Persistent gut microbiome changes linked to sustained colorectal cancer risk

More than a decade after removal of an adenoma-a precancerous mass-from the colon, alterations to the gut microbiome and metabolites remain and may drive heightened risk of colorectal cancer (CRC), according to a new study led by researchers at Harvard T.H. Chan School of Public Health. The study also found that diet and physical activity were more closely tied to the abundance of these CRC-associated gut microbes in people with a history of adenoma than in adenoma-free individuals, suggesting lifestyle may play a particularly important role in shaping these microbes in this high-risk group.

CRC is the second leading cause of cancer-related death worldwide, and adenoma removal is one of the most effective prevention tools. Yet people who've had this procedure still face an elevated risk of CRC. The biological reasons why have remained unclear, but the gut microbiome-the collection of trillions of bacteria living in the gastrointestinal tract-is a plausible suspect.

Our study was the first to address whether gut microbial and metabolic alterations are still detectable many years after adenoma removal. The answer is yes-suggesting that removing an adenoma doesn't return the gut to a low-risk state, and that the gut microbiome may therefore be a significant biological contributor to sustained CRC risk."

Mingyang Song, corresponding author, associate professor of clinical epidemiology and nutrition

The study will be published May 27 in Cell Host & Microbe.

Previous research linking the gut microbiome to CRC risk examined patients' gut microbiomes only around the time of adenoma removal. For this study, the researchers took a long-term approach using health data and stool samples from women enrolled in the Nurses' Health Study II. They studied the microbiomes of 354 participants who had an adenoma removed from their colon and compared them to the microbiomes of 354 adenoma-free participants closely matched in age and background. Stool samples were collected on average 12 years after adenoma removal.

The study found that significant differences persisted between the gut microbiomes and metabolites of adenoma-free participants and those who'd had an adenoma, even more than a decade after removal. The latter group had microbiomes that partially resembled those belonging to CRC patients. Among participants with a history of adenoma, those with less healthy diets and lower physical activity carried more of the microbes that are typically elevated in both adenoma and CRC patients. These links between lifestyle and microbes were tighter in participants with a history of adenoma than in adenoma-free participants.

"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," said first author Ana Nogal, postdoctoral research fellow in the Department of 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 researchers noted that the study shows association rather than causation, and that future research is needed to directly test whether modifying the gut microbiome through diet and exercise habits does successfully alter CRC risk.