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. 2024 May 18;16(10):1923.
doi: 10.3390/cancers16101923.

Exploring Gut Microbiome Composition and Circulating Microbial DNA Fragments in Patients with Stage II/III Colorectal Cancer: A Comprehensive Analysis

Ippokratis Messaritakis  1 , Andreas Koulouris  1 , Eleni Boukla  1 , Konstantinos Vogiatzoglou  1 , Ilias Lagkouvardos  2 , Evangelia Intze  2 , Maria Sfakianaki  1 , Maria Chondrozoumaki  1 , Michaela Karagianni  1 , Elias Athanasakis  3 , Evangelos Xynos  4 , John Tsiaoussis  5 , Manousos Christodoulakis  6 , Matthaios E Flamourakis  6 , Eleni S Tsagkataki  6 , Linda Giannikaki  7 , Evdoxia Chliara  7 , Dimitrios Mavroudis  1   8 , Maria Tzardi  9 , John Souglakos  1   8
Affiliations

Exploring Gut Microbiome Composition and Circulating Microbial DNA Fragments in Patients with Stage II/III Colorectal Cancer: A Comprehensive Analysis

Ippokratis Messaritakis et al. Cancers (Basel). .

Abstract

Background: Colorectal cancer (CRC) significantly contributes to cancer-related mortality, necessitating the exploration of prognostic factors beyond TNM staging. This study investigates the composition of the gut microbiome and microbial DNA fragments in stage II/III CRC.

Methods: A cohort of 142 patients with stage II/III CRC and 91 healthy controls underwent comprehensive microbiome analysis. Fecal samples were collected for 16S rRNA sequencing, and blood samples were tested for the presence of microbial DNA fragments. De novo clustering analysis categorized individuals based on their microbial profiles. Alpha and beta diversity metrics were calculated, and taxonomic profiling was conducted.

Results: Patients with CRC exhibited distinct microbial composition compared to controls. Beta diversity analysis confirmed CRC-specific microbial profiles. Taxonomic profiling revealed unique taxonomies in the patient cohort. De novo clustering separated individuals into distinct groups, with specific microbial DNA fragment detection associated with certain patient clusters.

Conclusions: The gut microbiota can differentiate patients with CRC from healthy individuals. Detecting microbial DNA fragments in the bloodstream may be linked to CRC prognosis. These findings suggest that the gut microbiome could serve as a prognostic factor in stage II/III CRC. Identifying specific microbial markers associated with CRC prognosis has potential clinical implications, including personalized treatment strategies and reduced healthcare costs. Further research is needed to validate these findings and uncover underlying mechanisms.

Keywords: colorectal cancer; gut microbiome; microbial DNA fragments; microbial dysbiosis; prognostic markers.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Multi-dimensional scaling (MDS) of patients (red) and healthy (blue) individuals.
Figure 2
Figure 2
Phylogram presents the sample construction via hierarchical clustering.
Figure 3
Figure 3
Taxonomic profile representing the cumulative relative abundance (%) at the family level for both patients and healthy controls.
Figure 4
Figure 4
Multi-dimensional scaling (MDS) presenting the groups that have formed the de novo clustering of the reference (control—green) and the test (patients—orange) samples.
Figure 5
Figure 5
Boxplots demonstrate the distribution of the distances from their nearest reference medoid. Each column represents the cluster that has been derived from the de novo clustering of the reference (green) and test samples (orange).
Figure 6
Figure 6
Taxonomic profile representing the cumulative relative abundance (%) at the family level for both patient and healthy control subgroups following de novo clustering.
Figure 7
Figure 7
Boxplots demonstrate the relative abundances of microbial taxa that present differences among patient clusters.
Figure 8
Figure 8
Boxplots demonstrate the effective richness and the relative abundances of microbial taxa that present differences among patients and reference controls.
Figure 9
Figure 9
Samples with an abundance of the specific zOTUs exceeding 0.25% are depicted in green color. The samples are grouped according to the clusters they belong to. The prevalence of the zOTUs in the clusters is presented in the top right of the plot. The table at the bottom displays the top hit of the zOTUs at the species level, based on the taxonomic classification of the EzBioCloud database.
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