Altered virome structrue and function characterization in Helicobacter pylori-driven colorectal carcinogenesis and H. pylori eradication

Abstract

AbstractThe understanding of gut virome and its role in Helicobacter pylori-driven colorectal cancer (CRC), as well as the long-term impact of H. pylori eradication via antibiotic treatment on it could contribute to better understanding the mechanisms of the disruption of gut bacteriome homeostasis involved in H. pylori-driven colorectal carcinogenesis and antibiotic therapy for H. pylori eradication. In the dynamic analysis of viral genome shotgun metagenomic of samples from lower gastrointestinal tract of the Apc+/1638N and C57BL/6 mice with H. pylori infection and eradication, stable viral abundance and replacement of bursted unique viral contigs in infected and uninfected Apc+/1638N mice were observed. Temperate phages, which encoding comprehensive microbial functional genes and targeting various susceptible hosts, were expanded extremely prior to cancer exacerbation. In addition, short-term antibiotic exposure for H. pylori eradication was able to alter the gut virome and thrive the antibiotic resistance genes (ARGs) in the viral genome for at least 6 months. Collectively, these results point toward a potential role of the altered, but dynamically balanced gut virome, characterized by the expanded temperate phages, in contributing to the H. pylori-driven CRC, and indicate that viral genome may act as ARG reservoir for the antibiotic resistance of bacteria after the antibiotics therapy to H. pylori eradication.