Our diet can change the structure and functionality of our intestines, and have a long-term impact on our metabolism. A study conducted by a team of researchers at the Carnegie Institution for Science in USA, and published in October 2018, supports this view.
Dietary nutrients trigger structural changes in body organs, such as the intestine and ovaries, which can have lasting impact on metabolism, according to Carnegie’s Rebecca Obniski, Matthew Sieber, and Allan Spradling. Their work, aimed at understanding why and how such diet-induced changes occur, was published by Developmental Cell, and is based on experiments with fruit flies (Drosophila melanogaster), the model organism best suitable to study diet-induced structural changes that are likely to be similar to humans.
The development, growth, regeneration and reproduction of every animal relies on constant structural and functional maintenance of its tissues and organs. Homeostasis of most adult organs depends on small populations of tissue specific stem cells that can self-renew and at the same time generate differentiated cells to replace the aged or damaged ones. One of the most rapidly renewing tissues is the lining of the small intestine, outpacing all other tissues in the vertebrate body. The drosophila intestine bears close resemblance to the mammalian intestine, in structural organization as in signaling mechanisms responsible for tissue homeostasis and regeneration.
The drosophila and mammalian intestines are maintained throughout adulthood by intestinal stem cells, or ISCs (Ohlstein B., Spradling A. 2006). The ISCs reside on the basal surface in direct contact with the basement membrane, which separates the gut epithelium from the surrounding visceral muscles. ISCs divide asymmetrically to generate new stem cells and transient progenitors called enteroblasts (EBs). The immature EBs commit towards differentiation and produce absorptive enterocytes (ECs) and hormone-secreting enteroendocrine (EEs) cells.
What does this mean? It shows that a reduced nutrient uptake, especially early in life, similar to the low-cholesterol diet in fruit flies, can trigger changes in intestinal structure and metabolism with long-term repercussions. These changes persist for quite a while, even on different diets, and can lead to metabolic health problems. "Children born to malnourished mothers often struggle with obesity later in life and our findings could explain the physiology of why that happens," Obniski explained.
By understanding how nutrient availability affects intestinal function, we could find ways to use diet to mitigate disease and even aging in adults. For example, understanding the signaling-based mechanism underlying this developmental metabolic programming helps explain why a high-fat diet can promote the formation of certain types of intestinal cancer.
"The intestines are the organs most-directly responsible for balancing an organism's long- and short-term needs with its nutritional environment," Spradling said. "The power of the fruit fly as a model system allows one of the complex mechanisms that balance these needs with diet to be understood at a mechanistic level, something that is very difficult to do directly in mammalian systems or in human patients."
The stem cells could be thought of as blank templates that are eventually programmed to become either hormone-producing or nutrient-handling cells. The authors found that dietary nutrients influence this programming, and that the younger the animals are, the stronger is the influence.
Dietary cholesterol seems to be particularly important, being able to alter the cellular reprogramming driving the production of new specialized cells from stem cells. The effect of cholesterol is to bias the programming of more new blank stem cells into hormone-producing cells rather than nutrient-handling cells. Conversely, decreasing dietary cholesterol results in more nutrient-absorbing cells and fewer hormone-producing cells. Furthermore, the authors were able to delineate the signaling pathways through which cholesterol causes these changes in cell fates, and highlight how closely related this mechanism is to the way human intestinal cells regulate cholesterol production.
More information: Rebecca Obniski et al, Dietary Lipids Modulate Notch Signaling and Influence Adult Intestinal Development and Metabolism in Drosophila, Dev. Cell (2018).
Author: Sebastian I. Florescu