Prevalence and chronology of colibactin-associated mutational processes and their microbiome spectra in Japanese colorectal cancer.

Satoshi Shiba; Shinichi Yachida; Sayaka Mizutani; Yasushi Totoki; Hiromi Nakamura; Natsuko Hama; Norikatsu Miyoshi; Yasuhito Arai; Mihoko Saito-Adachi; Hirokazu Kimura; Yoshito Hayashi; Hiroyuki Takamaru; Koji Tanaka; Rie Hayashi; Hirofumi Rokutan; Shoko Ikuta; Yukihide Kanemitsu; Yuichiro Doki; Hidetoshi Eguchi; Satoshi Hattori; Yutaka Saito; Takuji Yamada; Tatsuhiro Shibata

doi:10.1038/s41588-026-02692-x

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Prevalence and chronology of colibactin-associated mutational processes and their microbiome spectra in Japanese colorectal cancer.

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Abstract

The incidence of colorectal cancer (CRC) has risen in recent decades, with a disproportionate increase observed among younger individuals in Japan and other countries. The etiological contribution of the gut microbiota to CRC pathogenesis is recognized, yet the mechanisms involved remain to be fully clarified. Here we integrated whole-genome sequencing (WGS) and transcriptome profiling of CRC with whole-genome metagenomic sequencing of fecal samples to interrogate host-microbiome interactions at high resolution. Application of interpretable artificial intelligence enabled the stratification of CRC into four distinct microbiome-informed subtypes. WGS analysis identified mutational signatures SBS88 and ID18, linked to colibactin exposure, as early clonal events detected in 44.8% of non-hypermutated patients. Notably, these signatures were significantly more frequent among patients born after the 1960s. Microbiome-based subclassification revealed subtype-specific clinical and molecular features. Collectively, our findings indicate that colibactin exposure constitutes a prevalent and potentially modifiable risk factor for CRC in the Japanese population.

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Humans Colorectal Neoplasms Japan Mutation Polyketides Peptides Whole Genome Sequencing Prevalence Female Gastrointestinal Microbiome Male Middle Aged Aged Feces Gene Expression Profiling Risk Factors East Asian People Journal Article

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Satoshi Shiba, Shinichi Yachida, Sayaka Mizutani, Yasushi Totoki, Hiromi Nakamura, Natsuko Hama, Norikatsu Miyoshi, Yasuhito Arai, Mihoko Saito-Adachi, Hirokazu Kimura, Yoshito Hayashi, Hiroyuki Takamaru, Koji Tanaka, Rie Hayashi, Hirofumi Rokutan, Shoko Ikuta, Yukihide Kanemitsu, Yuichiro Doki, Hidetoshi Eguchi, Satoshi Hattori, Yutaka Saito, Takuji Yamada, Tatsuhiro Shibata. 2026-08-10. Prevalence and chronology of colibactin-associated mutational processes and their microbiome spectra in Japanese colorectal cancer.. https://doi.org/10.1038/s41588-026-02692-x

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