A Balloon Electrochemical Sensor for Conformal Interfacing With Intestinal Wall and Real‐Time Monitoring of Serotonin Release

Gut function is closely modulated by the synchronized mechanical activities of intestinal wall and luminal microbial-derived metabolites, and their influences are speculated to converge on serotonin (5-HT) signaling pathways. Existing knowledge mainly focuses on the isolated effect of mechanical or microbial factors on the ultimate intestinal 5-HT levels. However, it remains unclear how these coexisting factors interplay and modulate 5-HT release during dynamic peristaltic activity. Herein, leveraging the mechanical deformability and in situ measurement of stretchable electrodes, this study presents a balloon electrochemical sensor to seamlessly interface with the gut lining, initiate mechanical distension, and monitor ensuing 5-HT overflow. These tailored sensors allow systematic quantification of 5-HT release from intestinal cells and tissues exposed to mechanical distension and short-chain fatty acids (SCFAs). This results reveal that mechanical stimuli evoke Piezo2-mediated transient 5-HT release from enterochromaffin cells of the intestine. While, SCFAs stimulation triggers transient 5-HT release through G-protein coupled receptor (GPCR) activation, and prolonged SCFAs exposure enhances 5-HT biosynthesis and mechanosensitivity. These findings provide direct evidence to decipher how mechanical and microbial factors synergistically potentiate the 5-HT secretion in peristaltic intestine, as well as crucial perspectives for the complex mechano-chemical coupling in signal transduction.