This study introduces a novel bioelectronic system, iMAS-SAGE, designed to modulate gut microbiota using extracellular vesicles (EVs) produced by autologous macrophages. The system leverages mechanical stimulation of hydrogel-embedded macrophages, controlled by a wireless bioelectronic controller, to boost EV production up to 20 times the normal rate. This approach aims to address the insufficient and unreliable doses of EVs produced by host immune cells to counteract deleterious effects of pathogenic gut microbiota. The iMAS-SAGE system is placed in the mesentery, a dense network of blood and lymph vessels, to ensure direct access to the gut without the need for precise targeting of affected intestinal segments. The system's wireless control allows for adjustable and repeatable EV production, making it suitable for long-term treatments. In vivo experiments in a mouse model of inflammatory bowel disease (IBD) demonstrated that iMAS-SAGE significantly improved gut microbiota composition and reduced disease severity compared to controls. The study highlights the potential of iMAS-SAGE as a platform for treating various diseases by modulating gut microbiota through autologous EVs.This study introduces a novel bioelectronic system, iMAS-SAGE, designed to modulate gut microbiota using extracellular vesicles (EVs) produced by autologous macrophages. The system leverages mechanical stimulation of hydrogel-embedded macrophages, controlled by a wireless bioelectronic controller, to boost EV production up to 20 times the normal rate. This approach aims to address the insufficient and unreliable doses of EVs produced by host immune cells to counteract deleterious effects of pathogenic gut microbiota. The iMAS-SAGE system is placed in the mesentery, a dense network of blood and lymph vessels, to ensure direct access to the gut without the need for precise targeting of affected intestinal segments. The system's wireless control allows for adjustable and repeatable EV production, making it suitable for long-term treatments. In vivo experiments in a mouse model of inflammatory bowel disease (IBD) demonstrated that iMAS-SAGE significantly improved gut microbiota composition and reduced disease severity compared to controls. The study highlights the potential of iMAS-SAGE as a platform for treating various diseases by modulating gut microbiota through autologous EVs.