The Potential Enteroendocrine Cell Breakthrough

A close up of an enteroendocrine cell

For the last several decades, the number of overweight and obese individuals has risen to epidemic proportions. At the same time, chronic illnesses such as diabetes are also on the rise. These developments have encouraged researchers and scientists to investigate innovative ways to better manage these conditions. But to date, most therapies have had limited benefits or are associated with unwanted side effects. But based on recent discoveries, new options of care may be just around the corner. Scientists have identified several types of enteroendocrine cells that could provide new answers. If enteroendocrine cell function can be better defined, new options of care for a variety of conditions may be available.

While there are several types of enteroendocrine cells, each has the potential to stimulate the release of various hormones. It is these hormones that could then be used to treat gastrointestinal disorders related to digestion and metabolism. While further delineating enteroendocrine cell function might normally take years, new techniques are expected to speed up this process significantly. For this reason, many researchers are excited about the potential that these new cells could have. Scientists have a long way to go, but the future for enteroendocrine cells looks quite bright.

“There’s been interest in exploiting human intestinal stem cells and [enteroendocrine] cells to treat disease. But the field is still in a nascent stage. This will open new avenues of discovery.” – David Breault, MD, Ph.D., Associate Chief of the Division of Endocrinology, Boston Children’s Hospital

What Are Enteroendocrine Cells?

When it comes to intestinal cells, hundreds of millions exist. In this regard, enteroendocrine cells make up only 1% of all intestinal cells present. But that doesn’t mean there not significant in number of effects. In fact, various types of enteroendocrine cells are believed to represent the largest collection of endocrine cells in the body. And based on ongoing research findings, enteroendocrine cell function oversees a number of intestinal processes. To date, these cells are known to produce more than 15 different hormones that regulate dozens of cellular activities. They also appear to play a role in immune system functioning as well. Without a doubt, these cells are important, especially when it comes to metabolism and digestive health.

Various types of enteroendocrine cells exist throughout the intestinal lining. When nutrients enter the intestine, such as glucose and amino acids, these cells produce highly specific hormones. These hormones then trigger other intestinal cells to perform in specific ways. At the same time, microbes in the gut also guide enteroendocrine cell function. Different metabolites of different microbes determine which hormones these cells release. Depending on the situation, this may alter digestion and food absorption, or it could affect appetite or insulin production. This is why these cells may offer insights about managing conditions like diabetes. In short, these enteroendocrine cells play a significant intermediary role between what we eat and how our bodies react.

“The ultimate goal would be to identify a medication that induces the secretion of multiple hormones at once. This most likely mimics what happens in the body after a meal and may prevent side effects that could occur with the overproduction of just one hormone.” – Daniel Zeve, MD, Ph.D., Endocrinologist

Future Uses for Enteroendocrine Cell Function

The reason scientists are enthusiastic about enteroendocrine cell function relates to their hormone production capacities. For example, for the patient with Type I diabetes, manipulation of specific types of enteroendocrine cells could result in better insulin production. For those who are obese, hormones that promote feelings of satiety could better curb appetite. Plus, in this latter example, hormones produced by enteroendocrine cells would be less likely to have side effects. Because they tend to produce multiple hormones in a more balanced manner, the effect could be smoother and more effective.

A cell just splashing around, having fun
A breakthrough in enteroendocrine cell function could be key in fighting diabetes and obesity.

Of course, diabetes and obesity are not the only conditions that might be better served by enteroendocrine cell function. These cells are also involved in the immune response related to intestinal infections. Different types of enteroendocrine cells produce hormones and cytokines that can modulate an immune response. Thus, a microbe that is pathogenic stimulates a different enteroendocrine cell function than one that is benign. Therefore, these cells might be useful in managing autoimmune intestinal disorders and perhaps even irritable bowel syndrome. And ultimately, greater knowledge about these cells could help us determine how to create a healthy microbiome overall. (Read more about the optimal diet for a healthy gut biome in this Bold story.)

“We trust our gut with the food we eat. Sugar has both taste and nutritive value and the gut is able to identify both.” – Diego Bohórquez, Associate Professor of Medicine and Neurobiology, Duke University School of Medicine

New Techniques Advancing Enteroendocrine Cell Insights

While scientists have known about different types of enteroendocrine cells previously, new research techniques are accelerating their knowledge. Thanks to new approaches, researchers no longer have to go through lengthy genetic protocols to test hypotheses. Instead, they have been able to create small “organoids” composed of several cells upon which to test tissue responses. After taking adult intestinal biopsies that contain enteroendocrine cells, organoids are created. Different chemicals are then applied to these organoids to determine different enteroendocrine cell function. Using this method, researchers have already identified ways to stimulate the production of specific hormone combinations.

While organoid techniques have accelerated insights about enteroendocrine cell function related to hormones, they have helped in other ways. Other researchers have employed this same technique to study the interaction between different types of enteroendocrine cells and the brain. As it turns out, enteroendocrine cells not only release slow-acting hormones but fast-acting neurotransmitters as well. In these studies, scientists discovered that mice without taste buds could still distinguish between sugar and artificial sweeteners. As a result of enteroendocrine cell function, the lack of taste didn’t impair the mice’s ability to tell the difference. Assumedly, because enteroendocrine cells respond to nutrient value, they somehow signaled the brain regarding the quantitative difference in the sweeteners.

The Tip of the Enteroendocrine Cell Iceberg

When it comes to digestive health, scientists appreciate that they are just beginning to understand how enteroendocrine cell function works. Not only are there multiple types of enteroendocrine cells, but each type regulates different metabolic and digestive functions. However, they provide a key to better understanding many gastrointestinal disorders. And they perhaps hold the key to a better comprehension of microbiome variances. Therefore, we can likely expect to see much more research in this area in the years to come.


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