Targeted Magnetic Nanodiscs for Wireless Causal Manipulation of Gut-Brain Circuits

Abstract

Causal manipulation of gut-brain neural circuits empowers studies of metabolism and interoception. However, the anatomy and cytoarchitecture of peripheral ganglia relaying gut-brain circuits pose challenges to deployment of optical or electrical stimulation probes. To enable implant-free, cell-type specific, and temporally precise control of defined gut-brain pathways, we develop a neuromodulation platform based on magnetic nanodiscs (MNDs) targeted to peripheral neurons via genetically delivered anchoring moieties. The anchored MNDs selectively transduce externally applied weak magnetic fields to mechanical torque, thereby activating endogenous mechanosensitive pathways in specified cell types with sub-second latency. When targeted to nodose ganglia neurons expressing oxytocin or glucagon-like peptide 1 receptors, MND-mediated stimulation enables robust and reversible activation of gut-brain signaling, which engages hindbrain satiety circuits and regulates feeding behavior. These findings establish MND-mediated stimulation as a genetically targetable, implant-free strategy for modulating gut-brain neural circuits and highlight its potential in studies of brain-body physiology and bioelectronic medicines.