Orally Ingested Self‐Powered Stimulators for Targeted Gut–Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders

Abstract Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self‐powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO₃ (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet‐induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap‐sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut–brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3‐week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle‐based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy‐to‐administer intervention holds potential for addressing other intracerebral neurological diseases.