Noninvasive Vagus Nerve Electrical Stimulation for Immune Modulation in Sepsis Therapy.

Summary

In a murine sepsis model, ingestible piezoelectric particles activated by low-intensity ultrasound stimulated vagal afferents, engaging the cholinergic anti-inflammatory pathway. This neuromodulatory approach reduced systemic inflammation, mitigated organ injury and weight loss, and improved survival, suggesting a feasible, noninvasive bioelectronic therapy for sepsis.

Key Findings

• Ultrasound-activated piezoelectric gastric particles stimulated vagal afferents via TRPV1 targeting.
• Neuromodulation reduced systemic inflammation, tissue injury, and weight loss in murine sepsis.
• Intervention improved survival by modulating splenic immune cell responses through the CAIP.
• Approach is noninvasive and compatible with portable ultrasound with minimal thermal effects.

Clinical Implications

Not yet ready for clinical use, but points to bioelectronic vagal modulation as an adjunctive strategy for sepsis. Encourages early-phase safety and feasibility trials of ultrasound-driven neuromodulation.

Limitations

• Preclinical mouse data without human validation; safety, dosing, and biodistribution of particles remain unknown
• Comparative effectiveness versus standard sepsis therapies and long-term outcomes were not assessed

Future Directions

Conduct GLP toxicology, biodistribution, and dose-optimization studies, followed by first-in-human feasibility trials of ultrasound-driven vagal neuromodulation in sepsis or endotoxemia.