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<td><a href="https://directorsblog.nih.gov/2024/04/11/microbe-normally-found-in-the-mouth-may-drive-progression-of-colorectal-cancer/" style="font-family:Helvetica, sans-serif; letter-spacing:-1px;margin:0;padding:0 0 2px;font-weight: bold;font-size: 19px;line-height: 20px;color:#222;">Microbe Normally Found in the Mouth May Drive Progression of Colorectal Cancer</a>
<div style="font-family:Helvetica, sans-serif; text-align:left;color:#999;font-size:11px;font-weight:bold;line-height:15px;">Apr 11th 2024, 09:11</div>
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<figure class="wp-block-image size-large"><img fetchpriority="high" decoding="async" width="1024" height="576" src="https://directorsblog.nih.gov/wp-content/uploads/2024/04/Microbe-colorectal-cancer-1024x576.jpg" alt="Microscopy of Fusobactium nucleatum coming from the GI tract" class="wp-image-25786" srcset="https://directorsblog.nih.gov/wp-content/uploads/2024/04/Microbe-colorectal-cancer-1024x576.jpg 1024w, https://directorsblog.nih.gov/wp-content/uploads/2024/04/Microbe-colorectal-cancer-300x169.jpg 300w, https://directorsblog.nih.gov/wp-content/uploads/2024/04/Microbe-colorectal-cancer-150x84.jpg 150w, https://directorsblog.nih.gov/wp-content/uploads/2024/04/Microbe-colorectal-cancer-768x432.jpg 768w, https://directorsblog.nih.gov/wp-content/uploads/2024/04/Microbe-colorectal-cancer-1536x864.jpg 1536w, https://directorsblog.nih.gov/wp-content/uploads/2024/04/Microbe-colorectal-cancer-180x100.jpg?crop=1 180w, https://directorsblog.nih.gov/wp-content/uploads/2024/04/Microbe-colorectal-cancer.jpg 1920w" sizes="(max-width: 1024px) 100vw, 1024px"><figcaption class="wp-element-caption"><em>Study findings suggest a subtype of Fusobacterium nucleatum, a microbe normally found in the mouth, may infect colorectal tumors and drive their growth. Credit: Donny Bliss/NIH</em>,<em> Appledesign/Adobe stock</em></figcaption></figure><p>Colorectal cancer is <a href="https://www.cdc.gov/cancer/colorectal/basic_info/" target="_blank" rel="noreferrer noopener">a leading cause of death</a> from cancer in the United States. We know that <a href="https://www.cancer.gov/types/colorectal/patient/colorectal-prevention-pdq#_14" target="_blank" rel="noreferrer noopener">risk of colorectal cancer</a> goes up with age, certain coexisting health conditions, family history, smoking, alcohol use, and other factors. Researchers are also trying to learn more about what leads colorectal cancer to grow and spread. Now, findings from a new study supported in part by NIH add to evidence that colorectal tumor growth may be driven by a surprising bad actor: a microbe that’s normally found in the mouth.<sup>1</sup></p>
<p>The findings, reported in <a href="https://pubmed.ncbi.nlm.nih.gov/38509359/" target="_blank" rel="noreferrer noopener"><em>Nature</em></a>, suggest that a subtype of the bacterium <em>Fusobacterium nucleatum</em> has distinct genetic properties that may allow it to withstand acidic conditions in the stomach, infect colorectal tumors, and potentially drive their growth, which may lead to poorer patient outcomes. The discoveries suggest that the microbe could eventually be used as a target for detecting and treating colorectal cancer.</p>
<p>The study was conducted by a team led by <a href="https://www.fredhutch.org/en/faculty-lab-directory/bullman-susan.html" target="_blank" rel="noreferrer noopener">Susan Bullman</a> and <a href="https://www.fredhutch.org/en/faculty-lab-directory/johnston-christopher.html">Christopher D. Johnston</a> at the Fred Hutchinson Cancer Center in Seattle. In 2022, the team published findings from a pair of studies implicating <em>Fusobacterium nucleatum</em> in the progression and spread of colorectal cancer.<sup>2,3</sup> Their findings weren’t the first to suggest a link between the microbe and colorectal cancer. But their work offered important evidence that the microbe might alter colorectal tumors in ways that made them more likely to grow and spread. They also found that the microbe may affect the way colorectal cancer responds to or resists chemotherapy treatment.</p>
<p>Follow-up studies suggested there might be more to the story, pointing to the possibility that certain strains of the bacterium might differ from others in important ways. The findings suggested that there may be a more specific subtype<em>, </em>not yet defined, that was responsible for driving colorectal cancer growth.</p>
