Research on the genome of Fusobacterium nucleatum, which was isolated from colon cancer tumors, might aid in the development of cancer vaccines and screening tools in the future.
An optimally functioning colon is an incredible tool that extracts nutrients and water from meals while expelling waste. However, occasionally, cancer develops from tiny clusters of aberrant cells that form on the colon’s lining. Although it is not always easy to detect, colon cancer can only be verified by a colonoscopy or surgery. Furthermore, there is now a greater urgency to understand more about how colon cancer operates and how to avoid it due to a recent, as of yet unexplained spike in the disease’s incidence among younger individuals.
It has been a difficult and drawn-out search to determine whether colon cancer is caused by environmental or hereditary factors, but recent research published in Nature suggests a possible lead: a bacteria often found in human mouths. The study discovered a connection between the development and spread of colon cancer and a particular subtype, or clade, within a subspecies of Fusobacterium nucleatum. According to the study’s authors, these findings may pave the way for more effective noninvasive colon cancer detection techniques as well as novel treatments that specifically target these bacteria to eradicate tumors.
F. nucleatum is a naturally occurring microbe in the mouth that is linked to gingivitis and dental plaque. Ten years ago, researchers observed that the bacteria was more frequently present in colon cancer than in healthy colon tissue. According to Susan Bullman, a biologist at the Fred Hutchinson Cancer Center and co-senior author of the current study, “This was particularly interesting because this microbe in noncancerous individuals is usually not present below the [mouth].”
Bullman and her colleagues performed in-depth sequencing on F. nucleatum within colon cancer tumors and examined the microbe’s impact on the intestinal environment to better investigate the microbe’s connection to colon cancer. To compare the genomes of F. nucleatum discovered in colon cancers with those found in the mouth, the scientists first examined the genomes of these malignancies. About 100 persons had their colon tumors taken, which were subsequently broken up and put on agar plates to support the growth of the microorganisms present.
Following the separation of F. nucleatum from these cultures, the researchers used a technique known as long-read sequencing to obtain a thorough understanding of the bacterium’s genome. According to Martha Zepeda-Rivera, the study’s primary author, “assembling a puzzle where you’re not able to get the whole picture” is how most standard sequencing techniques work with what are known as “short reads.” “Long-read sequencing is similar to taking a picture with your camera in which you capture the whole scene.”
The sequences from the colon cancer tissues were compared to those of F. nucleatum from healthy people’s mouths. This identified two primary clades within the subspecies F. nucleatum animals, which were identified by variations in the patterns of encoded proteins and DNA bases. Under a microscope, the two clades of bacteria differed in appearance as well. Specimens from the second clade were longer and thinner than those from the first.
The majority of F. nucleatum animals from the colon tumors belonged to the second clade. The genomes of this clade appeared to code for traits that would aid the bacteria in surviving the treacherous trip from the mouth to the gut, such as the capacity to better infiltrate cells or acquire nutrition in unfavorable settings like an inflamed gastrointestinal tract. According to Christopher Johnston, a geneticist at the Fred Hutchinson Cancer Center and co-senior author of the study, these germs also possess “one of the most potent acid-resistant systems” identified in bacteria, which enables them to withstand the acidic environment of the stomach.
The results indicated that the microorganisms in the second clade were more strongly linked to colon cancer, which prompted the researchers to investigate these microbes’ interactions with the gut in a mouse model in greater detail. After giving a single oral dosage of F. nucleatum animals from haplogroup 1 to one set of mice and a dose of clade 2 to another, the number of tumors that developed was tallied. Comparing mice given clade 2 bacteria to those given clade 1 bacteria or a nonbacterial control, the number of big intestinal tumors produced in the clade 2 group was considerably greater.
When the researchers analyzed the metabolic compounds inside the tumors from the mice carrying the clade 2 bacteria, they discovered that the animals in the control and clade 1 bacteria groups had fewer molecules linked to inflammation, oxidative stress, and cancer cell proliferation. According to Zepeda-Rivera, “This supports the idea that clade 2 bacteria are contributing to this proinflammatory, pro-oncogenic environment.”
According to Harvard Medical School pathologist Shuji Ogino, who was not involved in the current study, finding the F. nucleatum strain associated with colon cancer offers valuable insight into its involvement in disease development. However, he points out that further data from a bigger cohort of colon cancer patients is required, as well as additional investigation to determine the precise role that the bacteria may have in inflammation and the advancement of the disease.
According to Cynthia Sears, a biologist at Johns Hopkins University who peer-reviewed the work, the results of the study may also be useful in the hunt for a low-cost, noninvasive method of identifying individuals who are more likely to develop colon cancer. “We require a strategy that allows us to focus on individuals who pose a greater risk,” she continues. According to Sears, a test that would just check for the presence of these bacteria using a mouth swab or stool sample may be created; clade 2 bacteria were also shown to be more common in fecal samples from those who had colon cancer.
Furthermore, Bullman, Johnston, and Zepeda-Rivera anticipate the development of a vaccine against F. nucleatum animals in clade 2, in addition to diagnostic tools to forecast the progression of cancer. This strategy is comparable to that of the human papillomavirus vaccination, which targets particular viral subtypes that are more frequently associated with illness.
According to the study’s authors, the latest discoveries represent a significant and intriguing advancement in our understanding of how to use these bacteria to combat colon cancer. Given that the particular lineage of cancers has been discovered, Johnston claims that the data “are like a roadmap.” “And with that, we have delineated the distinctions that warrant further investigation.”
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