Gut microbiome features associated with PIK3CA-mutated colorectal cancer: A nationwide pan-cancer genomic and microbial profiling study (MONSTAR-SCREEN)
We investigated gut microbial features associated with oncogenic alterations across solid tumors, focusing on PIK3CA -mutant colorectal cancer (CRC). Fecal 16 S rRNA sequencing and comprehensive genomic profiling data from 1,414 patients in the nationwide MONSTAR-SCREEN study were analyzed after excluding antibiotic exposure within 3 months before treatment initiation. In CRC, PIK3CA -mutant cases showed lower alpha diversity than wild-type cases in both tissue-derived (10 vs. 74; P = .018, q = 0.331) and blood-derived analyses (22 vs. 199; P = .029, q = 0.441), although neither association remained significant after false discovery rate correction. In the tissue-derived cohort, several taxa showed nominally lower abundance in PIK3CA -mutant cases. Multivariable analyses adjusted for age, body mass index, PPIs, and Bristol Stool Scale showed similar directional associations, but none reached FDR-adjusted significance. PICRUSt2-based inference also identified nominally higher predicted primary and secondary bile acid biosynthesis, with the same direction observed in the MSS-restricted analysis. These exploratory findings suggest an association between PIK3CA mutation status and gut microbial features in CRC and support validation in larger cohorts using direct metagenomic and metabolomic approaches.
Authors
- Toshihiro Kudo (ORCID: https://orcid.org/0000-0003-3584-6375)
- Shunsuke A. Sakai (ORCID: https://orcid.org/0009-0002-3740-6795)
- Satoshi Horasawa (ORCID: https://orcid.org/0009-0007-0501-067X)
- Kentaro Yamazaki (ORCID: https://orcid.org/0000-0001-6269-9345)
- Hironaga Satake (ORCID: https://orcid.org/0000-0001-7629-6803)
- Shigenori Kadowaki (ORCID: https://orcid.org/0000-0001-9923-5309)
- Takao Fujisawa (ORCID: https://orcid.org/0009-0002-3438-5757)
- Tadamichi Denda (ORCID: https://orcid.org/0000-0003-2570-9692)
- Manabu Shiozawa (ORCID: https://orcid.org/0009-0006-1912-5948)
- Nobuhisa Matsuhashi (ORCID: https://orcid.org/0000-0001-5993-9571)
- Takayuki Yoshino (ORCID: https://orcid.org/0000-0002-0489-4756)
- Hisateru Yasui (ORCID: https://orcid.org/0000-0001-5563-5802)
- Naoki Takahashi (ORCID: https://orcid.org/0000-0001-6377-9507)
- Toshifumi Yamaguchi (ORCID: https://orcid.org/0000-0003-1399-1918)
- Ayumu Yoshikawa (ORCID: https://orcid.org/0009-0005-3142-6164)
- Tomohiro Nishina (ORCID: https://orcid.org/0000-0002-4073-3757)
- Riu Yamashita
- Yoshito Komatsu
- Yoshiaki Nakamura
- Shogen Boku
- Kentaro Sawada
Institutions
- Kansai Medical University (JP)
- University of Kochi (JP)
- Osaka Medical and Pharmaceutical University (JP)
- Shizuoka Cancer Center (JP)
- Kushiro Rosai Hospital (JP)
- Chiba Cancer Center (JP)
- Saitama Cancer Center (JP)
- Aichi Cancer Center (JP)
- Shikoku Cancer Center (JP)
- Hokkaido University Hospital (JP)
- National Cancer Center Hospital East (JP)
- Osaka International Cancer Institute (JP)
- Kobe City Medical Center General Hospital (JP)
- Gifu University (JP)
- Kanagawa Cancer Center
- Kōchi University (JP)
Publication Details
- Journal
- Scientific Reports
- Published
- 2026-10-04
- DOI
- https://doi.org/10.1038/s41598-026-74246-4
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Clinical Trial Center, China Medical University Hospital