New Research Shows this Microbe, Typically Thought Harmless, is Associated with Cancer

In the vast ecosystem of the microbiome in the human gut, archaea—ancient single-celled organisms— are often overlooked. While much attention has been focused on bacteria and viruses as the main constituents of the microbiome, and causal factors behind health and disease, recent studies suggest that a specific archaeon, Methanobrevibacter smithii, may be involved in colorectal cancer, a startling finding that challenges long-held assumptions about these microorganisms being harmless.

Archaea: The Forgotten Microbes

There are three fundamental domains of life: bacteria, eukaryotes (which include all animals and plants), and archaea. Archaea were once thought to be simple bacteria due to their lack of a nucleus. However, they share surprising genetic similarities with eukaryotes and are believed to be the ancestors of early eukaryotic life. These single-celled organisms are found in various environments, including the human gut, where they typically contribute to digestion by consuming products of bacterial fermentation, such as hydrogen and carbon dioxide, and releasing methane.

While bacteria and viruses in the gut have been extensively studied and linked to a range of diseases—including cancer, obesity, and heart disease—archaea have largely remained under the radar. This is beginning to change as new research uncovers their potential involvement in human diseases, including colorectal cancer.

The Discovery of Methanobrevibacter smithii

In a groundbreaking study, researchers led by Roxy Mohammadzadeh at the Medical University of Graz, Austria, examined the gut microbiome of over 1,800 individuals across 19 clinical studies. Their analysis revealed a consistent pattern: Methanobrevibacter smithii, an archaeon known for its role in methane production, was significantly more abundant in individuals with colorectal cancer.

“M. smithii plays a big role in digestion, consuming hydrogen and carbon dioxide produced by bacteria and releasing methane,” Mohammadzadeh explains. “But our research shows that this archaeon may be implicated in the development of colorectal cancer, working alongside other bacteria like Bacteroides fragilis, Escherichia coli, and Fusobacterium nucleatum—microbes already known to be linked to cancer.”

Interestingly, the most notable interaction was between M. smithii and F. nucleatum, a bacterium previously associated with colorectal cancer. In the presence of M. smithii, F. nucleatum produced higher levels of succinate, a metabolite that can enhance tumor invasiveness and facilitate its spread, offering a potential mechanism for cancer progression.

“This is the first mechanistic evidence showing how archaea, particularly M. smithii, could contribute to human disease, specifically colorectal cancer,” says Mohammadzadeh. “Our findings offer a new perspective on how microbes in the gut interact to influence disease outcomes.”

The Need for More Research

Despite the promising discoveries, researchers emphasize that more studies are needed to fully understand how M. smithii and other archaea contribute to colorectal cancer. Current evidence remains largely correlational, and it’s unclear whether M. smithii directly causes cancer or if its increased presence is merely a byproduct of the disease.

Gianmarco Piccinno, a researcher at the University of Trento in Italy, points out, “While our study adds to the body of evidence linking M. smithii to colorectal cancer, it’s important to conduct further research to determine the precise mechanisms and why people with colorectal cancer have more of this archaeon.”

Sunny Wong, a microbiologist at Nanyang Technological University in Singapore, adds, “Although archaea exist in much smaller numbers than bacteria in the gut, they are metabolically active and interact with both bacteria and the host. Their role in health and disease is more significant than we once thought.”

What Does This Mean for Colorectal Cancer Treatment?

This discovery could potentially lead to new approaches in the prevention and treatment of colorectal cancer. Targeting the gut microbiome, specifically M. smithii and its interactions with harmful bacteria, could offer a novel therapeutic strategy. However, experts caution that clinical application will require a deeper understanding of how these archaea function in disease.

“It’s still early days, but our research points to the exciting possibility of manipulating the gut microbiome to reduce cancer risk,” says Mohammadzadeh. “This could involve using specific antibiotics, probiotics, or other interventions that target M. smithii and other microbes that influence cancer development.”

Conclusion

The role of archaea in human disease, particularly colorectal cancer, is a fascinating and rapidly developing area of research. As scientists continue to uncover the complex relationships between microbes and cancer, it becomes clear that our understanding of the gut microbiome—and its influence on health—must expand beyond bacteria and viruses to include archaea. With further research, these ancient microbes may offer new insights into colorectal cancer prevention, diagnosis, and treatment.

Summary:

• Archaea—ancient, single-celled organisms—have been overlooked in microbiome studies, but recent research suggests they play a role in human diseases, including colorectal cancer.
• Methanobrevibacter smithii, an archaeon in the gut, has been consistently linked to colorectal cancer in clinical studies.
• M. smithii interacts with bacteria like Fusobacterium nucleatum to produce succinate, a metabolite that may enhance tumor invasiveness.
• Experts emphasize the need for more research to understand the exact mechanisms behind these findings.
• The discovery could lead to new strategies for preventing or treating colorectal cancer by targeting gut microbiome interactions.