Lasting Gut Microbiome Changes May Keep Colorectal Cancer Risk Elevated After Precancerous Polyps

Researchers found that people with a history of these polyps, called adenomas, still had differences in their gut bacteria and stool chemicals years later that resembled patterns seen in people with colorectal cancer. Among adults who had adenomas removed, these microbiome changes were more pronounced for those who got less physical activity and had less healthy eating habits.

Research had previously shown that people who have adenomas removed remain at higher risk for colorectal cancer — but it hasn’t been clear why, says study coauthor Ana Nogal, PhD, a postdoctoral research fellow in epidemiology at Harvard T.H. Chan School of Public Health in Boston.

“Our findings point to the gut microbiome as one plausible contributor,” says Dr. Nogal.

This is the first study to show a “potential continuum of change in the gut microbiome that links adenomas and colon cancer,” says Cynthia Sears, MD, a professor of medicine and oncology and microbiome program leader at Johns Hopkins University School of Medicine in Baltimore, who was not involved in the study.

Diet and Lifestyle Habits Matter for People With a History of Colon Polyps

Researchers analyzed the microbiomes of more than 350 adults who’d had an adenoma removed from their colon. They compared these microbiomes to those of about 350 adenoma-free participants closely matched in age and background. Participants provided stool samples about 12 years later, on average.

Researchers compared these microbiome results with patterns tied to colorectal cancer from earlier studies. This data set included more than 2,100 stool samples from people with and without colorectal cancer.

Key findings included:

• People with a history of adenomas still had different gut bacteria and stool metabolites compared with people who’d never had polyps, even more than a decade later.
• Some of those gut microbiome patterns partly resembled patterns seen in people with colorectal cancer.
• Among people with a history of adenomas, those who got less exercise and had less healthy diets (higher in sugary drinks and lower in whole grains, fruits, and vegetables) had more of the microbes typically elevated for people with both adenomas and colorectal cancer.
• The link between lifestyle and these cancer-associated microbes was stronger in people with a history of adenomas than in people who had never had polyps.

“Diet and lifestyle were closely tied to these microbes, raising the possibility that these habits could influence the gut environment in people at higher risk,” says Nogal.

That message fits with what researchers already know about colorectal cancer prevention: Diet is critical. That means “less red meat, more vegetables and fruits, exercise, and weight management,” says Dr. Sears.

Strengths and Limitations of the Findings

The strength of this study is that it used data from the Nurses’ Health Study 2, a large, long-running cohort with detailed lifestyle information, says Sears.

It suggests there’s a lasting link between the microbiome and the risk for polyps and colon cancer. Still, the findings cannot prove that microbiome changes cause colorectal cancer.

Limitations include the fact that only women were studied, stool was collected only once, and the researchers did not have stool samples from the time of colonoscopy or long-term outcomes showing who later developed more polyps or cancer.

The gut microbiome differences were also subtle, Sears says. That means the study helps scientists understand risk biology, but “it does not provide a roadmap to new diagnostics or an enhanced ability to pluck out of a crowd the person at risk,” says Sears.

“Our study doesn’t directly address rising rates, but it contributes one piece,” says Nogal. Whether the same microbiome features are relevant in younger adults “will need to be tested directly,” she adds.

Steps to Lower Colorectal Cancer Risk

The new study is a good reminder that people who have adenomas removed should continue to get screened for colon cancer, says Sears.

For these adults — especially if they had larger or more concerning adenomas — their doctor would usually recommend coming back for another colonoscopy sooner than someone without polyps, she adds.

• Don’t smoke or use tobacco products.
• Avoid alcohol or drink only in moderation.
• Stay physically active.
• Maintain a weight that’s healthy for you.
• Limit red meat or processed meat in your diet.