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

Burns MB, Lynch J, Starr TK, Knights D, Blekhman R - Genome Med (2015)

Bottom Line: 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.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.Our results provide a starting point for future prognostic and therapeutic research with the potential to improve patient outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN USA ; Department of Ecology, Evolution, and Behavior, University of Minnesota, Minneapolis, MN USA.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Differences in bacterial and archaeal phyla within the normal and colorectal cancer microbiomes. a Stacked bar plots indicating the proportional abundances of microbial phyla that are present at ≥1 % in at least one sample. The averages across all normal samples (N) and tumor samples (T) are presented at the left. Rows are arranged as patient-matched tumor (top) and normal (bottom) pairs. Patient ID numbers are appended to the right of the row pairs. b The data in panel (a) presented as the difference in abundance (Tumor – Normal) for each phylum, sorted in the same patient order, where a value of 0 would indicate no difference. Note that the legend at the right is common to panels (a) and (b)
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Fig1: Differences in bacterial and archaeal phyla within the normal and colorectal cancer microbiomes. a Stacked bar plots indicating the proportional abundances of microbial phyla that are present at ≥1 % in at least one sample. The averages across all normal samples (N) and tumor samples (T) are presented at the left. Rows are arranged as patient-matched tumor (top) and normal (bottom) pairs. Patient ID numbers are appended to the right of the row pairs. b The data in panel (a) presented as the difference in abundance (Tumor – Normal) for each phylum, sorted in the same patient order, where a value of 0 would indicate no difference. Note that the legend at the right is common to panels (a) and (b)

Mentions: We obtained patient-matched normal and tumor colon tissue samples from the University of Minnesota Biological Materials Procurement Network (BioNet) from 44 patients (see Additional file 1 for sample information). We assessed the microbiome associated with each sample by Illumina sequencing across the V5-V6 hypervariable regions of the 16S rRNA gene (see “Methods” for details). This analysis showed variation in the bacterial phyla abundance when comparing the matched normal and tumor tissues (Fig. 1a). This variability is consistent with previous reports and demonstrates that there is indeed a cancer-associated signature in the tumor microbiome [6, 10, 16, 18, 34, 47, 48]. At the level of the phyla, each sample was dominated by Firmicutes, Bacteroidetes, and Proteobacteria. There were clear and significant changes in these phyla between the normal and cancer states, with the tumors showing an enrichment of Proteobacteria and a depletion of Firmicutes and Bacteroidetes (Fig. 1b). Also consistent with previous reports, we saw an increase in the phylum Fusobacteria in the tumor-associated microbiome (two-sided Wilcoxon signed rank test q ≤ 0.1 after false discovery rate (FDR) correction for multiple tests) [7, 10, 12, 34].Fig. 1


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

Burns MB, Lynch J, Starr TK, Knights D, Blekhman R - Genome Med (2015)

Differences in bacterial and archaeal phyla within the normal and colorectal cancer microbiomes. a Stacked bar plots indicating the proportional abundances of microbial phyla that are present at ≥1 % in at least one sample. The averages across all normal samples (N) and tumor samples (T) are presented at the left. Rows are arranged as patient-matched tumor (top) and normal (bottom) pairs. Patient ID numbers are appended to the right of the row pairs. b The data in panel (a) presented as the difference in abundance (Tumor – Normal) for each phylum, sorted in the same patient order, where a value of 0 would indicate no difference. Note that the legend at the right is common to panels (a) and (b)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4499914&req=5

Fig1: Differences in bacterial and archaeal phyla within the normal and colorectal cancer microbiomes. a Stacked bar plots indicating the proportional abundances of microbial phyla that are present at ≥1 % in at least one sample. The averages across all normal samples (N) and tumor samples (T) are presented at the left. Rows are arranged as patient-matched tumor (top) and normal (bottom) pairs. Patient ID numbers are appended to the right of the row pairs. b The data in panel (a) presented as the difference in abundance (Tumor – Normal) for each phylum, sorted in the same patient order, where a value of 0 would indicate no difference. Note that the legend at the right is common to panels (a) and (b)
Mentions: We obtained patient-matched normal and tumor colon tissue samples from the University of Minnesota Biological Materials Procurement Network (BioNet) from 44 patients (see Additional file 1 for sample information). We assessed the microbiome associated with each sample by Illumina sequencing across the V5-V6 hypervariable regions of the 16S rRNA gene (see “Methods” for details). This analysis showed variation in the bacterial phyla abundance when comparing the matched normal and tumor tissues (Fig. 1a). This variability is consistent with previous reports and demonstrates that there is indeed a cancer-associated signature in the tumor microbiome [6, 10, 16, 18, 34, 47, 48]. At the level of the phyla, each sample was dominated by Firmicutes, Bacteroidetes, and Proteobacteria. There were clear and significant changes in these phyla between the normal and cancer states, with the tumors showing an enrichment of Proteobacteria and a depletion of Firmicutes and Bacteroidetes (Fig. 1b). Also consistent with previous reports, we saw an increase in the phylum Fusobacteria in the tumor-associated microbiome (two-sided Wilcoxon signed rank test q ≤ 0.1 after false discovery rate (FDR) correction for multiple tests) [7, 10, 12, 34].Fig. 1

Bottom Line: 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.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.Our results provide a starting point for future prognostic and therapeutic research with the potential to improve patient outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN USA ; Department of Ecology, Evolution, and Behavior, University of Minnesota, Minneapolis, MN USA.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus