High-sugar and high-fat diets significantly increase the risk of colorectal cancer

2023-12-02

Colorectal cancer is the most common type of cancer in terms of incidence and death worldwide, and the incidence rate of colorectal cancer has continued to increase in recent years. Scientists have found that diet and lifestyle are significantly related to colorectal cancer. In particular, the intake of high-sugar and high-fat diets will affect the survival pattern of the intestinal microbiome, laying hidden dangers for the occurrence of colorectal cancer.

Recently, scientists from the Salk Institute and the University of California, San Diego, collaborated to confirm that mice that eat a high-fat diet for a long time have an increase in the number of specific microorganisms in the intestines and changes in bile acid metabolism in the intestines. These all make the mice more susceptible to colorectal cancer.

Bile acids include a series of cholesterol derivatives, including cholic acid synthesized by hepatocytes, chenodeoxycholic acid, and bile acid products modified by microbial metabolism, which can promote intestinal lipid absorption. A high-fat diet changes this process and makes the intestinal microenvironment more pro-inflammatory and pro-cancer.

Professor Ronald Evans, the lead author of the study, discovered a few years ago that a high-fat diet can increase the overall level of bile acids in mice, and that the increase in bile acids inhibits the FXR protein in the intestine, which happens to regulate and transport bile. The key to acidity. This suggested to them that a high-fat diet made the intestines different from before, but what details remained undiscovered? This time, they decided to go back to mice with colorectal cancer to search for clues.

The research team created genetically mutated mice that would make them genetically more susceptible to colorectal cancer. With the support of a high-fat diet, the researchers again observed that the bile acid levels in the intestines of mice increased a lot, but this time they found subtle changes, that is, the diversity of bile acid composition decreased. The proportion of bile acids modified by intestinal microorganisms has increased significantly.

Correspondingly, the diversity of microorganisms in the intestines of mice on a high-fat diet is also changing quietly. Compared with the control group, the diversity of intestinal microorganisms in mice on a high-fat diet has decreased, while Ileibacterium valens and Ruminococcus produce modified bile acids. The number of gnavus increased instead.

These modified bile acids accumulate in large amounts in the intestine, affecting the proliferation of intestinal stem cells and continuing to increase inflammation levels. The authors note that when these stem cells no longer renew themselves frequently, they tend to accumulate mutations that make cancer more likely to develop. Research confirms that high-fat diets have negative effects on gut microbes and bile acids even more than at the genetic level. These changes shift the gut toward inflammatory and cancer-related states.

In fact, these changes start an automatic cycle, as inflammation further alters the gut microbiome.

In the future, Professor Evans plans to further learn from existing findings to find ways to prevent or even reverse the occurrence of colorectal cancer, such as reducing the number of Ileibacterium valens and reducing the levels of specific modified bile acids. However, the best way is still to start with prevention and reduce the frequency of high-fat diet intake in life.