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Institute of Metabolic Science

Metabolic Research Laboratories
 
graphical abstract summarising the paper

Research recently published (article in press) in Cellular and Molecular Gastroenterology and Hepatology (CMGH) and led by Dr Constanza Alcaino from the Gribble/Reimann group, and colleagues at the IMS-MRL and elsewhere, has for the first time, provided a complete expression and functional profile of human enterochromaffin cells which help control how our gut moves and feels.

The research team wanted to understand how these cells are activated by the nutrients we eat, and the hormones and neurotransmitters released by neighbouring cells and neurons, which can trigger the release of serotonin. Using donor tissue, they developed human intestinal organoids, or "mini guts", which replicate the intestinal epithelium in vitro. These organoids express different types of epithelial cells, which they labelled with fluorescent markers using CRISPR-Cas9 technology in order to fully characterise them using imaging and molecular biology techniques.

They discovered that the enterochromaffin cells release serotonin in response to certain signals by activating specific membrane receptors, which we know is an important process for keeping the gut healthy and working properly. Some of these findings had previously been shown in mouse models, but this study is the first to use human enterochromaffin cells. If these messages get mixed up, it can lead to gut problems like irritable bowel syndrome (IBS), so by understanding how these cells work, it might be possible to develop new treatments for these conditions.

Alcaino C, Guccio N, Miedzybrodzka EL, Quale JR, Lu T, Davison A, Smith CA, Overington E, Hernández MS-, Tabbada M, Hodge M, Bakar RB, Kay R, Shaaban A, Imig C, Reimann F, Gribble FM, Mechanisms of Activation and Serotonin release from Human Enterochromaffin Cells, Cellular and Molecular Gastroenterology and Hepatology (2025),