International Business Department           Liu Bojia           August 28, 2023

  Colorectal cancer is one of the most prevalent types of cancer worldwide in terms of morbidity and mortality, and the incidence of colorectal cancer has continued to rise in recent years. Scientists have found that diet and lifestyle are significantly associated with colorectal cancer, especially the intake of high-sugar and high-fat diets, which affect the survival mode of the gut microbiome and pose a risk for the development of colorectal cancer.

  Recently, scientists from the Salk Institute for Biological Studies (Salk Institute) and the University of California, San Diego, collaborated to show that mice consuming a high-fat diet for a prolonged period of time have increased populations of specific microorganisms in the gut and altered metabolism of bile acids in the gut, which can make them more susceptible to colorectal cancer.

  Bile acids comprise a range of cholesterol derivatives, including bile acids synthesized by hepatocytes, goose deoxycholic acid, and also microbial metabolism of modified bile acid products, which promote intestinal absorption of lipids. It is this process that is altered by a high-fat diet and makes the intestinal microenvironment more pro-inflammatory and pro-cancer.

  The lead author of the study, Prof. Ronald Evans, discovered several years ago that a high-fat diet elevated overall levels of bile acids in mice, and that the increase in bile acids inhibited FXR proteins in the gut, which happen to be key in regulating and transporting bile acids. This hinted to them that the high-fat diet was making the gut a different place than it used to be, but what other details were missing? This time, they decided to go back to searching for clues in colorectal cancer mice.

  The team constructed mice with a genetic mutation that would make them genetically more susceptible to colorectal cancer. With the addition of a high-fat diet, the researchers once again observed much higher levels of bile acids in the mice's intestines, but this time they found the subtle change, which was a decrease in the diversity of bile acid compositions, with a substantial increase in the percentage of bile acids that were modified by gut microbes.

  In contrast, the microbial diversity in the gut of mice on a high-fat diet also changed, with a decrease in the diversity of gut microorganisms and an increase in the number of Ileibacterium valens and Ruminococcus gnavus, which produce modified bile acids, in mice on a high-fat diet compared with the control group.

  Massive accumulation of these modified bile acids in the gut affects the proliferation of intestinal stem cells and consistently increases levels of inflammation. The authors noted that when these stem cells are no longer frequently renewed, they become prone to accumulating mutations thus making cancer more likely. The study confirms that the negative effects of a high-fat diet on gut microbes and bile acids are even greater than those at the genetic level, and that these changes shift the gut towards an inflammatory and cancer-related state.

  In fact, these aforementioned changes actually act like they start a cycle that works on its own, as inflammation further alters the gut microbiome.

  In the future, Prof. Evans further plans to find ways to stop or even reverse the development of colorectal cancer from what has already been discovered, such as reducing the number of Ileibacterium valens and lowering the levels of specific modified bile acids. However, the best approach is still to start with prevention by reducing the frequency of high-fat diets in your life.