The intestine is essential for maintaining the energy balance and is a master at reacting quickly to changes in diet and nutrient balance. He succeeds in doing this with the help of intestinal cells which, among other things, specialize in the absorption of food components or the release of hormones.
In adults, 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 high-sugar and high-fat diet disrupts this adaptation and can contribute to obesity, type 2 diabetes, and gastrointestinal cancer. The results were published in Nature Metabolism.
The molecular mechanisms of this mismatch are part of the research area of Heiko Lickert and his group at Helmholtz Munich and the Technical University of Munich. Scientists believe that intestinal stem cells play a unique role in the maladjustment. Using a mouse model, the researchers examined the effects of a high-sugar and high-fat diet and compared this with a control group.
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From high calorie diets to increased risk of gastrointestinal cancer
“The first thing we noticed was that the high-calorie diet made the small intestine grow in size,” says study director Anika Bottcher. “Together with the team of computer biologists from Fabian Theis at Helmholtz Munich, we then profiled 27,000 intestinal cells from control diets and mice that were fed a high-fat / high-sugar diet. Using new machine learning techniques, we found that intestinal stem cells divide and differentiate. “In mice with an unhealthy diet, this is significantly faster.” The researchers suspected that this is due to an upregulation of the relevant signaling pathways, which in many types of cancer accelerate associated with tumor growth.
“This could be an important link: Diet influences metabolic signal transmission, 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 technology, the researchers were also able to study rare cell types in the intestine, such as hormone-secreting cells. Among other things, they were able to show that an unhealthy diet leads to a reduction in serotonin-producing cells in the intestine. This can lead to sluggishness in the bowel (typical of diabetes mellitus) or increased appetite. In addition, the study showed that the absorbent cells adapt to the high-fat diet and their functionality increases, which directly promotes weight gain.
Important basic research for non-invasive therapies
These and other findings from the study lead to a new understanding of the disease mechanisms in connection with a high-calorie diet. “What we have found is of crucial importance for the development of alternative, non-invasive therapies,” study leader Heiko Lickert summarizes the results. Unfortunately, there is no pharmacological approach to preventing, stopping, or reversing obesity and diabetes. Only bariatric surgery results in permanent weight loss and can even lead to diabetes in remission.
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However, these surgeries are invasive, irreversible, and costly to the healthcare system. Novel non-invasive therapies could, for example, take place at the hormonal level through targeted regulation of the serotonin level. The research group will pursue these and other approaches in further studies.
