A new study published in Nature Metabolism has found a link between diet, intestinal cell changes and disease.
The intestine has to react quickly to changes in nutrition and nutrient balance. One of the ways it does so is with intestinal cells that are specialised 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 molecular mechanisms behind this maladaptation are the research area of this study. Intestinal stem cells are thought to play a special role in maladaptation, and to investigate this, the researchers used a mouse model to compare the impacts of a high-sugar and high-fat diet and with a control group.
“The first thing we noticed was that the small intestine increases greatly in size on the high-calorie diet,” said study leader Anika Böttcher. “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 signaling pathways, which is associated with an acceleration of tumor growth in many cancers. “This could be an important link: Diet influences metabolic signaling, which leads to excessive growth of intestinal stem cells and ultimately to an increased risk of gastrointestinal cancer,” says Böttcher.
Using this high-resolution technique, the researchers have also been able to study rare cell types in the intestine, 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 intestine. This can result in intestinal inertia (typical of diabetes mellitus) or increased appetite. Furthermore, the absorbing cells were shown to adapt to the high-fat diet, increasing functionality and thus directly contributing to weight gain.
The study findings enable a new understanding of disease mechanisms associated with a high-calorie diet. “What we have found out is of crucial importance for developing alternative non-invasive therapies,” said study leader Heiko Lickert.
Presently, there is no pharmacological approach to prevent, stop or reverse obesity and diabetes. Only bariatric surgery causes permanent weight loss and can even lead to remission of diabetes. However, these surgeries are invasive, non-reversible and costly to the healthcare system. Novel non-invasive therapies could happen, for example, at the hormonal level through targeted regulation of serotonin levels. This will be an avenue of future research for the group.
Source: EurekAlert!
