Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment

Study information

Reviewed Marked as Reviewed by Peace Sandy on 2024-4-8

study design

meta-analysis
laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

26170900

DOI Digital object identifier for electronic documents.

10.1186/s13073-015-0177-8

URI

Authors

Burns MB, Lynch J, Starr TK, Knights D, Blekhman R

Journal

Genome medicine

Year

2015

BACKGROUND: The human gut microbiome is associated with the development of colon cancer, and recent studies have found changes in the microbiome in cancer patients compared to healthy controls. Studying the microbial communities in the tumor microenvironment may shed light on the role of host-bacteria interactions in colorectal cancer. Here, we highlight the major shifts in the colorectal tumor microbiome relative to that of matched normal colon tissue from the same individual, allowing us to survey the microbial communities in the tumor microenvironment and providing intrinsic control for environmental and host genetic effects on the microbiome. METHODS: We sequenced the microbiome in 44 primary tumor and 44 patient-matched normal colon tissue samples to determine differentially abundant microbial taxa These data were also used to functionally characterize the microbiome of the cancer and normal sample pairs and identify functional pathways enriched in the tumor-associated microbiota. RESULTS: We find that tumors harbor distinct microbial communities compared to nearby healthy tissue. Our results show increased microbial diversity in the tumor microenvironment, with changes in the abundances of commensal and pathogenic bacterial taxa, including Fusobacterium and Providencia. While Fusobacterium has previously been implicated in colorectal cancer, Providencia is a novel tumor-associated agent which has not been identified in previous studies. Additionally, we identified a clear, significant enrichment of predicted virulence-associated genes in the colorectal cancer microenvironment, likely dependent upon the genomes of Fusobacterium and Providencia. CONCLUSIONS: This work identifies bacterial taxa significantly correlated with colorectal cancer, including a novel finding of an elevated abundance of Providencia in the tumor microenvironment. We also describe the predicted metabolic pathways and enzymes differentially present in the tumor-associated microbiome, and show an enrichment of virulence-associated bacterial genes in the tumor microenvironment. This predicted virulence enrichment supports the hypothesis that the microbiome plays an active role in colorectal cancer development and/or progression. Our results provide a starting point for future prognostic and therapeutic research with the potential to improve patient outcomes.

Experiment 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-4-8

Curated date: 2024/03/17

Curator: Aananditaa

Revision editor(s): Aananditaa, Peace Sandy

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: Colon Hindgut,Large bowel,Posterior intestine,Colon,colon

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: Patient-Matched Normal Colon Tissue Samples

Group 1 name Corresponds to the case (exposed) group for case-control studies: Colorectal Tumor Samples

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: This group consists of primary tumor tissue samples obtained from patients diagnosed with colorectal cancer. They were collected from the site of tumor microenvironment.

Group 0 sample size Number of subjects in the control (unexposed) group: 44

Group 1 sample size Number of subjects in the case (exposed) group: 44

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V5-V6

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: Mann-Whitney (Wilcoxon)

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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: decreased

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: decreased

Signature 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-4-8

Curated date: 2024/03/17

Curator: Aananditaa

Revision editor(s): Aananditaa, Peace Sandy

Source: Figure 2 and 3A

Description: Differentially abundant taxa between matched normal and colorectal cancer microbiomes.

Abundance in Group 1: increased abundance in Colorectal Tumor Samples

NCBI	Quality Control	Links
Fusobacterium
Providencia

Revision editor(s): Aananditaa, Peace Sandy

Signature 2

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Reviewed Marked as Reviewed by Peace Sandy on 2024-4-8

Curated date: 2024/03/18

Curator: Aananditaa

Revision editor(s): Aananditaa

Source: Figure 2 and 3A

Description: Differentially abundant taxa between matched normal and colorectal cancer microbiomes.

Abundance in Group 1: decreased abundance in Colorectal Tumor Samples

NCBI	Quality Control	Links
Bacteroides uniformis
Faecalibacterium prausnitzii
Lachnospiraceae
Rikenellaceae
Ruminococcaceae bacterium D16

Revision editor(s): Aananditaa