[Microbiome and Colorectal Cancer]

The number of colorectal cancer patients in Japan continues to rise, placing the country among the highest rates globally, surpassing even Western nations. Furthermore, the increase in colorectal cancer among younger individuals(under 50 years old)is a significant concern. This rapid rise in colorectal cancer patients cannot be explained solely by the adoption of Western lifestyles, suggesting the presence of unknown carcinogenic factors. Colibactin toxin, produced by certain gut bacteria (pks+ Escherichia coli), binds to AT-rich DNA and induces characteristic mutation patterns. An international collaborative study compared the differences in these mutation patterns across 981 colorectal cancer samples collected from 11 countries, including Japan. Surprisingly, it revealed that Japanese cases exhibited a significantly higher frequency of the colibactin toxin - induced mutation patterns(SBS88 and ID18)compared to other countries. Furthermore, SBS88 and ID18 were particularly prevalent in younger patients and notably prominent in the right colon, including the rectum. These findings suggest that interventions such as preventing infection with pks+ bacteria, eradicating them, or inhibiting the function of colibactin toxin could potentially reduce the incidence of colorectal cancer, particularly in younger patients. Such prevention is also considered likely to be effective in Japan, where infection is presumed to be highly prevalent.