Clinical strains isolated from early-stage colorectal cancer patients promote tumorigenesis

Background Colorectal cancer (CRC) is prevalent worldwide and is associated with gut commensals. Recent studies have highlighted the effects of gut microbes on CRC development driven by their strain diversity. Nevertheless, the impact of the gut microbial community on tumorigenesis in early-stage (ES) CRC remains unexplored. Methods To assess the potential gut microbial community, which is critical to tumorigenesis in early-stage CRC, we collected publicly available shotgun metagenomes from CRC patient faecal samples from a Japanese population. Correlation analysis of the microbial profiles derived from the metagenomes revealed an ES CRC-associated community. To elucidate the strain diversity of the targeted community, we isolated strains from ES CRC patient faecal samples and employed comparative genomics. To evaluate the strain-specific effects of the community on tumorigenesis, we introduced an isolated strain cocktail into a CRC mouse model. Results Among the most significant ES CRC-associated species, we identified Lancefieldella parvula (Lp), as reported in a previous study. The 20 species were identified as positively correlated with Lp. Seven of the 20 species were associated with ES CRC, including Actinomyces and Solobacterium . Schaalia odontolytica (So) (formerly known as Actinomyces odontolyticus) and Solobacterium moorei (Sm) were previously reported as potential species that promote CRC. Thus, we isolated clinical strains of Lp, So, and Sm from faecal samples as potential members of the ES CRC-associated community. Comparative genomics revealed that iron-related genes were shared among clinical strains. In the oral challenge with clinical strains, namely, Lp, So, and Sm, the mice exhibited shorter survival and significantly increased tumorigenesis, suggesting that the cocktail of clinical strains is more pathogenic to the CRC mouse model than the type strain is. In summary, we inferred that the ES CRC-associated community could promote CRC, and the effects depend on the strains involved.