The Influence of Diet on Cancer Development: Implications for Gastrointestinal Health

MIT researcher Omer Yilmaz’s investigation into the impact of diet on intestinal stem cells reveals its profound effect on overall well-being. His studies indicate that low-calorie diets can have both anti-aging and antitumor properties, while high-fat diets may promote cancer development by increasing the number of stem cells. These findings have significant implications for improving gastrointestinal health and implementing effective cancer prevention strategies.

Yilmaz’s groundbreaking research on the relationship between diet and intestinal stem cells holds promise for developing innovative approaches to treat and prevent gastrointestinal cancers.

The human intestine experiences a complete turnover of cells every three to five days. This constant renewal is crucial for the intestinal lining to withstand the damage caused by food as it passes through the digestive tract.

The maintenance of this rapid cell turnover relies on the presence of intestinal stem cells, which generate all other cell types found in the intestine. Recent investigations demonstrate that these stem cells are highly influenced by diet, which can either support their health or trigger cancerous behavior.

Omer Yilmaz, an associate professor of biology at MIT, explains, “Low-calorie diets like fasting and caloric restriction exhibit antiaging and antitumor effects, and we aim to understand the underlying mechanisms. Conversely, diets that contribute to obesity can foster age-related diseases such as cancer.”

Over the past decade, Yilmaz has dedicated his work to examining how different diets and environmental conditions impact intestinal stem cells, consequently raising the risk of cancer and other diseases. This research could pave the way for the development of novel interventions to enhance gastrointestinal health, either through dietary modifications or the creation of drugs that emulate the positive effects of specific diets.

“Our findings suggest that fasting interventions or the use of small molecules that mimic fasting effects may play a role in enhancing intestinal regeneration,” notes Yilmaz, who is also affiliated with MIT’s Koch Institute for Integrative Cancer Research.

A clinical perspective

Yilmaz’s passion for disease and medicine emerged early in life. With his father practicing internal medicine, Yilmaz spent considerable time at his father’s office and accompanied him during patient visits to hospitals.

“My interest in medicine and how it can be used to treat diseases grew during those experiences,” recalls Yilmaz. “My father would ask me questions, and even if I didn’t know the answers at times, he encouraged me to find them myself. This stimulated my curiosity in biology and fostered my desire to become a doctor.”

Determined to pursue a career in medicine, Yilmaz was accepted into an eight-year combined bachelor’s and MD program at the University of Michigan. This arrangement allowed him the freedom to explore various areas of interest during his undergraduate studies without worrying about medical school applications. He pursued biochemistry and physics, conducting research on protein folding.

Yilmaz’s fascination with disease and medicine, sparked by his father’s influence, continued to grow. (Credit: Jake Belcher)

During his first year of medical school, Yilmaz realized his strong inclination toward research, prompting him to apply to the MD/PhD program at the University of Michigan. For his PhD research, he investigated blood-forming stem cells and identified new markers that facilitated their isolation from the bone marrow.

“This work was significant because it shed light on the characteristics of stem cells, determining the extent to which they are influenced by internal programming versus signals from their microenvironment,” explains Yilmaz.

After completing his MD and PhD degrees, he contemplated diving directly into research and forgoing a medical residency. However, he ultimately chose to complete a residency in pathology at Massachusetts General Hospital. During this period, he made the decision to shift his research focus from blood-forming stem cells to those found in the gastrointestinal tract.

“The gastrointestinal tract fascinated me because, unlike the bone marrow, little was known about the identity of gastrointestinal stem cells,” says Yilmaz. “I knew that identifying these stem cells would raise compelling questions about their response to diet and other environmental factors.”

Exploring dietary impact

To delve into these questions, Yilmaz embarked on postdoctoral research at the Whitehead Institute, where he started investigating the connections between stem cells, metabolism, diet, and cancer.

As intestinal stem cells have long lifespans, they are more susceptible to accumulating genetic mutations that make them prone to becoming cancerous. At the Whitehead Institute, Yilmaz began investigating how various diets might influence this vulnerability to cancer, an area he continued to explore when he joined MIT’s faculty in 2014.

One key question his laboratory has pursued is why low-calorie diets consistently exhibit protective effects, including enhanced longevity—an effect observed in numerous studies involving animals and humans.

In a 2018 study, Yilmaz’s team discovered that a 24-hour fast significantly enhances the regenerative capacity of stem cells. This effect was observed in both young and aged mice, indicating that fasting or drugs that mimic fasting effects could be beneficial even in old age.

Conversely, Yilmaz also investigates why high-fat diets seem to promote cancer development, particularly colorectal cancer. In a 2016 study, he demonstrated that a high-fat diet triggers a significant increase in the number of intestinal stem cells. Furthermore, certain non-stem-cell populations exhibit stem cell-like behavior. “These changes result in both stem cells and non-stem cells giving rise to tumors under high-fat diet conditions,” explains Yilmaz.

To support these studies, Yilmaz’s laboratory has developed a method to generate miniature intestines or colons using mouse or human intestinal stem cells in cell culture. These “organoids” can be exposed to different nutrients in a highly controlled setting, enabling researchers to analyze how various diets affect the system.

Recently, his team expanded this approach to include immune cells, fibroblasts, and other supportive cells found in the stem cell microenvironment. “It is important for us to consider multiple cell types,” emphasizes Yilmaz. “We are examining how different dietary interventions impact the entire stem cell community.”

While Yilmaz primarily dedicates his time to running his laboratory at MIT, he also spends six to eight weeks each year working at Massachusetts General Hospital, where he serves as an associate pathologist specializing in gastrointestinal pathology.

“I derive great satisfaction from my clinical work, as it continually reminds me of the importance of our research,” he shares. “Observing colon cancer and other gastrointestinal cancers under the microscope, witnessing their complexity, serves as a reminder of our mission to prevent the formation of these cancers.”

Frequently Asked Questions (FAQs) about dietary impact

More about dietary impact

• MIT News: Diet & Destiny: How Your Food Choices Influence Cancer Development
• MIT Koch Institute: Omer Yilmaz Lab
• ScienceDaily: Low-calorie diet promotes intestinal regeneration after injury in mice
• Nature: A high-fat diet induces stemness features in normal mouse intestinal stem cells