Stool-based microbial test transforms colon cancer detection

A stool-based microbial diagnostic test outperforms faecal immunochemical test (FIT) in detecting colorectal cancer (CRC) or advanced adenoma (polyps) in a study conducted in Hong Kong, Singapore and Japan.

Dr James East

Early detection saves lives

According to Cancer Statistics 2025, CRC is the second leading cause of death in patients aged <50 years in the US. [CA Cancer J Clin 2025;75:10-45]

“However, this outcome is preventable,” said Dr James East of the University of Oxford, UK. “Since the 1970s, we have learnt that CRC develops from polyps through stepwise accumulation of genetic mutations over 10⁠–15 years.” Flexible sigmoidoscopy screening significantly reduces CRC-related mortality (hazard ratio, 0.69; 95 percent confidence interval, 0.59–0.82; p<0.001) vs control. [Lancet 2010;375:1624-1633; Cancer 1975;36:2251-2270]

FIT vs colonoscopy

In the recent SCREESCO trial, participation in CRC screening was higher among individuals invited to FIT than those invited to colonoscopy (35 vs 55 percent). “These results indicate that people generally dislike colonoscopy,” noted East. “However, the strength of evidence for FIT was limited, while that for colonoscopy is sufficient.” [Lancet Gastroenterol Hepatol 2022;7:513-521]

Stool-based microbial test superior to FIT

A noninvasive stool-based microbial test using FIT and a novel panel of bacterial gene markers – Fn, Ch, Bc, and Lachnoclostrium sp (m3) – has been developed by researchers from the Chinese University of Hong Kong. In a study involving 1,012 participants (CRC, n=274; adenoma, n=353; controls, n=385) from two independent Asian groups, the test showed a good diagnostic performance for CRC, with a specificity of 81.2 percent and a sensitivity of 93.8 percent. [Gut 2020;69:1248-1257]

According to the 2023 joint Asian Pacific Association of Gastroenterology–Asian Pacific Society of Digestive Endoscopy clinical practice guidelines, stool-based microbial biomarkers are sensitive for CRC detection and superior to tumour-based biomarkers for detection of adenomatous polyps. [Gut 2023;72:1240-1254]

The diagnostic accuracy of the stool-based microbial test was evaluated in a study conducted in Hong Kong, Singapore and Japan. Results showed a significantly higher sensitivity with the stool-based microbial test vs FIT (47.4 vs 38.9 percent; p=0.005) in detecting advanced neoplasia (ie, CRC or advanced adenoma [defined as adenoma >10 mm and/or with villous component ≥20 percent, and or harbouring high-grade dysplasia]). [Lau HS, DDW 2025]

These Asian data will be validated in a larger cohort in Oxford, London and South Tees, UK. Participant recruitment started in October 2025, and the study is expected to be completed by the end of April 2026.

What’s next?

“I expect that over the next 10 years, population screening will be based on FIT combined with other markers, such as FIT plus microbiome analysis, FIT plus methylation assays, and FIT plus polygenic risk scores,” East commented.

“Artificial intelligence [AI]–assisted colonoscopy can increase polyp detection and improve identification of serrated lesions,” he added. “Going forward, invasive colonoscopy should be therapeutic rather than merely diagnostic.”

“Patients with inflammatory bowel disease, for example, have an increased risk of CRC because of chronic intestinal inflammation. In these cases, a biomarker-driven test every 6 months may be appropriate,” East suggested.  “If the test result is positive, an AI-assisted colonoscopy should be performed.”