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Peer-reviewedCC BY 4.0Frontiers in Immunology

Gut microbial metabolites: linking gut–immune–brain crosstalk to mental and neuropsychiatric health

  • Yimao Wu1,2
  • Xiaofei Xie3
  • Weiqi Lyu3
  • Jun-er Xu4
  • Fei Fan5
  • Ruohong Mao6
  • Sihan Pan7
  • Liao Zhang1,5
  • Minggui Fu1
7 affiliations
  1. 1The Affiliated Kangning Hospital of Wenzhou Medical University, Zhejiang Provincial Clinical Research Center for Mental Health
  2. 2Second Clinical Medical College, Guangdong Medical University
  3. 3First Clinical Medical College, Guangdong Medical University
  4. 4Alberta Institute, Wenzhou Medical University
  5. 5School of Mental Health, Wenzhou Medical University
  6. 6School of Chinese Medicine, Wenzhou Medical University
  7. 7Renji College of Wenzhou Medical University
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Abstract

This narrative review adopts the gut-immune-brain axis as the core framework. Literature published 2010-2025 was retrieved from PubMed, Web of Science and ScienceDirect; landmark pre-2010 studies from top journals were also included. Literature was analyzed across five dimensions: metabolite synthesis-transport, intestinal immune regulation, central mediation, disease-pathology links and clinical translation. We elucidate how short-chain fatty acids, tryptophan metabolites and bile acids act as immune messengers to modulate neural homeostasis. Under physiological conditions, they maintain barrier integrity and central immune balance; when dysregulated, they trigger immune disturbance, blood-brain barrier damage and neuroinflammation, promoting Alzheimer’s disease, Parkinson’s disease, major depressive disorder and chronic insomnia. Moving beyond conventional gut-brain-axis reviews focused merely on gut-brain communication, this work highlights immunity as the critical intermediate node and constructs the cascade “gut microbial metabolites-immune regulation-neural homeostasis-disease”. We further summarize biomarker prospects and intervention strategies including dietary fiber, pre-/probiotics and fecal microbiota transplantation. Notably, an ICH-M10-aligned five-stage biomarker validation framework and a gut-brain-immune tri-culture microfluidic model are proposed, offering new directions for mechanistic research and precision therapy for neurological disorders.

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Cite

BibTeXRIS
BibTeX
@article{wu2026microbial,
  title = {{Gut microbial metabolites: linking gut–immune–brain crosstalk to mental and neuropsychiatric health}},
  author = {Yimao Wu and Xiaofei Xie and Weiqi Lyu and Jun-er Xu and Fei Fan and Ruohong Mao and Sihan Pan and Liao Zhang and Minggui Fu},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = nov,
  doi = {10.3389/fimmu.2026.1993237},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1993237/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Gut microbial metabolites: linking gut–immune–brain crosstalk to mental and neuropsychiatric health
AU  - Yimao Wu
AU  - Xiaofei Xie
AU  - Weiqi Lyu
AU  - Jun-er Xu
AU  - Fei Fan
AU  - Ruohong Mao
AU  - Sihan Pan
AU  - Liao Zhang
AU  - Minggui Fu
PY  - 2026
DA  - 2026/11/02
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1993237
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1993237/full
AB  - This narrative review adopts the gut-immune-brain axis as the core framework. Literature published 2010-2025 was retrieved from PubMed, Web of Science and ScienceDirect; landmark pre-2010 studies from top journals were also included. Literature was analyzed across five dimensions: metabolite synthesis-transport, intestinal immune regulation, central mediation, disease-pathology links and clinical translation. We elucidate how short-chain fatty acids, tryptophan metabolites and bile acids act as immune messengers to modulate neural homeostasis. Under physiological conditions, they maintain barrier integrity and central immune balance; when dysregulated, they trigger immune disturbance, blood-brain barrier damage and neuroinflammation, promoting Alzheimer’s disease, Parkinson’s disease, major depressive disorder and chronic insomnia. Moving beyond conventional gut-brain-axis reviews focused merely on gut-brain communication, this work highlights immunity as the critical intermediate node and constructs the cascade “gut microbial metabolites-immune regulation-neural homeostasis-disease”. We further summarize biomarker prospects and intervention strategies including dietary fiber, pre-/probiotics and fecal microbiota transplantation. Notably, an ICH-M10-aligned five-stage biomarker validation framework and a gut-brain-immune tri-culture microfluidic model are proposed, offering new directions for mechanistic research and precision therapy for neurological disorders.
SN  - 1664-3224
ER  -