We are pleased to announce that Prof. Takuji Yamada from Institute of Science Tokyo, Japan will join Second Conjoint RIKEN – ISM 2026 as a speaker and give a presentation entitled “Resolving Microbial Drivers of Colorectal Cancer: From Population Signatures to Strain-level Resolution and Mutational Footprints“.

The gut microbiome has been repeatedly associated with colorectal cancer (CRC), yet identifying microbial signatures alone does not establish which bacteria actively contribute to tumorigenesis. Here, I will present our recent studies that progressively move from population-level microbiome signatures toward strain-level functional resolution and host genomic evidence of microbial exposure.

First, using integrated metagenomic, metabolomic, and quantitative PCR analyses of Japanese CRC cohorts, we identified microbial and metabolic features associated with early-onset CRC. These included disease-associated microbial species and functional factors such as virulence-related genes, highlighting the importance of resolving microbial functions beyond specieslevel associations. In particular, colibactin-producing bacteria emerged as a potential contributor to early-onset CRC.

Second, to experimentally investigate the functional consequences of strain diversity, we isolated bacterial strains from patients with early-stage CRC. Clinical isolates of CRC-associated bacteria, including Lancefieldella parvula, Schaalia odontolytica, and Solobacterium moorei, showed genomic differences from reference strains, and administration of a cocktail of patient-derived strains enhanced tumorigenesis in a CRC mouse model. These findings demonstrate that disease-associated phenotypes can depend on the specific strains present within a microbial community.

Finally, by integrating whole-genome sequencing of CRC tumors with fecal metagenomic profiles, we investigated the genomic consequences of microbial exposure in the host. Colibactin-associated mutational signatures, SBS88 and ID18, were detected as early clonal events in a substantial fraction of Japanese CRCs and were particularly prevalent in younger patients. These mutational footprints provide a historical record of microbial genotoxic activity that cannot necessarily be captured by microbiome profiling at the time of diagnosis.

Together, these studies illustrate how moving beyond population-level associations toward strain-level characterization, functional validation, and host genomic footprints can provide deeper insight into microbial contributions to colorectal carcinogenesis. Such multi-layered resolution will be essential for distinguishing microbial biomarkers from microbial drivers and for ultimately developing microbiome-based strategies for cancer prevention and intervention.

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The 2^nd RIKEN-ISM Conjoint Meeting
Tokyo Microbiota 2026
September 24-25, 2026 – The University of Tokyo, Japan
tokyo.microbiota-ism.com