IDDF2022-ABS-0177 Alterations in colorectal cancer virome and its persistence after surgery

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Background Research into the microbiota of patients with colorectal cancer (CRC) has focused predominantly on the bacteriome, with other components of the microbiota yet to be explored. Our study aims to identify alterations in the virome landscape characteristic of CRC and to examine if these changes persist after surgery. Methods Forty-nine fecal samples from 25 non-cancer (NC) individuals and 12 CRC patients, before and 6-months after surgery, were collected for analysis by bacterial 16S rRNA gene sequencing. Results There was increased virome connectivity in CRC compared to NC, suggesting an altered virome landscape in CRC (IDDF2022-ABS-0177 Figure 1A. Virus-virus correlation network. Each node represent a virus species. The edges represent correlation coefficients between viruses with blue and red indicating co-occurrence and co-exclusion, respectively, IDDF2022-ABS-0177 Figure 1B. Heatmap of SparCC correlation coefficients between viruses with at least 0.7 magnitude). Co-exclusion of dominant viruses to bacterial species that are known to be associated with healthy gut status was observed in pre-op CRC patients (IDDF2022-ABS-0177 Figure 2A. Transkingdom interaction between virus-bacteria with at least 0.75 magnitude), suggesting the possibility of virus causing changes in the bacteriome that constitutes a healthy microbiome, resulting in susceptibility to CRC. Network analysis revealed lower connectivity within virome (IDDF2022-ABS-0177 Figure 1A. Virus-virus correlation network. Each node represent a virus species. The edges represent correlation coefficients between viruses with blue and red indicating co-occurrence and co-exclusion, respectively, IDDF2022-ABS-0177 Figure 1B. Heatmap of SparCC correlation coefficients between viruses with at least 0.7 magnitude) and transkingdom (IDDF2022-ABS-0177 Figure 2A. Transkingdom interaction between virus-bacteria with at least 0.75 magnitude) interactions in NC. After surgery, the number of strong correlations decreased for transkingdom (IDDF2022-ABS-0177 Figure 2A. Transkingdom interaction between virus-bacteria with at least 0.75 magnitude) and within the bacteria (IDDF2022-ABS-0177 Figure 2B. Bacteria-bacteria correlation network. Each node represents a bacterial ASV or virus. The edges represent correlation coefficients between ASV with blue and red indicating co-occurrence and co-exclusion, respectively) and virome (IDDF2022-ABS-0177 Figure 1A. Virus-virus correlation network. Each node represent a virus species. The edges represent correlation coefficients between viruses with blue and red indicating co-occurrence and co-exclusion, respectively) networks. Though some co-occurrence patterns between dominant viruses (e.g. Enterobacteria phage, Salmonella virus) and bacteria (e.g. Anaerostipes sp.) were lost after surgery, most dysbiotic signatures still persist (IDDF2022-ABS-0177 Figure 2A. Transkingdom interaction between virus-bacteria with at least 0.75 magnitude). Conclusions Microbial signatures characteristic of CRC includes an altered virome landscape besides an altered bacterial composition. Some elements of these dysbiotic signatures persist even after surgery, suggesting possible field-change in remnant non-diseased colon. Future studies should collect microbiome data at multiple time points after surgery to examine if dysbiosis truly persists.

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