More than a decade after surgery to remove a precancerous mass from the colon, the gut microbiome still bears the scars—and may continue to fuel colorectal cancer risk, according to research from Harvard T.H. Chan School of Public Health published in Cell Host & Microbe.
The discovery matters because colorectal cancer is the second leading cause of cancer-related death worldwide, and adenoma removal—one of the most effective prevention strategies—still leaves patients vulnerable. Now researchers led by associate professor Mingyang Song have found a likely culprit: the gut's bacterial ecosystem doesn't actually return to a healthy state after the procedure.
The Harvard team examined health data and stool samples from 354 women in the Nurses' Health Study II who had undergone adenoma removal, comparing them to 354 adenoma-free participants matched by age and background. The samples were collected an average of 12 years after surgery. The results were striking. Significant differences persisted between the two groups' gut microbiomes and metabolites—the compounds produced by bacteria. The adenoma survivors' microbiomes partially resembled those of colorectal cancer patients themselves, suggesting a lingering biological vulnerability.
What made the findings especially relevant to people's daily lives was the role of lifestyle. Among participants with adenoma history, those who maintained less healthy diets and lower physical activity levels carried higher abundances of microbes typically elevated in both adenoma and cancer patients. These connections between habits and microbial composition were considerably tighter in the adenoma group than in adenoma-free participants, suggesting that diet and exercise may be particularly powerful levers for this high-risk population.
"The fact that CRC-associated gut microbial and metabolic features are still detectable a decade later suggests the gut microbiome may be part of sustained CRC risk," explained Ana Nogal, the study's first author and a postdoctoral research fellow in epidemiology. "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."
The research marks the first time scientists have tracked whether these microbial and metabolic changes persist years after adenoma removal—previous studies had only examined patients around the time of surgery. That long view proved crucial. It revealed that adenoma removal alone doesn't restore the gut to a low-risk state, which explains why patients remain at elevated risk even after what is often considered a successful intervention.
The findings open a path forward, though researchers emphasize that the study shows association, not causation. Future work must test whether deliberately modifying the gut microbiome through diet and exercise actually reduces colorectal cancer risk in this population. For now, the message is clear: surviving adenoma removal is not the end of the cancer prevention story. The gut remembers, and lifestyle choices—what we eat and how active we are—may play an outsized role in determining whether that memory becomes a problem.