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Breakthrough Discovery: Oral Microbe’s Role in Colorectal Cancer Unveiled

Visual Representation for Colon Cancer | Credits: iStock

At the Fred Hutchinson Cancer Center, scientists have unearthed a particular strain of microorganism commonly residing in the oral cavity, capable of migrating to the intestinal tract and flourishing within colorectal cancer masses. This microbe not only instigates cancer advancement but also correlates with diminished patient prognoses following cancer therapy.

The revelations, unveiled on March 20 in the pages of the esteemed journal Nature, hold promise for refining therapeutic methodologies and early detection techniques for colorectal cancer, ranking as the second most prevalent cause of adult cancer fatalities in the United States as per the American Cancer Society.

Through scrutiny of colorectal cancer masses extracted from 200 individuals, the team at Fred Hutch assessed the abundance of Fusobacterium nucleatum, a bacterium notorious for infiltrating tumors. Remarkably, nearly half of the cases exhibited heightened levels of a distinct subspecies of the bacterium within the tumor tissue in contrast to healthy tissue.

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Moreover, the scientists observed elevated concentrations of this microorganism in stool samples obtained from colorectal cancer patients compared to those from healthy individuals.

Susan Bullman, Ph.D., a cancer microbiome investigator at Fred Hutch and co-author of the study, elucidated, “Consistently, we’ve observed that patients harboring Fusobacterium nucleatum within colorectal tumors face dismal survival rates and a bleaker prognosis compared to those devoid of this microbe.”

She continued, “Now, our findings underscore the culpability of a specific subtype of this microorganism in tumor proliferation. This implies that therapeutic interventions and screening modalities targeting this subgroup within the microbiome could prove beneficial for individuals predisposed to aggressive colorectal cancer.”

In their investigation, Bullman, along with co-corresponding author Christopher D. Johnston, Ph.D., a molecular microbiologist at Fred Hutch, and the study’s primary author Martha Zepeda-Rivera, Ph.D., a Staff Scientist in the Johnston Lab and a Washington Research Foundation Fellow, sought to unravel the mechanisms by which the microbe traverses from its customary oral habitat to a remote site in the lower intestinal tract and its role in fostering cancer progression.

Their initial revelation unearthed a pivotal finding with potential implications for future therapeutic avenues. Contrary to previous assumptions, the predominant cluster of Fusobacterium nucleatum within colorectal cancer masses, once presumed to be a singular subspecies, is, in fact, comprised of two distinct lineages referred to as “clades.”

Johnston elaborated, “This discovery is akin to stumbling upon the Rosetta Stone in genetic terms. We’ve identified bacterial strains so closely related phylogenetically that we previously regarded them as synonymous, yet we now discern a stark contrast in their prevalence within tumors vis-à-vis the oral cavity.”

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By delineating the genetic disparities between these clades, the researchers uncovered that the tumor-infiltrating Fna C2 variant had acquired unique genetic attributes enabling it to traverse from the oral cavity through the stomach, endure gastric acid, and proliferate in the lower gastrointestinal tract. Genetic analysis revealed 195 divergences between the clades.

Subsequent comparison of tumor tissue and healthy tissue from colorectal cancer patients unveiled that solely the Fna C2 subtype exhibited significant enrichment within colorectal tumor tissue and was accountable for fueling colorectal cancer progression.

Additional molecular fine-tuned evaluation on 200 colorectal tumors through two patient cohorts was done. The results pointed out that almost 50% of the cases were associated with Fna C2 lineage.

In addition, indicating that Fna C2 over-expression was a common phenomenon in colorectal cancer case, we carried out hundreds of stool samples from individuals with colorectal cancer and also without colorectal cancer. And in the result of this study, the featured Fna C2 levels shown consistent correlations with colorectal cancer.

Johnston stated, “Through our research, we have understood the exact bacterial lineage responsible for colorectal cancer, and this knowledge is crucial towards the development of problem-solving prevention and therapeutic measures.”

They and Bullman foresee the field of study they are conducting as a starting point and the doorway to new and unexplored horizons that are concerned with optimizing existing, as well as developing new microbial cellular therapy approaches, introducing genetically modified strains to deliver treatments directly into tumors.

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