Electro-microbial interplay in the gut–brain axis: An emerging paradigm for gut microbiota modulation via vagus nerve stimulation

Dec 20, 2025Current opinion in pharmacology

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

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Gut-Brain Axis on OpenScience ↗PubMed ↗DOI ↗

Abstract

Vagus nerve stimulation (VNS) is associated with changes in gut microbiota composition and function.

The gut-brain axis facilitates communication between the gastrointestinal tract and the brain, primarily through the vagus nerve.
VNS may alter the functional output of gut microbiota, potentially impacting the progression of central nervous system disorders.
Gut microbiota and their metabolites, such as short-chain fatty acids, can influence vagal activity via feedback mechanisms.
This interaction involves complex neural, immune, and metabolic pathways.
Understanding these mechanisms could lead to innovative therapeutic strategies targeting the gut-brain interface.

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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.