Mucosal DNA and RNA virome alterations and their interactions with human RNA and microRNA transcriptomes in colorectal polyps.

Abstract

Background: Imbalance in the gut microbiome is known to play a role in colorectal cancer (CRC) development. Recent studies observed alterations in the faecal and mucosal DNA virome in CRC, but the role of mucosal virome including both DNA and RNA viruses in colorectal adenomas, the precursors to CRC, is unclear. Here, we investigated the human host transcriptome, mucosal virome and potential correlations between them in paired biopsy samples of colorectal polyps and their adjacent normal tissue.

Methods: Paired colorectal polyp and adjacent normal mucosa biopsies from the same individuals were collected from 41 patients and subjected to comprehensive multiomics profiling. Total RNA and microRNA were analysed using whole transcriptome sequencing, while virus-like particles were enriched from paired samples and profiled via shotgun metagenomic sequencing. Integrated statistical and network analyses were performed to compare expression profiles and virome composition between polyp and adjacent normal mucosa from the same individuals, and to identify host-virome associations.

Results: The host transcriptome was found to be highly altered in polyps, whereby numerous differentially expressed RNAs and microRNAs were identified compared with their paired adjacent normal mucosa from the same individuals. Pathway enrichment analysis revealed that these differentially expressed genes were enriched in metabolism and absorption, neurotransmission and cell signalling pathways. The mucosal virome was also altered in polyps, with reduced viral richness and evenness and distinct community composition compared with their paired adjacent normal mucosa from the same individuals. Poxviridae, Retroviridae and BeAn 58058 virus were enriched, whereas Caudoviricetes sp was depleted. Such mucosal virome signatures correlated with host transcriptomic signatures in polyps. Caudoviricetes sp was negatively correlated with genes involved in cancer pathways, thus is potentially CRC-protective. Conversely, Poxviridae, Retroviridae and BeAn 58058 virus were negatively correlated with genes involved in tumour suppression, thus are potentially CRC-inducing.

Conclusion: This study suggests that alterations in host transcriptomes and virome of colorectal polyps are correlated, providing a foundation for future functional studies.