Gut virome profiling identifies an association between temperate phages and colorectal cancer promoted by <i>Helicobacter pylori</i> infection

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While a close correlation between chronic <i>Helicobacter pylori</i> infection and CRC has been reported, the role of the virome has been overlooked. Here, we infected <i>Apc</i>-mutant mouse models and C57BL/6 mice with <i>H. pylori</i> and conducted a comprehensive metagenomics analysis of <i>H. pylori</i>-induced changes in lower gastrointestinal tract bacterial and viral communities. We observed an expansion of temperate phages in <i>H. pylori</i> infected <i>Apc</i>^{<i>+/1638N</i>} mice at the early stage of carcinogenesis. Some of the temperate phages were predicted to infect bacteria associated with CRC, including <i>Enterococcus faecalis</i>. We also observed a high prevalence of virulent genes, such as <i>flgJ</i>, <i>cwlJ</i>, and <i>sleB</i>, encoded by temperate phages. In addition, we identified phages associated with pre-onset and onset of <i>H. pylori</i>-promoted carcinogenesis. Through co-occurrence network analysis, we found strong associations between the viral and bacterial communities in infected mice before the onset of carcinogenesis. These findings suggest that the expansion of temperate phages, possibly caused by prophage induction triggered by <i>H. pylori</i> infection, may have contributed to the development of CRC in mice by interacting with the bacterial community.