New tools to study the intestine

February 11, 2019

The intestine is an extremely complex organ.  There are the muscle cells that control motility, the immune cells that protect against pathogens, the symbiotic microbes, and the enteric (or intestinal) nervous system that sends and receives signals from the brain.  And then, there is the most basic component of the intestine, the actual lining of the intestine, which is the part that comes in direct contact with food moving through the digestive system.  The lining itself is also complex.  It is made up of many different types of cells that each have a specific and important function.

Dr. James Wells and colleagues recently developed a new way to produce enteroendocrine cells in the laboratory.  Approximately 1% of the cells in the intestinal lining are enteroendocrine cells.  They secrete hormones and receive signals that effect hunger, satiety, and metabolism.  The cells made using this new method have the genes turned on to produce ghrelin, GIP, motilin, neurotensin, secretin, somatostatin, substance P, serotonin, VIP, INSL5, and GLP-1.  These are all genes that are expressed in normal enteroendocrine cells!

So the cells look like true enteroendocrine cells, but do they act like normal enteroendocrine cells?  The answer is yes!  If functioning properly, these cells should change the hormones and signals they produce in response to nutrients, in the same way that your body signals for digestion to start when you eat food.  Researchers fed the cells a cocktail of nutrients including glucose and amino acids, the building blocks for protein, and they found that the level of GIP increased and ghrelin decreased.  This is exactly what happens in the body.  When you eat, the enteroendocrine cells sense sugars and fats and secrete GIP in response.  They also reduce the amount of ghrelin produced to send a signal of satiety.

From the data scientists have collected so far, these new cells look like the real deal.  That means we have a new tool to study how the body responds to dietary changes, which could lead to treatments for metabolic diseases like diabetes and insights into gastrointestinal disorders like irritable bowel syndrome.

If you’re interested in the scientific details, check out the following scholarly article.

Sinagoga KL, McCauley HA, Múnera JO, Reynolds NA, Enriquez JR, Watson C, Yang HC, Helmrath MA, Wells JM. Deriving functional human enteroendocrine cells from pluripotent stem cells. Development. 2018 Oct 1;145(19).


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