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Towards a Diagnostic Test for Colorectal Cancer

Cancer cells floating in pink space.
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An international team of researchers, led by the University of Trento, has identified specific groups of microbes that consistently appears in higher levels in the gut microbiome of individuals with colorectal cancer.


The findings, published in Nature Medicine, suggest this microbial signature could form the basis of a non-invasive screening test, potentially supporting earlier detection of the disease.

Identifying microbes linked to colorectal cancer

The study found around a dozen bacterial species that were significantly more abundant in stool samples from people with colorectal cancer. These included Fusobacterium nucleatum, Parvimonas micra, Gemella morbillorum and Peptostreptococcus stomatis. Several of these bacteria are typically found in the oral cavity but were consistently present in the gut microbiomes of individuals with cancer.


"We think that probably, for reasons not fully known yet, these species are able to colonize the so-called ‘tumor microenvironment’ in the guts of patients with colorectal cancer," said project head Nicola Segata, PhD, a professor and principal investigator at the University of Trento's Centre for Integrative Biology (CIBIO).  "These bacteria are normally found in the mouth of healthy individuals, but we find them in sequenced stool samples (that reflect the composition of the gut microbiome) almost only belonging to individuals with colorectal cancer."


This "microbial signature"  as the researchers termed it  was associated not only with the presence of colorectal cancer, but also with its clinical stage and anatomical location, suggesting it could offer insight into disease progression. The researchers used gut metagenomics, a technique that analyzes genetic material from microbial communities, to identify the bacterial patterns.

Machine learning supports diagnostic accuracy

To identify predictive patterns in the microbial data, the team employed a machine learning model trained on samples collected from diverse geographic locations. The model reportedly achieved nearly 90% accuracy in distinguishing individuals with colorectal cancer from those without.


"This technology, applied to the metagenomic analysis approaches that we use in our laboratory, provides a predictive model that says if there is a high probability or not that a person has colorectal cancer," said Segata.


While the study emphasizes diagnostic potential, it does not establish a causal relationship between these microbes and the development of cancer. The findings are intended to enhance early detection strategies rather than explain cancer onset.


"Whether or not the microbiome in the tumor is a cause of the tumor is almost indifferent if the primary objective is to develop a screening approach for individuals in the general population," added first author Gianmarco Piccinno, a postdoctoral researcher at CIBIO. 


The definitive clinical and preventive value of this metagenomic test remains to be verified via future registered clinical trials. However, if validated, these results could contain enough information to be used as an important additional form of screening. This would allow for a more targeted use of colonoscopy, which remains the necessary examination for a final diagnosis.

Broader research efforts and sample diversity

The researchers analyzed over 3,700 stool samples collected from 18 separate studies across nearly all continents, with the exception of Africa, South America, and Oceania. The data were gathered through large-scale collaborations, including the European Commission-funded ONCOBIOME initiative and the Cancer Grand Challenges teams PROSPECT and OPTIMISTICC.


This broad data set allowed for testing the microbial signature across populations with varying diets, lifestyles, and environmental exposures, helping to assess the robustness of the predictive model.


The research is part of ongoing global efforts to investigate the gut microbiome’s role in cancer. ONCOBIOME also explores how microbial communities might influence cancer treatment, particularly immunotherapy for conditions such as metastatic melanoma and small cell lung cancer.


The role of the microbiome in cancer remains incompletely understood. While some bacterial species are known to produce toxins that damage DNA, the overall contribution of gut microbes to cancer development continues to be studied.


Reference: Piccinno G, Thompson KN, Manghi P, et al. Pooled analysis of 3,741 stool metagenomes from 18 cohorts for cross-stage and strain-level reproducible microbial biomarkers of colorectal cancer. Nat Med. 2025. doi: 10.1038/s41591-025-03693-9


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