy

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2024/01/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

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
Adenoma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with colonic adenoma

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2024/01/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Supplemental Figure 1

Description: LeFSe analysis for healthy vs. adenoma clinical groups. LDA values are represented for OTUs enriched in healthy and adenoma clinical groups.

Abundance in Group 1: increased abundance in Adenoma

NCBI Quality ControlLinks
Clostridium
Porphyromonadaceae
Pseudomonas

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2024/01/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Supplemental Figure 1

Description: LeFSe analysis for healthy vs. adenoma clinical groups. LDA values are represented for OTUs enriched in healthy and adenoma clinical groups.

Abundance in Group 1: decreased abundance in Adenoma

NCBI Quality ControlLinks
Bacteroides
Clostridium
Lachnospiraceae
Odoribacter

Revision editor(s): Peace Sandy

Experiment 3


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2024/01/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Colonic lesions
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Combination of the clinical and microbiome data from adenoma and carcinoma subjects to create a combined colonic lesion group.
Group 1 sample size Number of subjects in the case (exposed) group
60

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2024/01/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Supplemental Figure 3

Description: LeFSe analysis for healthy vs. colonic lesion clinical groups. Adenoma and carcinoma clinical groups were combined into one clinical group (colonic lesion clinical group). LDA values are represented for OTUs enriched in healthy and combined colonic lesions clinical groups.

Abundance in Group 1: increased abundance in Colonic lesions

NCBI Quality ControlLinks
Porphyromonadaceae
Pseudomonas

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2024/01/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Supplemental Figure 3.

Description: LeFSe analysis for healthy vs. colonic lesion clinical groups. Adenoma and carcinoma clinical groups were combined into one clinical group (colonic lesion clinical group). LDA values are represented for OTUs enriched in healthy and combined colonic lesions clinical groups.

Abundance in Group 1: decreased abundance in Colonic lesions

NCBI Quality ControlLinks
Bacteroides
Lachnospiraceae
Clostridium

Revision editor(s): Peace Sandy

Experiment 4


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2024/01/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Adenoma
Group 1 name Corresponds to the case (exposed) group for case-control studies
Carcinoma
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with colonic adenocarcinoma
Group 1 sample size Number of subjects in the case (exposed) group
30

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2024/01/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Supplemental Figure 4.

Description: LeFSe analysis for adenoma vs. carcinoma clinical groups. LDA values are represented for OTUs enriched in adenoma and carcinoma clinical groups.

Abundance in Group 1: increased abundance in Carcinoma

NCBI Quality ControlLinks
Bacteroides
Clostridium
Fusobacterium
Parasutterella
Phascolarctobacterium
Porphyromonas

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-19

Curated date: 2024/01/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Supplemental Figure 4

Description: LeFSe analysis for adenoma vs. carcinoma clinical groups. LDA values are represented for OTUs enriched in adenoma and carcinoma clinical groups.

Abundance in Group 1: decreased abundance in Carcinoma

NCBI Quality ControlLinks
Blautia
Lachnospiraceae
Ruminococcus
Clostridium

Revision editor(s): Peace Sandy