How high-fat diets may increase the risk

In their study, researchers at the Salk Institute and the University of California San Diego fed lab mice with a genetic predisposition to colorectal cancer a high fat diet.

They tracked changes in their gut bacteria and altered digestive molecules called bile acids, which are produced by the liver and help digest food and absorb cholesterol, fats, and nutrients.

The study authors reported that a fatty diet increased the levels of certain gut bacteria that, in turn, altered bile acids in a way that increased inflammation and inhibited the replenishment of intestinal stem cells, which help to repair cellular damage in the body.

Those changes can raise the risk of colorectal cancer, according to Ronald Evans, PhD, a senior study author and the director of Salk’s Gene Expression Laboratory, and his colleagues.

“We’ve deconstructed why high fat diets aren’t good for you and identified specific strains of microbes that flare with high fat diets,” Dr. Evans said in a press statement. “By knowing what the problem is, we have a much better idea of how to prevent and reverse it.”

In a 2019 study, a research group led by Evans reported that an increase in bile acids shut down a protein in the gut called the farnesoid X receptor (FXR), which is involved in lipid and energy metabolism and reducing inflammation.

The new study shows that the changes in bile acids also affected the proliferation of stem cells in the intestines.

The paper noted that stem cells that replenish more slowly may mutate and encourage the growth of colorectal cancers, which often arise from stem cells.

Two types of gut bacteria shown to affect bile acids, Ileibacterium valens and Ruminococcus gnavus, were much more prevalent in the guts of mice on high fat diets, according to the study findings.

A high-fat diet seemed to have a more profound effect on the gut microbiome and bile acids than the genetic mutation that made the mice more susceptible to colorectal cancer, the researchers said.

“We’ve known that a high fat diet, along with a diet high in red meat, tends to increase the risk of colon polyp formation and colon cancer,” Dr. Jesse P. Houghton, a senior medical director of gastroenterology at the Southern Ohio Medical Center, told MNT.

“This new research links the high fat diet with a detrimental change in the composition of the gut microbiome, leading to an increase in inflammatory bile acids, which in turn leads to a downregulation in the FXR receptor. This research elegantly connects the dots in previously known risk factors for colorectal cancer, providing a road map detailing how we go from macronutrients to molecular changes.”

— Dr. Jesse P. Houghton, gastroenterologist

Evans and colleagues suggested that the FXR receptor could be targeted for future interventions to prevent colorectal cancer.

Bilchik said that while human clinical studies are still needed to confirm the study findings and possibly develop new treatments, “up to 70% of colorectal cancer is preventable through a healthy lifestyle, exercise, and a balanced diet.”

Meanwhile, another study recently published in JAMA Network Open suggested that taking vitamin D supplements could help reduce the risk of relapse or death in a specific subset of digestive cancers, including colorectal cancer.

“Being at a normal weight and taking vitamin D improves your ability to survive cancer. Other factors include the patient’s genetic makeup and how the patient utilizes and breaks down vitamin D,” said Dr. Michael F. Holick, a professor of medicine, pharmacology, physiology and biophysics as well as a molecular medicine at Boston University’s Chobanian & Avedisian School of Medicine, in a related commentary.