ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Nature Cell Biology 20,909–916 (2018)

Produced by scattered Enteroendocrine cells (EECs)found along the length of the intestinal epithelium, gut hormones generate signals related to the rate of nutrient absorption, the composition of the luminal milieu and the integrity of the epithelial barrier. To study these rare cells, these authors combined the technology of single-cell sequencing (Science Breakthrough of the Year 2018) with a method to determine the age of each cell. As a result, they could study the development of EECs.

Fewer than 1% of the cells in the intestinal lining are EECs. Scattered throughout the stomach and intestine, EECs control a wide range of physiological processes linked to metabolism. Products of food digestion (i.e., glucose, amino acids and fatty acids) and microbial fermentation act as stimuli for local EECs. Such hormones act as the GI tract communication and coordination with the brain and pancreas and the more distant parts of the digestive tract. In response to defined stimuli, different EECs produce different hormones, which coordinate movement of intestinal muscles, stimulate the repair of the intestine’s protective cell layer, induce hunger or satiety or promote the secretion of insulin. Indeed, one of the most successful treatments for diabetes is based on the gut hormone Glucagon-like peptide-1 (GLP1).

Similar to the growth plate columns, EECs are continuously produced and live for several weeks, while changing their position along the villi-crypts structures. While moving and aging, EECs change their hormone expression. BMP4 signals alter the hormone expression profiles of individual EECs to resemble those found in the villus. Accordingly, BMP4 induces hormone switching of EECs migrating up the crypt–villus axis.

Once we understand the signals that control hormone expression, we may be able to stimulate the intestine to differentially generate specific hormones to treat diabetes, obesity or inflammatory bowel disease. But also, bariatric surgery rearranges intestinal anatomy, resulting in markedly elevated postprandial concentrations of GLP 1 and peptide YY, which contribute substantially to postsurgical weight loss and resolution of T2D mellitus.