The type of diet directly influences our health and abusing certain foods contributes to the appearance of diseases such as obesity or diabetes, but knowing the specific causes why certain products are harmful can be of great help when designing diets. to prevent health problems. Now, a new study has found the reasons why high-fat diets increase the risk of developing colorectal cancer.
The research has been carried out by scientists from the Salk Institute and the University of California at San Diego, who have carried out their experiments on mice. These researchers have found that fats alter gut bacteria and, in particular, have identified specific microbes and bile acids that become more abundant in the intestines of mice fed high-fat diets. Bile acids are molecules produced by the liver that are used by the intestine to help digest food and absorb cholesterol, fats, and nutrients.
It was already suspected that the increased prevalence of colorectal cancer in those under 50 years of age was associated with rising rates of obesity and high-fat diets. The authors of the new work found high levels of specific intestinal bacteria in rodents fed a high-fat diet, and that these bacteria modified the composition of the bile acid pool in a way that caused inflammation and influenced the speed with which intestinal stem cells are replenished.
“We have deconstructed why high-fat diets are not good for you and identified specific strains of microbes that are exacerbated by high-fat diets.”
“The balance of microbes in the gut is determined by diet and we are discovering how alterations in the gut microbial population (the gut microbiome) can create problems that lead to cancer,” said co-senior author Professor Ronald Evans, Director from the Salk Gene Expression Laboratory. “This paves the way for interventions that reduce the risk of cancer.” His findings have been published in Cell Reports.
The impact of a high-fat diet on the gut microbiome
In 2019, Evans and colleagues demonstrated in mice how high-fat diets increased overall bile acid levels. They found that the change in bile acids turned off a key protein in the intestine, called the farnesoid X receptor (FXR), and increased the prevalence of cancer. However, data was still lacking, including how high-fat diets modify the gut microbiome and bile acids.
In the new study, they analyzed the microbiomes and metabolomes (collections of microbe-derived and dietary small molecules) in the digestive tracts of animals on high-fat diets, and studied mice with a genetic mutation that makes them more susceptible to colorectal tumors.
They found that although mice fed high-fat diets had more bile acids in their gut, they were a less diverse group with a higher prevalence of certain bile acids that had been modified by gut bacteria. They also showed that these modified bile acids influenced the proliferation of stem cells in the intestines. When these cells are not replaced frequently, they can accumulate mutations, a key process in promoting the growth of cancers, which often arise from these stem cells.
They also found relevant differences in the microbiomes of mice on high-fat diets: collections of gut bacteria in the digestive tracts of these animals were less diverse and contained different bacteria than the microbiomes of mice not fed high-fat diets. in fats. Two of these bacteria – Ileibacterium valens and Ruminococcus gnavus – were capable of producing these modified bile acids.
The researchers were surprised to find that a high-fat diet actually had a greater impact on the microbiome and modified bile acids more than a genetic mutation that increases cancer susceptibility in animals. “We have identified how a high-fat diet influences the gut microbiome and reshapes the bile acid reserve, pushing the gut into an inflamed and disease-associated state,” says co-author Ting Fu, a former postdoctoral fellow in the Evans lab.
In the opinion of these scientists, diets high in fat modify the composition of the microbiome, favoring the growth of bacteria such as I. valens and R. gnavus. In turn, this increases the levels of modified bile acids, and in a vicious cycle, these bile acids create a more inflammatory environment that can further change the composition of gut bacteria.
“We have deconstructed why high-fat diets are not good for your health and identified specific strains of microbes that are exacerbated by high-fat diets,” says Evans, chair of Molecular and Developmental Biology at the March of Dimes. “By knowing what the problem is, we have a much better idea of how to prevent and reverse it.”
