Distinct intratumoral microbiome of young-onset and average-onset colorectal cancer

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Barot S.V., Sangwan N., Nair K.G., Schmit S.L., Xiang S., Kamath S., Liska D., Khorana A.A.
Journal
EBioMedicine
Year
2024
Keywords:
16S, Colorectal cancer, Dysbiosis, Early-onset, Microbiome, Young-onset
BACKGROUND: The unexplained rise of young-onset CRC (yoCRC, age <50 years) is of concern. Evidence suggests that microbial dysbiosis may be a contributing factor, but the tumor microbial profile of yoCRC in comparison to average-onset CRC (aoCRC, age >60) has not been fully investigated. METHODS: 16S rRNA amplicon sequencing was performed in tumor and paired adjacent non-malignant fresh frozen tissue specimens prospectively collected from 136 yoCRC and 140 aoCRC patients. Phyloseq, microbiomeSeq, metagenomeSeq, and NetComi were utilized for bioinformatics analysis. Statistical tests included Fisher's exact test, ANOVA, PERMANOVA with Bonferroni correction, linear regression, and Wilcoxon test. p-value <0.05 was considered statistically significant. FINDINGS: yoCRC patients were more likely to have left-sided (72.8 vs. 54.3%), rectal (36.7% vs. 25%), and stage IV (28% vs. 15%) tumors. yoCRC tumors had significantly higher microbial alpha diversity (p = 1.5 × 10-5) and varied beta diversity (R2 = 0.31, p = 0.013) than aoCRC tumors. yoCRC tumors were enriched with Akkermansia and Bacteroides, whereas aoCRC tumors showed greater relative abundances of Bacillus, Staphylococcus, Listeria, Enterococcus, Pseudomonas, Fusobacterium, and Escherichia/Shigella. Akkermansia had a predominantly negative correlation with the microbial communities in yoCRC tumors. yoCRC and aoCRC tumors had distinct microbial profiles associated with tumor location, sidedness, stage, and obesity. Fusobacterium (R2 = -0.23, p = 0.001) and Akkermansia (R2 = 0.05, p = 0.001) abundance correlated with overall survival in yoCRC. INTERPRETATION: Our study provides a comprehensive understanding of the microbial perturbations in yoCRC tumors. We identify microbial candidates that may highlight a distinct pathogenesis of yoCRC and serve as preventive, diagnostic, and therapeutic targets. FUNDING: Sondra and Stephen Hardis Chair in Oncology Research (A.A.K.).

Experiment 1


Needs review

Curated date: 2025/10/14

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Subjects

Location of subjects
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
Colorectum Colorectum,colorectum
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
Average-Onset Colorectal Cancer(aoCRC)(tumor tissue)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Young-Onset Colorectal Cancer(yoCRC)(tumor tissue)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Tumor tissue of patients diagnosed with colorectal cancer before the age of 50 years
Group 0 sample size Number of subjects in the control (unexposed) group
140
Group 1 sample size Number of subjects in the case (exposed) group
136

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
Random Forest Analysis
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
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
race, sex, smoking status, Confounders controlled for: "aspirin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.aspirin use, Confounders controlled for: "tumor location" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.tumor location, Confounders controlled for: "tumor stage" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.tumor stage, Confounders controlled for: "neoadjuvant treatment" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.neoadjuvant treatment

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2025/10/14

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Table 2

Description: Relative abundance (%) between yoCRC and aoCRC tumor tissue

Abundance in Group 1: increased abundance in Young-Onset Colorectal Cancer(yoCRC)(tumor tissue)

NCBI Quality ControlLinks
Akkermansia
Bacteroides

Revision editor(s): Adenike Awotunde

Signature 2

Needs review

Curated date: 2025/10/14

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Table 2

Description: Relative abundance (%) between yoCRC and aoCRC tumor tissue.

Abundance in Group 1: decreased abundance in Young-Onset Colorectal Cancer(yoCRC)(tumor tissue)

NCBI Quality ControlLinks
Bacillus
Enterococcus
Escherichia/Shigella sp.
Fusobacterium
Lactobacillus
Listeria
Parabacteroides
Pseudomonas
Salmonella
Staphylococcus
Alistipes

Revision editor(s): Adenike Awotunde

Experiment 2


Needs review

Curated date: 2025/10/15

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Average-Onset Colorectal Cancer(aoCRC)(Adjacent non-malignant tissue)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Young-Onset Colorectal Cancer(yoCRC) (Adjacent non-malignant tissue)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Adjacent non malignant(normal) tissue of patients diagnosed with colorectal cancer before the age of 50 years.

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2025/10/15

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Table 2

Description: Relative abundance (%) between yoCRC and aoCRC adjacent non-malignant tissue.

Abundance in Group 1: increased abundance in Young-Onset Colorectal Cancer(yoCRC) (Adjacent non-malignant tissue)

NCBI Quality ControlLinks
Bacteroides

Revision editor(s): Adenike Awotunde

Signature 2

Needs review

Curated date: 2025/10/15

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Table 2

Description: Relative abundance (%) between yoCRC and aoCRC adjacent non-malignant tissue.

