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Title of the presentation: Microbiome spectra and prevalent colibactin-associated mutational process in Japanese colorectal cancer Speaker: Takuji Yamada More info on this event: https://www.microbiome-vif.org/en-US/... Join us at the next meeting (free registration!): https://www.microbiome-vif.org/ And you can join us on Twitter: / microbiomevif Abstract of this talk: The rising incidence of colorectal cancer (CRC), particularly among younger patients, has become a major public health concern in Japan and worldwide. While the association between the gut microbiota and CRC is well recognized, its molecular basis remains unclear. We aimed to clarify this relationship by integrating whole-genome sequencing (WGS) and transcriptome data from CRC tissues with whole-genome metagenomic sequencing (WGMS) of fecal samples. We applied explainable artificial intelligence (AI) analysis to classify CRC into four microbiome-based subtypes and examined their clinical and molecular characteristics. Colibactin-associated mutational signatures (SBS88 and ID18) were analyzed as potential early clonal events. One subtype was enriched in younger patients and associated with poor prognosis. WGS revealed colibactin-associated mutational signatures in 97 of 138 patients (70.3%), with a higher prevalence in the younger subtype. APC hotspot mutations and frameshift deletions matching the colibactin-specific motif were observed in 12 patients (8.7%). CRCs with colibactin signatures were characterized by an immunosuppressive tumor microenvironment. Colibactin exposure is a common yet potentially modifiable risk factor for CRC in the Japanese population. Our findings highlight the potential of microbiome-based subclassification to provide clinical and biological insights into CRC, particularly in younger patients.