Brain-Gut Axis at the Synapse: Enteric and Central Synaptic Plasticity in Functional GI Disorders

Functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome, functional dyspepsia, and chronic visceral pain syndromes, affect a substantial proportion of the global population and are characterized by altered gut motility, visceral hypersensitivity, and frequent comorbidity with anxiety, depression, and stress-related disorders. Increasing evidence positions these conditions as disorders of the brain-gut axis, in which bidirectional signaling between the enteric nervous system, vagal and spinal afferents, and central autonomic and limbic circuits is disrupted. At the heart of this dysregulation lie synaptic alterations: maladaptive plasticity within enteric ganglia and central pain and emotional networks shapes how visceral signals are generated, transmitted, and interpreted. Despite clear clinical relevance, the synaptic mechanisms linking peripheral and central nervous system changes in FGIDs remain only partially understood, limiting the development of targeted, mechanism-based therapies.

This Research Topic aims to advance understanding of how synaptic plasticity within the enteric nervous system and central brain-gut circuits contributes to the pathophysiology of functional gastrointestinal disorders. We seek studies that dissect the cellular and molecular mechanisms by which enteric, vagal, spinal, and supraspinal synapses adapt under conditions of stress, inflammation, dysbiosis, or visceral injury, and how these adaptations drive visceral hypersensitivity, motility dysfunction, and associated affective symptoms. Contributions exploring neurotransmitter and neuropeptide signaling, glial-neuronal interactions, microbiota- and metabolite-driven modulation of synaptic function, and central sensitization in pain and emotional circuits are particularly welcome. We also encourage translational and clinical work that links synaptic mechanisms to biomarkers, neuroimaging signatures, and emerging therapeutic strategies, including neuromodulation, pharmacological targeting of synaptic pathways, and microbiota-based interventions, to improve diagnosis and treatment of FGIDs.

We invite contributions spanning preclinical, translational, and clinical research that address synaptic plasticity within the brain-gut axis in functional gastrointestinal disorders. Topics of interest include, but are not limited to:
• Synaptic plasticity within the enteric nervous system in health and disease
• Vagal and spinal afferent signaling and central sensitization in visceral pain
• Plasticity in central autonomic, limbic, and pain-processing circuits in FGIDs
• Neurotransmitter and neuropeptide signaling at brain-gut synapses (serotonin, glutamate, GABA, CGRP, others)
• Enteric and central glial contributions to synaptic function and visceral hypersensitivity
• Microbiota, microbial metabolites, and immune-mediated modulation of synaptic plasticity
• Stress, HPA axis, and emotional circuit involvement in FGID pathophysiology
• Neuroimaging and electrophysiological biomarkers of brain-gut synaptic dysfunction
• Pharmacological, neuromodulatory, and microbiota-targeted therapeutic strategies

We encourage a wide range of submissions, including original research, methods papers, brief research reports, data reports, systematic reviews, mini reviews and perspectives.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review

Keywords: Brain-gut axis, Enteric nervous system plasticity, Visceral hypersensitivity, Functional gastrointestinal disorders, Central sensitization

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.