The intestine is essential for maintaining energy balance and is a master at reacting quickly to changes in nutrition and nutrient balance. It manages to do this with the help of intestinal cells that among other things are specialized in the absorption of food components or the secretion of hormones.
In adult humans, the intestinal cells regenerate every five to seven days. The ability to constantly renew and develop all types of intestinal cells from intestinal stem cells is crucial for the natural adaptability of the digestive system. However, a long-term diet high in sugar and fat disrupts this adaptation and can contribute to the development of obesity, type 2 diabetes, and gastrointestinal cancer. The findings have been published in Nature Metabolism.
The molecular mechanisms behind this maladaptation are part of the research field of Heiko Lickert and his group at Helmholtz Munich and the Technical University of Munich. Scientists assume that intestinal stem cells play a special role in maladaptation. Using a mouse model, the researchers investigated the effects of a high-sugar and high-fat diet and compared it with a control group.
From high-calorie diet to increased risk of gastrointestinal cancer
“The first thing we noticed was that the small intestine increases greatly in size on the high-calorie diet,” says study leader Anika Bottcher. “Together with Fabian Theis’ team of computational biologists at Helmholtz Munich, we then profiled 27,000 intestinal cells from control diet and high fat/high sugar diet-fed mice. Using new machine learning techniques, we thus found that intestinal stem cells divide and differentiate significantly faster in the mice on an unhealthy diet.” The researchers hypothesize that this is due to an upregulation of the relevant signalling pathways, which is associated with an acceleration of tumour growth in many cancers. “This could be an important link: Diet influences metabolic signalling, which leads to excessive growth of intestinal stem cells and ultimately to an increased risk of gastrointestinal cancer,” says Bottcher.
With the help of this high-resolution technique, the researchers have also been able to study rare cell types in the intestine, for example, hormone-secreting cells. Among their findings, they were able to show that an unhealthy diet leads to a reduction in serotonin-producing cells in the intestine. This can result in intestinal inertia or increased appetite. Furthermore, the study showed that the absorbing cells adapt to the high-fat diet, and their functionality increases, thus directly promoting weight gain. Important basic research for non-invasive therapies. These findings lead to a new understanding of disease mechanisms associated with a high-calorie diet.