Abundance in Group 1: decreased abundance in Young-Onset Colorectal Cancer(yoCRC) (Adjacent non-malignant tissue)

NCBI Quality ControlLinks
Akkermansia
Alistipes
Bacillus
Enterococcus
Escherichia/Shigella sp.
Fusobacterium
Lactobacillus
Listeria
Parabacteroides
Pseudomonas
Salmonella
Staphylococcus

Revision editor(s): Adenike Awotunde

Experiment 3


Needs review

Curated date: 2025/10/20

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Small-sized colorectal cancer tumors
Group 1 name Corresponds to the case (exposed) group for case-control studies
Large-sized colorectal cancer tumors
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Tumor samples from patients whose colorectal tumors are classified as large in size
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical Analysis

Statistical test
Linear Regression

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2025/10/20

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Figure 4A

Description: Correlation analysis of yoCRC and aoCRC tumors depicting the linear association between specific microbial genera and tumor size

Abundance in Group 1: increased abundance in Large-sized colorectal cancer tumors

NCBI Quality ControlLinks
Fusobacterium

Revision editor(s): Adenike Awotunde

Signature 2

Needs review

Curated date: 2025/10/20

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Figure 4A

Description: Correlation analysis of yoCRC and aoCRC tumors depicting the linear association between specific microbial genera and tumor size

Abundance in Group 1: decreased abundance in Large-sized colorectal cancer tumors

NCBI Quality ControlLinks
Akkermansia

Revision editor(s): Adenike Awotunde

Experiment 4


Needs review

Curated date: 2025/10/20

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Short overall survival in yoCRC
Group 1 name Corresponds to the case (exposed) group for case-control studies
Long overall survival in yoCRC
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Young-onset colorectal cancer patients with longer overall survival.

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
log transformation

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2025/10/20

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Figure 4B

Description: Correlation analysis of yoCRC tumors depicting the linear association between specific microbial genera and overall survival

Abundance in Group 1: increased abundance in Long overall survival in yoCRC

NCBI Quality ControlLinks
Akkermansia

Revision editor(s): Adenike Awotunde

Signature 2

Needs review

Curated date: 2025/10/21

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Figure 4B

Description: Correlation analysis of yoCRC tumors depicting the linear association between specific microbial genera and overall survival.

Abundance in Group 1: decreased abundance in Long overall survival in yoCRC

NCBI Quality ControlLinks
Fusobacterium

Revision editor(s): Adenike Awotunde

Experiment 5


Needs review

Curated date: 2025/10/21

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Colon tumors in yoCRC patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Rectal tumors in yoCRC patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rectal tumors in patients with Young-onset colorectal cancer.

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2025/10/21

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Supplemental Table S1

Description: Microbial taxa associated with tumor location in yoCRC, comparing rectal and colon tumors, showing a positive correlation between Fusobacterium abundance and rectal tumors, and a negative correlation between Akkermansia abundance and rectal tumors.

Abundance in Group 1: increased abundance in Rectal tumors in yoCRC patients

NCBI Quality ControlLinks
Fusobacterium

Revision editor(s): Adenike Awotunde

Signature 2

Needs review

Curated date: 2025/10/21

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Supplemental Table S1

Description: Microbial taxa associated with tumor location in yoCRC, comparing rectal and colon tumors, showing a positive correlation between Fusobacterium abundance and rectal tumors, and a negative correlation between Akkermansia abundance and rectal tumors.

Abundance in Group 1: decreased abundance in Rectal tumors in yoCRC patients

NCBI Quality ControlLinks
Akkermansia

Revision editor(s): Adenike Awotunde

Experiment 6


Needs review

Curated date: 2025/10/21

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Colon tumors in aoCRC patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Rectal tumors in aoCRC patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rectal tumors in patients with Average-onset colorectal cancer

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2025/10/21

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Supplemental Table S1

Description: Microbial taxa associated with tumor location in aoCRC, comparing rectal and colon tumors, showing a positive correlation between Fusobacterium abundance and rectal tumors, and a negative correlation between Akkermansia abundance and rectal tumors.

Abundance in Group 1: increased abundance in Rectal tumors in aoCRC patients

NCBI Quality ControlLinks
Fusobacterium

Revision editor(s): Adenike Awotunde

Signature 2

Needs review

Curated date: 2025/10/21

Curator: Adenike Awotunde

Revision editor(s): Adenike Awotunde

Source: Supplemental Table S1

Description: Microbial taxa associated with tumor location in aoCRC, comparing rectal and colon tumors, showing a positive correlation between Fusobacterium abundance and rectal tumors, and a negative correlation between Akkermansia abundance and rectal tumors.

Abundance in Group 1: decreased abundance in Rectal tumors in aoCRC patients

NCBI Quality ControlLinks
Akkermansia

Revision editor(s): Adenike Awotunde