How Can a Bacterium Help a Tumor Grow? The Story of Fusobacterium nucleatum

A comprehensive review published in 2025 in Signal Transduction and Targeted Therapy has drawn attention to an unexpected player in cancer biology: a bacterium called Fusobacterium nucleatum. Long recognized for its association with periodontal disease, this microorganism may play a much broader role than previously believed. After reviewing the available evidence, the authors describe how Fusobacterium nucleatum can reach certain tumors, including breast cancer, and influence their biological behavior.

The first question that naturally arises is how a bacterium that normally lives in the mouth can end up inside a tumor located elsewhere in the body. Researchers propose that during episodes of gum inflammation or minor bleeding, small numbers of bacteria may temporarily enter the bloodstream. While the immune system eliminates most of them, a few may survive long enough to reach distant tissues, including the breast.

Once Fusobacterium nucleatum reaches the tumor, it does not attach by chance. The bacterium expresses a surface protein called Fap2, which recognizes a carbohydrate molecule known as Gal-GalNAc that is highly expressed on the surface of certain cancer cells. This interaction functions as a highly specific molecular recognition system, allowing the bacterium to adhere to the tumor and establish itself within the tumor microenvironment.

According to the review, the presence of the bacterium is important not simply because it exists within the tumor, but because it can alter the tumor microenvironment. The authors describe how Fusobacterium nucleatum reduces the infiltration of T lymphocytes, the immune cells primarily responsible for recognizing and destroying cancer cells. By weakening this immune surveillance, the bacterium may create conditions that allow the tumor to grow more easily and evade the body’s natural defenses.

The review also summarizes experimental studies showing that certain microorganisms can travel inside circulating tumor cells—the cells responsible for spreading cancer to distant organs. These intracellular bacteria appear to reorganize the cytoskeleton of circulating tumor cells, helping them withstand the intense mechanical stress of blood circulation and increasing their chances of surviving long enough to establish metastatic lesions.

These findings have fundamentally changed the way scientists think about cancer. A tumor is no longer viewed simply as a collection of malignant cells. Instead, it is recognized as a complex ecosystem composed of cancer cells, blood vessels, fibroblasts, immune cells, extracellular matrix, and, in some cases, microorganisms that continuously interact with one another.

It is important to interpret these findings with caution. The review does not conclude that Fusobacterium nucleatumcauses breast cancer, nor does it suggest that periodontal disease is responsible for its development. Likewise, there is currently no evidence that antibiotics or antimicrobial therapies can prevent breast cancer or improve outcomes by eliminating this bacterium. Most of the available evidence comes from experimental studies and still requires confirmation in clinical research.

Nevertheless, the implications of this work are significant. If future clinical studies confirm these observations, understanding how Fusobacterium nucleatum interacts with cancer cells and the immune system may open entirely new therapeutic opportunities. Rather than targeting only the tumor itself, future treatments may also focus on modifying the tumor microenvironment, making it less favorable for cancer growth and metastatic spread. The story of Fusobacterium nucleatum reminds us that some of the most important advances in oncology begin with discoveries in the most unexpected places.

Reference

Xiong X, Zheng LW, Ding Y, et al. Breast Cancer: Pathogenesis and Treatments. Signal Transduction and Targeted Therapy. 2025;10:49. doi:10.1038/s41392-024-02108-4.