<p>To look deeper into this in the new study, Bullman and Johnston, with first author <a href="https://www.fredhutch.org/en/research/divisions/vaccine-infectious-disease-division/faculty-labs/vidd-staff-scientists-physicians/zepeda-rivera-martha.html" target="_blank" rel="noreferrer noopener">Martha Zepeda Rivera</a>, analyzed a collection of 55 strains of the microbe taken from human colorectal cancer samples. They also compared these at the genetic level to another 80 strains of the microbe taken from the mouths of people who didn’t have cancer.</p>
<p>Their studies uncovered 483 genetic factors that turned up more often in <em>Fusobacterium nucleatum </em>from colorectal tumors. Those strains mainly belonged to a subspecies called <em>Fusobacterium nucleatum animalis </em>(<em>Fna</em>). More detailed study led to another surprise. The <em>Fna </em>included two genetically distinct groups or “clades” that had never been described, which the researchers called <em>Fna</em> C1 and C2. It turned out that only <em>Fna </em>C2 occurs at high levels in colorectal tumors.</p>
<p>The researchers found that this specific subtype within colorectal tumors carries 195 genetic factors that may allow it to grow more rapidly, withstand the acidic environment in the stomach, and take up residence in the gastrointestinal tract, where it can drive colorectal cancer growth. When the researchers infected a mouse model of colitis, a condition involving inflamed intestines that is a risk factor for colorectal cancer, they found that <em>Fna</em> C2 caused the development of more tumors compared to those infected with <em>Fna </em>C1.</p>
<p>Studies of tumors from 116 patients with colorectal cancer also showed more <em>Fna </em>C2. It was elevated in about 50% of cases. In fact, only this strain turned up more often in cancer compared to healthy tissue nearby. Stool samples of 627 people with colorectal cancer and 619 healthy people also showed more of this specific microbial strain in association with cancer.</p>
<p>This discovery is important because it suggests it’s only the <em>Fna</em> C2 subtype that’s associated with driving colorectal tumor growth, meaning it could help in the development of new methods for colorectal cancer screening and treatment. The researchers suggest it may one day even be possible to develop microbial-based therapies using modified versions of the bacterial strain to deliver treatments straight into tumors.</p>
<p>In addition, while the microbe is normally found in healthy mouths, it’s also enriched in periodontal (gum) disease, dental infections, and oral cancers.<sup>4</sup> It will be interesting to learn more in future studies about the connections between various <em>Fusobacterium nucleatum </em>subtypes<em>, </em>oral health, and other health conditions throughout the body, including colorectal cancer. </p>
<p><strong>References:</strong></p>
<p>[1] Zepeda-Rivera M, <em>et al</em>. <a href="https://pubmed.ncbi.nlm.nih.gov/38509359/" target="_blank" rel="noreferrer noopener">A distinct Fusobacterium nucleatum clade dominates the colorectal cancer niche</a>. <em>Nature</em>. DOI: 10.1038/s41586-024-07182-w (2024).</p>
<p>[2] LaCourse KD, <em>et al</em>. <a href="https://pubmed.ncbi.nlm.nih.gov/36384132/" target="_blank" rel="noreferrer noopener">The cancer chemotherapeutic 5-fluorouracil is a potent Fusobacterium nucleatum inhibitor and its activity is modified by intratumoral microbiota</a>. <em>Cell Rep</em>. DOI: 10.1016/j.celrep.2022.111625 (2022).</p>
<p>[3] Galeano Niño JL, <em>et al</em>. <a href="https://pubmed.ncbi.nlm.nih.gov/36385528/" target="_blank" rel="noreferrer noopener">Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer</a>. <em>Nature</em>. DOI: 10.1038/s41586-022-05435-0 (2022).</p>
<p>[4] Chen Y, <em>et al</em>. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851061/" target="_blank" rel="noreferrer noopener">More Than Just a Periodontal Pathogen –the Research Progress on <em>Fusobacterium nucleatum</em></a>. <em>Front Cell Infect Microbiol</em>. DOI: 10.3389/fcimb.2022.815318 (2022).</p>
<p><em>NIH Support: National Institute of Dental and Craniofacial Research, National Cancer Institute</em></p>
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<p><strong>Forwarded by:<br />
Michael Reeder LCPC<br />
Baltimore, MD</strong></p>
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