The intestine is vital to maintaining our energy balance and is adept in reacting quickly to changes in nutrient balance and nutrition. It does this through intestinal cells, which are specially trained in the digestion of food ingredients and in the release of hormones. The intestinal cells of adults regenerate about every five to seven days. The capacity to continually regenerate and create all kinds of intestinal cells from stem cells in the intestinal tract is essential for the natural flexibility of the digestive system. A long-term diet high on sugar and fat may disrupt this adaptation and cause obesity, type 2 diabetes, and gastrointestinal cancer.
Heiko Lickert’s group of researchers at Helmholtz Munich, and the Technical University of Munich are studying the molecular mechanisms behind maladaptation. The scientists assume that intestinal stem cells play an important role in maladaptation. Using a mouse model, researchers examined the effects of a high-sugar , high-fat diet and compared it with the control group.
From a high-calorie diet to an the increased risk of gastrointestinal cancer
The first thing we noticed was that the small intestine grows greatly in size on the high-calorie diet. Fabian Theis, a computational biologist at Helmholtz München and I then analyzed 27,000 intestinal cell samples from mice fed a high-fat/high sugar diet. We discovered that intestinal stem cells differentiate and divide faster in mice fed an unhealthy diet by using machine learning techniques.
Anika Bottcher, Study Leader
The researchers hypothesize that this is due an increase in the activity of the relevant signaling pathways, which is connected to an increase in tumor growth in many cancers. “This could be a significant link: Diet influences metabolic signaling, which can lead to an increase in the number of intestinal stem cells and ultimately increases the risk of developing gastrointestinal cancers,” says Bottcher.
The high-resolution technique allowed the researchers to examine some of the most unusual cells in the intestinal tract. They were able to show that a poor diet could lead to a decrease in the number of serotonin-producing cells in the intestine. This may cause intestinal inertia (typical of diabetes mellitus) or an increase in appetite. The study also demonstrated that the absorbing cells respond to diets high in fat and their function increases, thereby directly promoting weight loss.
It is imperative to conduct research on non-invasive treatments
The findings and other results from the study lead to an understanding of the disease mechanisms that are associated with a high-calorie diet. Heiko Lickert, the study director, summarizes the findings by saying that “what we have discovered is crucial for developing alternative, non-invasive treatments.” There is no current pharmaceutical method to reverse or prevent diabetes and obesity. Bariatric surgery is the sole way to permanently lose weight and can even reverse the effects of diabetes. However, these surgeries are ineffective, non-reversible and costly for the healthcare system. For example, novel non-invasive therapies may be possible at the hormonal level , by targeting the regulation of serotonin levels. These and other strategies will be examined by the research group in the future research studies.
About the people
Anika Bottcher and Heiko Lickert conduct research at Helmholtz Diabetes Center in Helmholtz Munich. They are experts in the development of regenerative therapies for many common digestive disorders. Lickert is the head of the Institute for Diabetes and Regeneration Research and a professor at the Technical University of Munich (TUM). Both are scientists at the German Center for Diabetes Research (DZD).
The current study was published as an article in Nature Metabolism.
Aliluev A., and al. (2021). Diet-induced changes in the function of intestinal stem cells are the cause of obesity and prediabetes among mice. Nature Metabolism. doi.org/10.1038/s42255-021-00458-9.
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