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“Colon cancer ranks as the second most deadly form of cancer in the United States.”

Colorectal cancer is a major global health concern with a significant impact on mortality and morbidity. According to the American Cancer Society, colon cancer ranks as the second most deadly form of cancer in the United States, with an expected mortality of over 53,000 people in the country in 2024. A recent study published in the journal Nature by Martha Zepeda Rivera, PhD, and colleagues, from the Fred Hutchinson Cancer Center, Seattle, WA, has revealed a complex interplay between human microbiota and cancer development, specifically highlighting the role of Fusobacterium nucleatum (Fn) in colorectal cancer.

Fn, predominantly found in the oral cavity, has been discovered in higher concentrations within colorectal cancer tissues, indicating a potential role in cancer pathogenesis. Previous studies have established an association between high Fn loads within the tumor and adverse cancer outcomes. Fn’s capability to colonize tumors and colonizing metastatic sites suggest a possible mechanistic role in cancer progression.

The study aimed to identify genetic reasons why the Fn bacterium settles in colorectal cancer tumors. Researchers studied the complete genetic information of 135 samples of the Fn bacterium, taken from cancerous colon tumors and healthy people’s mouths. They compared these samples to understand the genetic features that allow Fn to thrive specifically in the environment of colorectal cancer.

“Experiments with mice showed that those infected with Fna C2 developed more tumors and showed chemical changes in their bodies related to cancer.”

The research found that the Fn bacteria linked to colorectal cancer mostly come from a subgroup named Fusobacterium nucleatum subspecies animalis (Fna). Within this subgroup, two types were discovered, Fna C1 and Fna C2, with Fna C2 being the more common type found in cancerous tumors. The study identified 195 genes unique to Fna C2, suggesting it has special abilities to adapt and thrive in the digestive tract. Experiments with mice showed that those infected with Fna C2 developed more tumors and showed chemical changes in their bodies related to cancer. Microbiome analysis of human colorectal cancer tissues and stool samples showed a higher presence of Fna C2 in cancerous tissues than in healthy tissues, confirming its strong link with colorectal cancer.

The genetic and experimental analysis highlighted Fna C2 as the main variant of Fn affecting colorectal cancer. The unique genetic traits of Fna C2, which enhance its survival and growth in the cancer environment, point to its role in the disease. These insights improve our understanding of how microbes interact with cancer and suggest new directions for treatments targeting these bacteria.

“The study illustrates a correlational relationship between Fna clade 2 and colorectal cancer.”

The study illustrates a correlational relationship between Fna clade 2 and colorectal cancer, indicating that while Fna C2 is frequently found in colorectal cancer tumors, it does not definitively establish that Fna C2 causes the cancer. The research, although thorough, points to the enrichment of Fna C2 in colorectal cancer tumors and its potential genetic adaptations for survival in such an environment yet stops short of confirming a direct causative link.

The study does have some limitations. For one, the relationship between different microbes in the colorectal cancer environment is quite complex and not fully understood. Since the pathophysiology of colorectal cancer is influenced by many factors, including genetics, diet and lifestyle, and various microbes, it’s hard to confirm one leading cause. Also, while the experiments with mice in the study provided some indications, these models cannot completely mirror the complexities of human colorectal cancer. More research is needed to determine how this bacterium interacts with our bodies and other microbes in cancer conditions. While the study gives us valuable insights into the link between Fna C2 and colorectal cancer, it also highlights the need for further detailed research to really understand this link.

Identifying Fna C2 as the leading Fusobacterium nucleatum type in colorectal cancer represents a step in microbiome and cancer research. This study lays the groundwork for future investigations into how changing the microbiome could help manage and treat colorectal cancer, opening up new avenues for microbiome-targeted therapies and prevention strategies in colorectal cancer.