Ancient mysterious microorganisms, distinct from bacteria and viruses, are believed to have a role in colorectal cancer, challenging the notion that these microorganisms are harmless.

Life can be categorized into three domains: the first consists of single-celled bacteria, the second includes eukaryotes—multicellular organisms such as animals and plants equipped with complex cells housing nuclei and DNA.

The third domain is Archaea, comprising single-celled organisms previously mistaken for bacteria due to their lack of nuclei. Recent findings reveal that they possess some traits similar to eukaryotes, suggesting that the first eukaryotes might have originated from archaeal cells that incorporated free-living bacteria.

Our intestines harbor trillions of bacteria and viruses linked to various conditions, including cancer, diabetes, obesity, and heart disease, alongside archaea, though the latter is often overlooked.

“Most researchers studying the human microbiome tend to overlook archaea, disregarding their potential significance,” notes Roxy Mohammadzadeh from Glaz Medical College in Austria. However, several archaea have been associated with colorectal cancer, Parkinson’s disease, infections related to gum disease, and urinary tract infections.

In pursuit of a clearer understanding, Mohammazzade and her team analyzed data from 19 clinical studies involving more than 1800 individuals.

They observed that while the link between archaea and several medical conditions is prevalent, it varies. Particularly, Methanobrevibacter smithii was notably present in individuals with colorectal cancer. This microbe significantly aids digestion by converting bacterial fermentation byproducts like hydrogen and carbon dioxide into methane.

Utilizing microbial culturing techniques, the team found M. smithii interacting with bacteria such as Bacteroides fragilis, E. coli, and Fusobacterium nucleatum.

These bacterial species have been linked to colorectal cancer; particularly, the association with F. nucleatum appears to be significant given its relationship with cancer. When M. smithii coexists with F. nucleatum, the latter produces higher amounts of succinate, a critical metabolic signaling molecule recognized for enhancing tumor invasiveness and spread potential noted in cancer studies.

“This represents the first mechanical evidence linking archaea to human diseases, particularly colorectal cancer,” states Mohamatzade.

This research reinforces earlier findings connecting M. smithii to colorectal cancer, asserting the need for further exploration to uncover the mechanisms at play and why this microorganism is prevalent in colorectal cancer patients, according to Gianmarco Piccinno from Trent University, Italy. He emphasizes that most available evidence is correlational and calls for additional studies.

“While Archaea is acknowledged as part of the human microbiota, its direct involvement in diseases remains poorly understood,” points out Sunny Wong from Nanyang Technological University in Singapore. Recent studies have also established connections between archaea and colorectal cancer. “Though they exist in fewer numbers than bacteria in the intestine, they are metabolically active, often consuming hydrogen, producing methane, and interacting with the host.”