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.