Stretchable Sensor-Integrated Microfluidic Chip for Monitoring Fatty Acid-Enhanced Serotonin Release from the Intestinal Epithelium

High-fat foods are decomposed into fatty acids during digestion and absorption, primarily occurring in the gastrointestinal tract, and numerous studies have indicated that long-term high-fat diets significantly increase the incidence of intestinal disorders. As a critical intestinal hormone, serotonin (5-hydroxytryptamine, 5-HT) is involved in regulating intestinal peristalsis, secretion, and visceral sensitivity. However, due to the lack of methods capable of reproducing intestinal mechanical activities and in situ monitoring of 5-HT levels, the influence of high-fat diets on intestinal 5-HT release remains unclear. Herein, we presented a deformable peristalsis-mimicking intestinal epithelium chip with a built-in stretchable electrochemical sensor for in situ and quantitative 5-HT detection. Two high-fat diet models were established by pretreating the intestinal epithelium with saturated fatty acid (palmitic acid, PA) and unsaturated fatty acid (oleic acid, OA), respectively. Both PA and OA could promote epithelial 5-HT synthesis and increase 5-HT release during intestinal motility, while OA exhibited a stronger stimulatory effect on 5-HT release than PA, which might be associated with the OA-enhanced intestinal epithelial barrier. These results provide important insights into the differential roles of saturated and unsaturated fatty acids in regulating intestinal function.