Researchers identify gut microbiome signatures linked to precancerous colon polyps

New study looks at gut microbes' influence, findings may help with prevention

A microscope image of human colon cancer cells on a black background. The nuclei of the cells are stained red, and the protein E-cadherin is stained green.
Credit: NCI Center for Cancer Research
Human colon cancer cells.

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A new study by investigators at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard has linked certain types of gut bacteria to the development of precancerous colon polyps. Their results are published in Cell Host & Microbe.

“Researchers have done a lot of work to understand the relationship between the gut microbiome and cancer. But this new study is about understanding the microbiome’s influence on precancerous polyps,” said Daniel Chung, medical co-director of the Center for Cancer Risk Assessment at Mass General Cancer Center, and co-corresponding author on the study with Ramnik Xavier, a core institute member at Broad, co-director of the institute's Infectious Disease and Microbiome Program, and director of the Center for the Study of Inflammatory Bowel Disease at Mass General; and Jonathan Wei Jie Lee, a visiting scientist in the Xavier lab from the National University of Singapore.

“Through the microbiome, we potentially have an opportunity to intervene and prevent colorectal cancer from forming,” Chung said.

Colorectal cancer is the second-leading cause of cancer-related deaths in the US, and rates of colorectal cancer are rising among young adults. Nearly all colorectal cancers arise from a precancerous polyp, the two main types of which are tubular adenomas and sessile serrated polyps. One of the best ways to reduce the incidence of colorectal cancer is to stop the growth at the polyp stage.

There’s more than one way for a polyp to develop. Risk factors for colorectal cancer and polyps include lifestyle factors like being overweight or obese, low physical activity levels, a diet high in red and processed meats, smoking, and alcohol use.

These factors also influence the bacteria that live in our intestines, collectively known as the gut microbiome.

Environmental factors and polyp growth

Researchers think these environmental influences could promote polyp growth in one of two ways. Either they change the gut microbiome directly in a way that encourages polyp growth, or they promote polyp growth, which in turn influences the gut microbiome by directly affecting the cells lining the intestines.

Earlier, smaller studies trying to link the gut microbiome to polyps have not found a consistent pattern, though they didn’t look at these two types of polyps specifically.

To study the gut microbiome’s link to colon polyps, the researchers took data from 1,200 people getting routine screening colonoscopies. They gathered information on their health, diet, medications, and lifestyle, and analyzed stool samples to determine the bacterial makeup of the study group’s gut microbiome.

The new research is the biggest study from an extensive collaborative research program, the GI Disease and Endoscopy Registry at Mass General, which allows these researchers to understand gastrointestinal diseases in greater depth than ever. This registry remains active and ongoing data collection will enable longitudinal follow-up.

The new study, the largest of its kind, analyzed the differences in the gut microbial signature of people without colon polyps, with tubular adenomas, or with sessile serrated adenomas. They also correlated these data with patients’ health and family histories.

Bacterial signatures clustered into three groups based on the type and presence of polyps in the colon. Nineteen bacterial species were significantly different in patients with tubular adenomas than in other populations. In patients with sessile serrated adenomas, eight species were significantly different.

The authors note that the study population was mostly white, limiting generalizability to other population groups, and that the study cannot establish whether bacterial species or adenoma tissue changes first.

The next step is for researchers to isolate specific species of bacteria acting in the gut and see whether they can verify these functional relationships between the bacterial species and polyp growth with a model in a lab.

This information could help develop a probiotic or treatment to lower colorectal cancer risk or as a screening method to assess polyp or colorectal cancer risk.

“The hope is that by changing specific aspects of the diet or the microbiome, we can alter the natural history of these polyps,” Chung said. "Interventions to prevent polyp formation or alter their growth patterns may ultimately prevent colorectal cancer."

Additional authors included Damian Plichta of Broad and Shreya Asher, Marisa Delsignore, Tiffany Jeong, Jessica McGoldrick, Kyle Staller, and Hamed Khalili, of Mass General.

Adapted from a press release issued by Massachusetts General Hospital.


The study was funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of Aging, the Center for Microbiome Informatics and Therapeutics at MIT, and the Center for the Study of Inflammatory Bowel Disease at Mass General.

Paper cited

Lee JWJ, et al. Association of distinct microbial signatures with premalignant colorectal adenomas. Cell Host & Microbe. Online April 30, 2023. DOI: 10.1016/j.chom.2023.04.007.