Assessment of bacterial and viral gut communities in healthy and tumoral colorectal tissue usingRNAandDNAdeep sequencing

Abstract

BackgroundColorectal cancer (CRC) is known to present a distinct microbiome profile compared to healthy mucosa. Non‐targeted deep‐sequencing strategies enable nowadays full microbiome characterization up to species level.AimWe aimed to analyze both bacterial and viral communities in CRC using these strategies.Materials & MethodsWe analyzed bacterial and viral communities using both DNA and RNA deep‐sequencing (Novaseq) in colorectal tissue specimens from 10 CRC patients and 10 matched control patients. Following taxonomy classification using Kraken 2, different metrics for alpha and beta diversities as well as relative and differential abundance were calculated to compare tumoral and healthy samples.ResultsNo viral differences were identified between tissue types, but bacterial species Polynucleobacter necessarius had a highly increased presence for DNA in tumors (p = 0.001). RNA analyses showed that bacterial species Arabia massiliensis had a highly decreased transcription in tumors (p = 0.002) while Fusobacterium nucleatum transcription was highly increased in tumors (p = 0.002).DiscussionSequencing of both DNA and RNA enables a wider perspective of micriobiome profiles. Lack of RNA transcription (Polynucleobacter necessarius) casts doubt on possible role of a microorganism in CRC. The association of F. nucleatum mainly with transcription, may provide further insights on its role in CRC.ConclusionJoint assessment of the metagenome (DNA) and the metatranscriptome (RNA) at the species level provided a huge coverage for both bacteria and virus and identifies differential specific bacterial species as tumor associated.

Intestinal Dysbiosis: Microbial Imbalance Impacts on Colorectal Cancer Initiation, Progression and Disease Mitigation

“…Phages are thought to be key players in bacterial-associated carcinogenesis by modulating the microbial diversity present and CRC development [23]. One study identified four phages in increased abundance in CRC patients [88]. Cancer virotherapy is immunotherapy that uses genetically modified viruses (oncolytic viruses) to selectively target and lyse cancer cells and also facilitates the activity of immune checkpoint inhibitors, which may be beneficial in the treatment of CRC [89].…”

Gut microbiome: decision-makers in the microenvironment of colorectal cancer

“…Additionally, in a pathological context, F. nucleatum augments its virulence through the secretion of an amyloid-like adhesin called FadA, utilizing a Fap2-like autotransporter ( Meng et al., 2021 ). In addition, F. nucleatum can enhance drug resistance of tumor cells, inhibit neutrophil infiltration, and ultimately change the tumor immune microenvironment ( Alon-Maimon et al., 2022 ; Garcia-Serrano et al., 2023 ). F. nucleatum is involved in tumor initiation or progression before cancer formation, which regulating the tumor immune microenvironment and promoting the proliferation of tumor-infiltrating immune cells ( Kostic et al., 2013 ).…”