‘Unique opportunity’ in study of colorectal cancer

Growing scientific evidence points to a potential role for specific oral microorganisms in the development and progression of colorectal cancer, yet relatively few studies have been able to examine oral, stool, and tumor samples collected from the same patients.

Now, researchers at Harvard School of Dental Medicine (HSDM) will have an opportunity to investigate how microorganisms originating in the mouth may interact with the gut and contribute to disease through a statewide biobank initiative supported by the Massachusetts Life Sciences Center.

The center is funding 13 projects at 11 academic medical centers and research institutions, to expand access to patient biospecimens and associated clinical data.

HSDM is among institutions participating in the colorectal cancer effort, providing researchers in the Feres Lab with access to a resource that could help answer questions that have been difficult to study using conventional datasets.

“This gives us a unique opportunity to advance our understanding of the oral-gut microbiome axis in colorectal cancer,” said Magda Feres, professor and chair of Oral Medicine, Infection & Immunity, who leads the Feres Lab at HSDM. “By integrating oral, stool, and tumor samples from the same patients with state-of-the-art multi-omics analyses and machine learning, we can move closer to breakthroughs in early diagnosis and prevention. We are thrilled to be part of this initiative.”

The project builds on a growing area of research examining connections between the oral microbiome — the community of microorganisms that inhabit the mouth — and diseases elsewhere in the body. Certain oral bacteria have been detected in colorectal tumors, raising questions about whether changes in the oral microbiome or the migration of specific microorganisms from the mouth to the gastrointestinal tract could contribute to the development or progression of CRC.

Determining the significance of those associations, however, requires researchers to look across different biological environments within the same individual. By analyzing matched oral, stool, and tumor specimens, the HSDM team will be able to investigate microbial and molecular patterns across the mouth, gut, and tumor rather than studying each site in isolation.

The researchers plan to apply multi-omics approaches to characterize the biological information contained in the samples and use machine learning to identify combinations of microbial and molecular features associated with colorectal cancer. Ultimately, those analyses could help researchers identify biomarkers that distinguish patients with colorectal cancer or potentially signal disease at an earlier stage.

“The rich data that can be collected here, combined with state-of-the-art methods to study the oral-gut microbiome and novel machine-learning predictive models, represent one of the best opportunities to date to identify microbial signatures associated with colorectal cancer and potentially inform future prevention strategies,”Feres said.

One long-term possibility is particularly compelling: translating discoveries from the microbiome into a simple, noninvasive screening tool.

“If we can identify a microbial or molecular signature that reliably tracks with colorectal cancer, it is not difficult to imagine that signature being detected in saliva or stool,” said Eduardo de Souza Oliveira, lecturer and researcher in the Feres Lab. “That would not replace existing screening methods such as colonoscopy. But it could help identify who most needs one, and it could reach people who are not being screened at all today.”

Feres sees a precedent in Helicobacter pylori. “H. pylori transformed our understanding of peptic ulcer disease and is now recognized as a major risk factor for gastric cancer,” she said. “But for decades, nobody was looking for it. We don’t yet know whether there are microorganisms playing similar roles in colorectal cancer, but that is exactly why we need to look.”

While considerable research would be needed before a comparable approach could be developed for colorectal cancer, the biobank creates an important foundation for pursuing that possibility.

The HSDM project is part of a broader Massachusetts effort to build shared research infrastructure around high-quality patient samples and linked clinical data. The statewide initiative brings together academic medical centers and research institutions with industry partners providing expertise in areas including regulatory oversight, secure data systems, privacy-preserving data linkage and biospecimen management.

For the Feres Lab, that collaborative infrastructure offers something particularly valuable: the ability to connect oral health research with cancer biology at a scale that would be difficult for an individual laboratory to achieve alone.

“This is the type of research that becomes possible when we break down traditional boundaries between fields,” Feres said. “By bringing oral microbiology, cancer research, multi-omics, and data science together, we have an opportunity to better understand colorectal cancer — and potentially identify new ways to detect it before it progresses.”