Cell & Microbiology

Microbiologists find a control system that prevents cancer-causing germs from multiplying.

Researchers at the Forsyth Institute have identified a crucial mechanism that could have significant effects on colorectal cancer prevention strategies. Strangely, it was in the mouth that they made their discovery.

Over 52,000 people per year are lost to colorectal cancer, the second-deadliest cancer. Fusobacterium nucleatum, an oral pathogen that thrives on opportunity, is one of the factors contributing to colorectal cancer, according to a growing body of evidence. Fusobacteria are frequently found in healthy mouths, where they coexist in harmony with other oral microorganisms. It is regarded as opportunistic because, under certain circumstances, it quickly gets out of control and harms the human host.

Fusobacteria were kept in check in healthy mouths for a reason, which the researchers sought to understand. They discovered that a molecule naturally produced by the human host directly targets Fusobacteria and prevents it from taking over. It’s a small RNA molecule.

“The remarkable thing about this little RNA is that it is both potent and targeted. It does not eliminate all bacteria, both healthy and bad. It exclusively works against Fusobacteria. The molecule’s capacity to target a specific disease is what makes it a prospective therapeutic agent.”

Dr. Xuesong He, a Forsyth Senior Member of Staff who led the study.

The ISME Journal article “Targeting Fusobacterium nucleatum through Chemical Modifications of Host-derived Transfer RNA Fragments,” which summarizes their findings, suggests that a chemically altered version of this molecule may one day be used as a potential therapeutic to ward off colorectal cancer.

According to Dr. Xuesong He, a Forsyth senior member of staff who oversaw the study, “This small RNA is amazing because it is very potent and very targeted. Both good and bad bacteria are not completely eliminated. Only Fusobacteria are inhibited. The molecule is a potentially effective therapeutic agent due to its capacity to target a particular pathogen.”.

Human health and disease are significantly influenced by the oral microbiome, which is made up of communities of microbes. When the harmony between the host and the bacteria is disturbed, disease results. It’s possible that some pathogenic bacteria will start to proliferate and cause issues.

How does a microbe in our mouth affect other parts of our body? Dr. Pu-Ting Dong, a Forsyth postdoctoral fellow and the co-first author of this study, explained, “In a healthy mouth with good hygiene, fusobacteria are kept in check. Fusobacteria can grow out of control in situations where the mouth’s homeostasis is disturbed by poor oral hygiene or weakened host defenses.

Periodontal disease is frequently brought on by this overgrowth of Fusobacteria. However, it can also result in more serious conditions like colorectal cancer. The bacteria can enter the bloodstream and travel to other parts of the body, such as the colon, if someone brushes and flosses infrequently and experiences microbleeds. In addition to colorectal cancers, oral health issues are also closely related to other systemic diseases like diabetes and Alzheimer’s.

In order to make the small RNA even more effective at thwarting and preventing fusobacterial overgrowth, Dr. He’s team collaborated with Dr. Jiahe Li, the co-corresponding author of this article, from Northeastern University. The Forsyth Institute and Northeastern University have submitted a PCT/US21/1990 international patent for these altered Fusobacterium-targeting small RNAs.

The goal of the researchers is to develop efficient preventative therapeutics for systemic diseases caused by Fusobacteria through their continued research in this area.

Drs. Wenyuan Shi and Lujia Cen of the Forsyth Institute, as well as Drs. Mengdi Yang of Northeastern University, were additional study participants.

More information: Mengdi Yang et al, Targeting Fusobacterium nucleatum through chemical modifications of host-derived transfer RNA fragments, The ISME Journal (2023). DOI: 10.1038/s41396-023-01398-w

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