image: intestinal stem cells green, cell division red.
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Loan: Helmholtz Munich / Anika Butcher

The gut is able to maintain our energy balance; it is a master of responding quickly to changes in food և nutrient balance. It does this with the help of intestinal cells, which, among other things, specialize in absorbing nutrients or releasing hormones. In adults, the gut cells regenerate every five to seven days. The ability to constantly rejuvenate and develop all types of intestinal cells from intestinal stem cells is crucial to the natural adaptation of the digestive system. However, a high-fat, high-fat diet disrupts this adaptation and can lead to obesity, type 2 diabetes, and gastrointestinal cancer.

The molecular mechanisms behind this discrepancy are the research field of Heiko Likert խմբի and his group at the Helmholtz University of Technology in Munich. Scientists believe that intestinal stem cells play a special role in poor adaptation. Using the mouse model, the researchers compared the effects of a sugar-fat diet with those of a control group.

From a high-calorie diet to a high risk of gastrointestinal cancer
“The first thing we noticed was that the small intestine was greatly enlarged by a high-calorie diet,” said study leader Anika Butcher. “Helmholtz Munich’s team of computer biologists Fabian Theis then profiled 27,000 gut cells from a high-fat / high-sugar / sugar-fed diet of mice. “Using new machine learning techniques, we found that in mice on an unhealthy diet, intestinal stem cells divide and differentiate much faster.” Researchers believe that this is due to the regulation of the corresponding signaling pathways, which is associated with accelerated tumor growth in many types of cancer. “This can be a strong connection. “Diet affects metabolic signals, which leads to an overgrowth of intestinal stem cells and, ultimately, an increased risk of gastrointestinal cancer,” says Butcher.

Using this high-resolution technique, researchers were also able to study rare cell types, such as 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 gut. This can lead to intestinal inertia (typical of diabetes) or increased appetite. Moreover, the study showed that the absorbing cells adapt to the fat diet, և their functionality increases, thus directly contributing to weight gain.

Important research for non-invasive therapy
These and other findings from the study lead to a new understanding of the mechanisms of disease associated with a high-calorie diet. “What we have found is crucial to the development of alternative non-invasive therapy,” said study leader Hayko Likert, summing up the results. To date, there is no pharmacological approach to obesity to prevent, stop or reverse diabetes. Bariatric surgery alone can lead to permanent weight loss and can even lead to diabetes remission. However, these surgeries are invasive, irreversible, and costly for the health care system. New non-invasive therapies may occur, for example, at hormone levels by targeted regulation of serotonin levels. The research team will explore these and other approaches in future studies.

About the people
Hayko Likert և Anika Butcher is conducting research at the Helmholtz Diabetes Center in Munich. They specialize in developing rehabilitative treatment approaches for the many common diseases associated with intestinal dysfunction. Likert heads the Diabetes and Regeneration Research Institute and is a professor at the Technical University of Munich (TUM). Both are scientists from the German Center for Diabetes Research (DZD).

The current study is published as a cover Nature’s metabolism.

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