IARC 60th Anniversary - 19-21 May 2026
Session : 19/05/26 - Posters
Microbiome signatures for detection of colorectal lesions in population-based FIT screening
BIRKELAND E. 1, ANE K. 1,2, AVERSHINA E. 1,3, BUCHER-JOHANNESSEN C. 1,3, BEMANIAN V. 8, BLIX H. 2, HJÅRTAKER A. 1, DE VOS W. 4,5, URSIN G. 1,2,6, HOFF G. 2,7, RANDEL K. 2, BOTTERI E. 2, BERSTAD P. 2, ROUNGE T. 1,2
1 University of Oslo, Oslo, Norway; 2 Norwegian Institute of Public Health, Oslo, Norway; 3 Oslo University Hospital, Oslo, Norway; 4 University of Helsinki, Helsinki, Finland; 5 Wageningen University, Wageningen, Netherlands; 6 University of Southern California, Los Angeles, United States; 7 Telemark Hospital, Skien, Norway; 8 Akershus University hospital, Lørenskog, Norway
Background: Fecal immunochemical testing (FIT) is a widely implemented colorectal cancer (CRC) screening tool; however, FIT has limited sensitivity for advanced adenomas and serrated lesions. The gut microbiome has been linked to CRC development, with microbe-based classifiers distinguishing between CRC patients and healthy controls. Understanding microbiome variation across colonoscopy-verified lesion categories within FIT-positive individuals is essential for evaluating the translational potential of microbiome-based screening augmentation. However, utility of the microbiome in screening-relevant settings remains largely uncharted.
Objectives: To investigate associations between gut microbiome composition and colorectal lesion status in a FIT-positive, population-based screening cohort, and to assess whether microbial features can improve discrimination of advanced colorectal lesions and cancer.
Methods: In a Norwegian population-based study, we used fecal immunochemical test (FIT) leftovers from 1034 FIT-positive (i.e. positive for occult blood) screening participants for gut metagenome profiling using shotgun sequencing.
This study was conducted within the CRCbiome study, nested in the Bowel Cancer Screening in Norway (BCSN) program. Participants aged 55–76 years with a positive FIT result were invited to provide a fecal sample prior to follow-up colonoscopy. Shotgun metagenomic sequencing of FIT leftover from 1034 participants was performed to generate taxonomic and functional profiles of the gut microbiome. Colonoscopy findings were classified into 1) no neoplasia, non-advanced lesions, advanced adenomas or advanced serrated lesions, and CRC or 2) with or without neoplastic findings. Associations between microbiome features and lesion categories were evaluated using diversity analyses and differential abundance testing, accounting for relevant demographic, dietary, lifestyle and clinical covariates. Machine-learning models were developed to classify neoplastic lesions using microbial features and quantitative FIT values, contrasting FIT alone.
Results: Combining microbial profiles with quantitative FIT values improved detection of premalignant lesions beyond optimizing the FIT value alone, even after incorporating established CRC risk factors. Still, the FIT value maintained superior discriminative ability for CRC. We confirmed enrichment of bacteria such as Fusobacterium nucleatum and Peptostreptococcus stomatis in CRC. In contrast, other bacteria previously associated with the presence of CRC, including Hungatella hathewayi and Clostridium symbiosum, as well as pks-negative Escherichia coli, were enriched in those with no neoplastic findings, suggesting that their presence may reflect other conditions causing colon bleeding rather than underlying neoplasia. Microbial profiles were predominantly associated with distal rather than proximal lesions.
Conclusions: Our findings highlight the potential for microbial markers to improve FIT-based CRC screening, especially by differentiating those with premalignant lesions from those who test FIT positive for other reasons.