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For years, scientists have largely overlooked a group of microorganisms residing in our guts, considering them benign bystanders in the complex world of the human microbiome. These ancient organisms, called archaea, are neither bacteria nor viruses, occupying a unique domain of life. However, mounting evidence suggests that certain archaea, particularly Methanobrevibacter smithii, may play a surprising and significant role in the development and progression of colorectal cancer.
The gut microbiome, a bustling community of trillions of bacteria, viruses, and fungi, has been linked to a variety of health conditions, including cancer, diabetes, and heart disease. While research has primarily focused on bacteria and viruses, archaea have often been disregarded. “Most scientists who are working on the human microbiome overlook archaea and totally filter out these organisms,” says Roxy Mohammadzadeh at the Medical University of Graz in Austria. This oversight is despite observations that high numbers of archaea have been found alongside conditions like colorectal cancer, Parkinson’s disease, and even gum and urinary tract infections.
Mohammadzadeh and her team recently conducted a comprehensive analysis of 19 clinical studies, encompassing data from over 1800 individuals, to investigate the potential link between gut archaea and various diseases. Their findings, published in a peer-reviewed journal, revealed a consistent pattern: individuals with colorectal cancer exhibited significantly higher levels of Methanobrevibacter smithii in their gut microbiome. This archaeon is known for its role in digestion, consuming byproducts of bacterial fermentation like hydrogen and carbon dioxide, and releasing methane as a result.
Further investigation revealed that M. smithii interacts with several bacterial species previously linked to colorectal cancer, including Bacteroides fragilis, Escherichia coli, and Fusobacterium nucleatum. The moment things shifted, researchers discovered, was the unexpected influence M. smithii had on F. nucleatum. In the presence of the archaeon, *F. nucleatum* produced substantially more succinate, a metabolic signaling molecule.
Succinate, while essential for various cellular processes, has been shown to promote tumor invasiveness and metastasis in the context of cancer. Current Observation: Succinate increase in presence of *M. smithi* in cancer cells. Underlying Implication: Promotes invasiveness and spread of tumors. Broader Context: Microbe interactions contributing to cancer development. This discovery provides a plausible mechanistic explanation for how archaea could contribute to colorectal cancer progression. “It’s the first mechanistic evidence showing the role of archaea on human disease and specifically colorectal cancer,” says Mohammadzadeh.
This research builds upon earlier correlational studies that also associated *M. smithii* with colorectal cancer, notes Gianmarco Piccinno at the University of Trento in Italy. However, he emphasizes the need for further research to fully elucidate the cancer-causing mechanisms and the reasons behind the increased abundance of this microbe in individuals with colorectal cancer. It’s imporatnt to highlight that correlation doesn’t equal causation.
- Key Findings: M. smithii consistently elevated in colorectal cancer patients.
- Mechanistic Link: M. smithii enhances succinate production by F. nucleatum, promoting tumor invasiveness.
- Research Gaps: Further studies needed to confirm causality and understand the underlying mechanisms.
- Clinical Implications: Could lead to new diagnostic and therapeutic strategies targeting gut archaea.
Sunny Wong at Nanyang Technological University in Singapore, who has also recently reported links between archaea and colorectal cancer, echoes this sentiment. “While archaea have been recognised as components of the human microbiome, their direct involvement in disease has remained poorly understood,” says Wong. He adds that despite their smaller numbers compared to bacteria in the gut, archaea are metabolically active and interact with both bacteria and the host, making them potentially significant players in health and disease. Someone with the username @GutFeeling posted on X.com: “Always knew there was more to the story than just bacteria!” This sentemnt is reflective of many peoples reactions to the findings.
The implications of this research are far-reaching. Understanding the role of archaea in colorectal cancer could open new avenues for diagnosis, prevention, and treatment. Perhaps screening for *M. smithii* levels could become a part of routine colorectal cancer screenings, particularly for individuals at high risk. Therapeutic strategies targeting the interactions between archaea and bacteria in the gut could also be developed to slow or even prevent the progression of the disease. This could entail the development of specififc drugs that inhibit archaeal growth or metabolic activity.
One of the study’s limitations is its reliance on existing datasets, says Mohammadzadeh. More studies with larger populations are needed to confirm these initial findings. In one case a data anomoly seemed to be present, but was ultimatley accounted for. “It’s like we’ve been ignoring a whole continent on the microbial map,” commented Dr. Eleanor Vance, a leading microbiome researcher at the University of California, San Diego, on her Facebook page, adding, “This research is a wake-up call.”
The journey to understanding the complex interplay between gut microbes and human health is still in its early stages. However, this latest research suggests that the often-overlooked archaea may hold vital clues to unraveling the mysteries of colorectal cancer. Further studies are now focusing on trying to replicate these finidngs across diverse populations. And it is hoped these findings will provide critical insight into the cancer-driving mechanism involved, thereby paving the way for new therapeautic intervention.
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