Current opinion in pharmacologyDec 20, 2025

Electrical and microbial interactions in the gut-brain connection: New ways to influence gut microbes through stimulation of the nerve linking gut and brain

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Vagus nerve stimulation may interact bidirectionally with gut microbiota through neural, immune, and metabolic pathways in the gut-brain axis.

Evidence

This is a systematic review of studies on VNS, gut microbiota, microbial metabolites such as short-chain fatty acids, and vagal feedback in central nervous system disorder contexts.

Caveat

As a mechanistic review, it synthesizes emerging evidence but does not provide a single tested clinical protocol or pooled efficacy estimate.

Simplified

The treatment of central nervous system disorders remains a clinical challenge, highlighting an urgent need for innovative therapeutic strategies. The gut-brain axis represents a complex bidirectional communication network between the gastrointestinal tract and the brain, with the vagus nerve serving as a critical pathway for signal transmission. Vagus nerve stimulation (VNS), an established therapy for drug-resistant epilepsy and depression, has been shown to modulate the composition and functional output of gut microbiota, which in turn influences disease progression. Concurrently, gut microbiota and their metabolites such as short-chain fatty acids can regulate vagal activity through feedback mechanisms. This bidirectional interaction operates through neural, immune and metabolic pathways. This review provides a systematic review of the mechanisms through which VNS influences gut microbiota, and how microbial products feedback to regulate vagus nerve activity and the integrated pathways underlying this cross-talk, for the sake of providing insights into novel therapeutic approaches targeting the gut-brain interface.