Vagus nerve–driven microbiota homeostasis: a promising integrative add-on therapy for neurodevelopmental disorders

Éric Azabou, Pierre-Yves Frouin, M. Bellaïche, Irina Duff, Guillaume Bao, Amelie Pillot, Sara Mehlal, Jean Bergounioux, Peter S. Staats, Claire-Marie Rangon

Over the past two decades, the conceptualization of neurodevelopmental disorders (NDDs) has undergone a profound transformation, shifting from a primarily brain-centric framework toward a systems-level perspective that integrates peripheral physiological processes. Among these, the gut microbiota has emerged as a critical determinant of neurodevelopmental trajectories. Through its involvement in immune modulation, metabolic signaling, and neural communication, the microbiota–gut–brain axis (MGBA) exerts a pervasive influence on brain maturation and function. A growing body of evidence indicates that early-life disruptions of microbiota composition—commonly referred to as dysbiosis—are associated with an increased risk of NDDs, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and epilepsy. These disruptions are frequently driven by environmental exposures such as antibiotic use, cesarean delivery, dietary patterns, and psychosocial stress. Despite the expanding recognition of these associations, current therapeutic strategies aimed at restoring microbiota balance, including probiotics and fecal microbiota transplantation, have yielded inconsistent and often transient results. In this context, Vagus Nerve Stimulation (VNS), particularly in its non-invasive forms (nVNS), has emerged as a promising approach capable of modulating environmental exposures through the host-centered regulatory mechanisms of the MGBA. By influencing autonomic tone, activating the cholinergic anti-inflammatory pathway, and modulating neurotransmitter systems, nVNS may restore microbiota homeostasis while simultaneously improving neurodevelopmental outcomes. This article provides a comprehensive and integrative review of the mechanistic, preclinical, and clinical evidence supporting the role of nVNS as a microbiota-modulating intervention. We further discuss its potential as a safe, cost-effective and promising therapeutic strategy for neurodevelopmental disorders, with a particular emphasis on pediatric populations.