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.