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Cited by 149Gut microbiota and healthGastrointestinal motility and disordersTryptophan and brain disorders

Beyond the gut: decoding the gut–immune–brain axis in health and disease

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Park, John Chulhoon, Chang, Leechung, Kwon, Ho-Keun, Im, Sin-Hyeog·2025·Cellular & Molecular Immunology
DOI 10.1038/s41423-025-01333-3PMC PMC12575876
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Abstract

Emerging research underscores the pivotal role of the gut–immune–brain axis, a dynamic bidirectional communication system involving intricate interactions between the gut microbiota, immune responses, and the central nervous system. Gut microbes and their metabolites have profound effects on immune and neurological homeostasis, influencing the development and function of multiple physiological systems. Disruption of the composition of the gut microbiota and barrier integrity has been implicated in various neurological and psychiatric disorders, including autism spectrum disorder, Alzheimer’s disease, Parkinson’s disease, depression, and anxiety. Most insights into these host–microbiota interactions come from preclinical models, revealing both the complexity and potential therapeutic opportunities of the gut–brain communication pathways. This review synthesizes the current understanding of these intricate interactions, exploring how microbiota-driven modulation of the gut and brain barriers, immune signaling, and neuronal pathways, such as those through the vagus nerve, contributes to health and disease. We further explore therapeutic implications, including personalized precision microbiota interventions, microbiome-derived biomarkers, and barrier-strengthening strategies. Advancing this field offers transformative potential for developing innovative, personalized therapies tailored to individual microbiomes and immune profiles, ultimately redefining clinical approaches to neurological and immune-mediated diseases.

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  • Multiple biological mechanisms contribute to microbiota-gut-brain axis signaling, including immune modulation, neural communication via the autonomic nervous system and vagus nerve, microbial metabolite production, and neurotransmitter synthesis and metabolism.

    “Multiple biological mechanisms contribute to MGBA signaling, including immune modulation (Park et al., 2025), neural communication via the autonomic nervous system (O'Riordan et al., 2025), particularly the vagus nerve (Cryan et al., 2019), microbial metabolite production such as bile acids, choline, and short-chain fatty acids, and the synthesis and metabolism of neurotransmitters, including γ-”

    From Psychobiotics in mental health: insights from human clinical trials via the gut-brain axis (2026) · cites this paper as Park et al., 2025

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Authors
Park, J. C., Chang, L., Kwon, H.-K., & Im, S.-H.
Affiliations
  • Pohang University of Science and Technology (KR)
  • Yonsei University (KR)
Corresponding author
  • Kwon, Ho-Keun
  • Im, Sin-Hyeog
ORCID
Venue
Cellular & Molecular Immunology
Publisher
Springer Science and Business Media LLC
Published
2025-08-14
Volume
22
Issue
11
Pages
1287-1312
ISSN
  • 1672-7681 (ISSN-L)
  • 2042-0226
DOI
10.1038/s41423-025-01333-3
PMC
PMC12575876
OpenAlex
W4413115178
Cited by
149
References
379
Citations by year
2026: 132 · 2025: 17
FWCI
13.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Research Foundation of Korea (RS-2024-00345575, RS-2019-NR040072, RS-2025-00561456, RS-2024-00438443, RS-2024-00361620)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
gut-brain-immune axis, gut microbiota, microbiota metabolites, intestinal barrier integrity, neurological disorders, mental illness, autism spectrum disorder, Alzheimer's disease, Parkinson's disease, depression, anxiety, vagus nerve, microbiota-based therapy, immune signaling
MeSH terms
Gastrointestinal Microbiome, Brain-Gut Axis, Animals, Brain, Humans, Immune System

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