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How a gut “feeling” helps digestion

Research using a mouse model provided insight into how cells sense the chemical and physical properties of gut contents to regulate digestion. As food moves through the gastrointestinal (GI) tract, digestive organs break the food—using motion and digestive juices—into parts small enough for the body to absorb and use for energy, growth, and cell repair, while moving waste down and out of the body. These digestive activities require the cells lining the GI tract to be able to sense the chemical and physical properties of the contents and translate these properties into signals to modulate the function of and transit through the gut. Previous studies identified a subset of enteroendrocine cells (EECs) in the GI tract that have Piezo2, a protein which is also found in a type of skin cell responsible for the sense of touch. In the GI tract, these cells interact closely with the contents of the gut, but it was unknown if and how these cells might act as sensors to “touch” and “feel” gut contents and affect gut function in response.

Using genetic techniques, the scientists identified the EEC Piezo2 cells in the mouse gut and investigated their role. When the EEC Piezo2 cells were stimulated, the scientists observed an increase in the frequency of gut contractions, suggesting that these cells had a role in moving the gut. When the Piezo2 protein was missing from these cells, the scientists were no longer able to affect contraction frequency. To further study the role of EEC Piezo2 cells, the scientists observed digestion in mice genetically altered to be missing Piezo2. In comparison to mice with the protein, mice lacking Piezo2 were unable to regulate motility in response to gut contents. Instead, small-sized indigestible beads, given by mouth to the animals, moved right through and were not distributed appropriately throughout the gut. Additionally, it took longer for these mice to move large-sized waste pellets through their GI tract. Collectively, these results indicate that the subpopulation of EEC cells with Piezo2 is critical to the mechanosensory system of the mouse GI tract to sense gut contents and regulate GI motility in response.

Disruption of gut motility in humans can lead to abdominal pain and changes in bowel movements, such as constipation or diarrhea, and has been implicated in disorders of the GI like irritable bowel syndrome. Further research is needed to explore whether EEC Piezo2 cells are present and act similarly to detect gut contents in humans, whether these cells are disrupted in GI diseases, and if stimulation of these cells can contribute to improvements of symptoms. This discovery provides a new avenue to explore and could help development of novel strategies to treat people with GI disorders.

Treichel AJ, Finholm I, Knutson KR, …Beyder A. Specialized mechanosensory epithelial cells in mouse gut intrinsic tactile sensitivity. Gastroenterology 162, 535-547.e13, 2022.

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