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Cited by 333Gut microbiota and healthTryptophan and brain disordersGastrointestinal motility and disorders

The gut microbiota-immune-brain axis: therapeutic implications

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O’Riordan, Kenneth J., Moloney, Gerard M., Keane, Lily, Clarke, Gerard, Cryan, John F.·2025·Cell Reports Medicine
DOI 10.1016/j.xcrm.2025.101982PMC PMC11970326
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Abstract

The microbiota-gut-brain axis has major implications for human health including gastrointestinal physiology, brain function, and behavior. The immune system represents a key pathway of communication along this axis with the microbiome implicated in neuroinflammation in health and disease. In this review, we discuss the mechanisms as to how the gut microbiota interacts with the brain, focusing on innate and adaptive immunity that are often disrupted in gut-brain axis disorders. We also consider the implications of these observations and how they can be advanced by interdisciplinary research. Leveraging an increased understanding of how these interactions regulate immunity has the potential to usher in a new era of precision neuropsychiatric clinical interventions for psychiatric, neurodevelopmental, and neurological disorders. The gut microbiota-immune-brain axis regulates key immune pathways influencing neuroinflammation and brain function. This review highlights how gut-immune communication impacts health and disease, emphasizing the potential of these insights to drive precision therapies for neuropsychiatric disorders.

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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 O'Riordan et al., 2025

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Cited by

Sorted by citations

Authors
O’Riordan, K. J., Moloney, G. M., Keane, L., Clarke, G., & Cryan, J. F.
Affiliations
University College Cork (IE)
Corresponding author
Cryan, John F.
ORCID
Venue
Cell Reports Medicine
Publisher
Elsevier BV
Published
2025-03
Volume
6
Issue
3
Pages
101982
ISSN
2666-3791 (ISSN-L)
DOI
10.1016/j.xcrm.2025.101982
PMC
PMC11970326
OpenAlex
W4408301706
Cited by
333
References
25
Citations by year
2026: 232 · 2025: 101
FWCI
29.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Cork Open Research Archive (University College Cork, Ireland) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Taighde Éireann – Research Ireland (SFI/12/RC/2273_P2)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRSII5_186346/NMS2068)
  • Ian's Friends Foundation
  • Saks-Kavanaugh Foundation
  • DuPont
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
gut microbiota, neuroinflammation, innate immunity, adaptive immunity, gut-brain signaling, neuropsychiatric disorders, neurodevelopmental disorders, neurological disorders, mental illness
MeSH terms
Gastrointestinal Microbiome, Brain-Gut Axis, Animals, Brain, Humans, Immunity, Innate, Adaptive Immunity

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