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Background Fecal immunochemical test (FIT) based colorectal cancer screening has limited sensitivity for advanced colorectal neoplasia. We compared its diagnostic performance with a stool-based bacterial gene marker panel (M3).Methods This investigator-initiated, international, multicenter, prospective study ( NCT05405673) included adult participants from six centers in the Asia-Pacific region who underwent colonoscopies for screening, surveillance, or diagnostic purposes. Baseline data and stool samples were collected before bowel preparation, with antibiotics and probiotics prohibited. Colonoscopy findings were confirmed by histopathology evaluated by independent pathologists. Quantitative FIT was performed in local centers, while preserved stool samples were sent to a centralized laboratory for microbiological analysis. The relative abundances of four bacterial gene markers– Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Clostridium hathewayi (Ch), and Lachnoclostridium (m3) were measured using quantitative PCR. The M3 test was a combined risk score with four bacterial gene markers and FIT using logistic regression. The primary outcome was the sensitivity of the M3 test compared with FIT in detecting advanced colorectal neoplasia, defined as CRC or advanced adenoma (AA).Results Between June 2022 and December 2025, 2,575 participants were recruited, of whom 2,108 (81.8%) were included in the analysis. There were 72 (3.4%) CRC, 178 (8.4%) AA, 758 (36.0%) non-advanced adenoma (NAA), and 1,100 (52.2%) normal or non-neoplastic findings ( IDDF2026-ABS-0439 Figure 1). The M3 test showed a higher sensitivity than FIT (55.2% vs. 45.2%, difference 10.0%, 95% confidence interval [CI] 6.3–13.7, p<0.001) in detecting advanced colorectal neoplasia, at a specificity of 85.3% (95% CI, 83.7%–86.9%). In subgroup analysis, the M3 test was more sensitive than FIT in detecting advanced neoplasia ≤20 mm, in both proximal (36.1% vs. 26.5%, difference 9.6%, 95% CI 3.3–16.0, p=0.013) and distal colon (50.0% vs. 37.8%, difference 12.2%, 95% CI 5.5–19.0, p=0.003) (IDDF2026-ABS-0439 Figure 2).Conclusions A stool-based combined panel of bacterial gene markers and FIT (M3) was more sensitive than FIT alone for advanced colorectal neoplasia detection in a multi-ethnic Asia-Pacific cohort. M3 has the potential to serve as a non-invasive screening tool that improves the detection of advanced colorectal neoplasia.Abstract IDDF2026-ABS-0439 Figure 1Abstract IDDF2026-ABS-0439 Figure 2