New research decodes the bacterial “zip code” of colorectal cancer for prediction and survival

A recent study shows that bacteria living inside colorectal tumors form distinct ecosystems that are closely linked to how the disease progression and patient outcomes. These “tissue-resident” microbes appear to play an integral role in shaping tumor biology, and can help predict patient survival more accurately than standard clinical factors alone.

The research was conducted by scientists from BGI Genomics in collaboration with Uppsala University, Umeå University, and KTH Royal Institute of Technology. It was published in Nature Communications in early December 2025.

By analyzing nearly 1,000 colorectal cancer samples, the researchers identified specific microbial patterns associated with tumor location, genetic features, and patient outcomes. They also developed a new Microbial Risk Score (MRS) based on these patterns, offering a practical way to translate complex microbiome data into prognostic insight.

This work builds on a long-term collaboration between BGI Genomics and the U-CAN research network in Sweden. A previous study from the same team, published in Nature last year, established a comprehensive genomic framework for colorectal cancer using large-scale whole-genome and transcriptome sequencing. The new research extends this framework by adding a critical new dimension -the systematic characterization of tissue-resident microbes- providing deeper insight into the complex biological landscape of colorectal cancer.

 

Microbial Communities Differ Left to Right

One of the most striking findings is that the tumor's anatomic location has a significant impact on its microbiome. Cancers arising on the right and left sides of the colon host markedly different microbial communities.

Right-sided tumors were dominated by Firmicutes bacteria, including families such as Lachnospiraceae (for example, Blautia) and Ruminococcaceae (including Faecalibacterium). These tumors contained large numbers of bacteria but showed lower overall microbial diversity.

Left-sided and rectal tumors, in contrast, supported more diverse communities with lower bacterial abundance. These sites were enriched for microbes such as Escherichia coli (E.coli), Akkermansia muciniphila, and Porphyromonas species.

The difference between tumor tissues and their nearby normal tissues was especially pronounced in the right colon. Certain cancer-associated bacteria, including specific subspecies of Fusobacterium nucleatum, were consistently enriched in tumors regardless of their location.

These microbial “signatures” were validated across independent patient cohorts. Using machine-learning models, the researchers were able to accurately predict whether a tumor originated from the right or left side of the colon based solely on its microbiome. Right-sided microbial profiles were also linked to hypoxia-related pathways, suggesting that low-oxygen conditions within tumors help select for specific bacteria, which may in turn influence tumor behavior.

 

Microbes Change Tumor Genetics

The study also found a strong link between tumor-resident microbes and the genetic landscape of colorectal cancer.

Tumors with a high number of genetic mutations—more common in the right colon - harbored distinct microbial communities enriched for oral-derived bacteria. These included multiple subspecies of Fusobacterium nucleatum and microbes such as Treponema.

Tumors with fewer mutations showed a different pattern. These cancers more frequently hosted E. coli, including strains carrying the DNA-damaging pks genomic island. These bacteria were linked to specific mutational patterns and were more common in left-sided tumors.

Importantly, the researchers observed that microbial disruption itself is a defining feature of colorectal cancer. Across genetic subtypes, tumors were consistently enriched for pathogenic bacteria compared with adjacent normal tissue. This suggests that microbial imbalance is not simply a by-product of genetic changes, but a core component of tumor development.

 

Bacteria Indicate Subtype-Specific Tumor Behavior

When tumors were stratified by established molecular subtypes, the prognostic significance of specific microbes became even clearer.

In CMS2 tumors—a subtype more often found in left-sided cancers and younger patients—high levels of Enterobacteriaceae, particularly pks-positive E. coli, were strongly associated with poorer survival. These tumors also showed signs of increased hypoxia.

In contrast, in the CMS4 subtype, elevated levels of Fusobacterium were linked to worse outcomes. These tumors exhibited a weakened anti-tumor immune response, including reduced activity of CD8-positive T cells.

These findings show that the impact of a given bacterium depends on the molecular subtype and microenvironment of the tumor. The same microbe can signal very different biological behavior depending on where and how it operates.

 

Microbial Risk Score With Clinical Potential

The most immediately actionable outcome of the study is the Microbial Risk Score.

By combining both high-risk bacteria (such as certain Clostridium species) and protective ones (including Faecalibacterium prausnitzii), the Microbial Risk Score independently predicted patient survival. In multiple analyses, it improved prognostic accuracy beyond standard factors such as age, tumor stage, and cancer genetics. Protective microbial profiles were linked to reduced inflammatory signaling, while high-risk profiles aligned with pathways known to promote cancer progression.

One notable finding was that Akkermansia muciniphila, often considered a beneficial bacterium, was associated with worse survival when present at high levels in tissue adjacent to tumors. This highlights the context-dependent role of microbes in cancer.

Together, these findings shift the view of colorectal cancer from a disease driven solely by human cells to one fundamentally shaped by interactions between human genetics and tumor-resident microbes. By decoding microbial “zip codes” within tumors, the study adds a new layer of biological insight and opens the door to more personalized prognostic assessment.

While microbiome-based treatments are not yet within reach, tumor-resident microbes are emerging as meaningful biomarkers and potential future targets. As genomic and microbial data continue to converge, understanding cancer may increasingly require looking beyond tumor genes alone to the complex microbial ecosystems that surround and interact with them.

 

About BGI Genomics

BGI Genomics, headquartered in Shenzhen, China, is the world's leading integrated solutions provider of precision medicine. Our services cover more than 100 countries and regions, involving more than 2,300 medical institutions. In July 2017, as a subsidiary of BGI Group, BGI Genomics (300676.SZ) was officially listed on the Shenzhen Stock Exchange.

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