Search

PURPOSE: There is potential for faecal microbiome profiling to improve CRC screening. This has been demonstrated by research studies, but it has not been quantified at scale using samples collected and processed routinely by a national screening programme. EXPERIMENTAL DESIGN: Between 2016-2019, the largest of the NHS Bowel Cancer Screening Programme (NHSBCSP) hubs prospectively collected processed gFOBT with subsequent colonoscopy-outcomes: blood-negative (n=491 (22%)); CRC (n=430 (19%)); adenoma (n=665 (30%)); colonoscopy-normal (n=300 (13%)); non-neoplastic (n=366 (16%)). Samples were transported and stored at room temperature. DNA underwent 16S rRNA gene V4 amplicon sequencing. Taxonomic profiling was performed to provide features for classification via random forests (RFs). RESULTS: Samples provided 16S amplicon-based microbial profiles, which confirmed previously described CRC-microbiome associations. Microbiome-based RF models showed potential as a first-tier screen, distinguishing CRC or neoplasm (CRC or adenoma) from blood-negative with AUC 0.86 (0.82-0.89) and AUC 0.78 (0.74-0.82), respectively. Microbiome-based models also showed potential as a second-tier screen, distinguishing from among gFOBT blood-positive samples, CRC or neoplasm from colonoscopy-normal with AUC 0.79 (0.74-0.83) and AUC 0.73 (0.68-0.77), respectively. Models remained robust when restricted to fifteen taxa, and performed similarly during external validation with metagenomic datasets. CONCLUSIONS: Microbiome features can be assessed using gFOBT samples collected and processed routinely by a national CRC screening programme to improve accuracy as a first or second-tier screen. The models required as few as fifteen taxa, raising the potential of an inexpensive qPCR test. This could reduce the number of colonoscopies in countries that use faecal occult blood test screening.