The gut is important for maintaining our energy balance; it is a master of responding quickly to changes in the balance of food and nutrients. 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 intestinal stem cells is essential for the natural adaptation of the digestive system. However, a “high-fat” diet high in sugar 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 և 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 with a high-calorie diet, the small intestine grows larger. With a team of Fabian Theis computational biologists in Helmholtz, Munich, we then profiled 27,000 gut cells from a controlled, high-fat / sugar-fed diet. “Using new machine learning techniques, we found that in mice on an unhealthy diet, intestinal stem cells divide and differentiate much faster.”
Anika Butcher, head of research
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 could 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 intestinal 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 research findings lead to a new understanding of the mechanisms of disease associated with a high-calorie diet. “What we have found is crucial for the development of non-invasive alternative therapy,” said study leader Hayko Likert, summing up the results. To date, there is no pharmacological approach to preventing, stopping, or counteracting obesity. 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 the hormone level 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.
Helmholtz Zentrum München – German Center for Environmental Health Research
Alilu, A. et al. (2021) Changes in intestinal stem cell function due to diet are the basis of obesity և prediabetes in mice. Nature’s metabolism. doi.org/10.1038/s42255-021-00458-9: