The gut-brain axis
Open accessAbstract
Preclinical evidence has firmly established bidirectional interactions among the brain, the gut, and the gut microbiome. Candidate signaling molecules and at least three communication channels have been identified. Communication within this system is nonlinear, is bidirectional with multiple feedback loops, and likely involves interactions between different channels. Alterations in gut–brain–microbiome interactions have been identified in rodent models of several digestive, psychiatric, and neurological disorders. While alterations in gut–brain interactions have clearly been established in irritable bowel syndrome, a causative role of the microbiome in irritable bowel syndrome remains to be determined. In the absence of specific microbial targets for more effective therapies, current approaches are limited to dietary interventions and centrally targeted pharmacological and behavioral approaches. A more comprehensive understanding of causative influences within the gut–brain–microbiome system and well-designed randomized controlled trials are needed to translate these exciting preclinical findings into effective therapies.
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The gut-brain axis (GBA) consists of the central nervous system, the autonomic nervous system, the enteric nervous system, the hypothalamic-pituitary-adrenal axis, and the immune system.
“The gut–brain axis (GBA) consists of the CNS, the autonomic nervous system (ANS), the endocrine system (ENS), the hypothalamic-pituitary-adrenal (HPA) axis, and the immune system (34).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [34]
The gut microbiota is closely linked to the central nervous system through the GBA.
“The gut microbiota is closely linked to the CNS through the GBA (34).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [34]
The GBA is a bidirectional communication pathway between the gut and the central nervous system, involving multiple feedback loops and the interaction of different channels.
“The GBA is a bidirectional communication pathway between the gut and the CNS, involving multiple feedback loops and the interaction of different channels (34).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [34]
The gut-brain axis facilitates bidirectional communication between the gut microbiota and the brain, making eubiosis essential for human health.
“GBA facilitates bidirectional communication between the gut microbiota and the brain, making eubiosis essential for human health.”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [40]
The gut-brain axis encompasses interactions between the gut-associated immune system, the enteric nervous system, the vagus nerve, and microbial-derived products, including neurotransmitters, SCFAs, and bile acid derivatives.
“This system encompasses interactions between the gut-associated immune system, the enteric nervous system (ENS), the vagus nerve, and microbial-derived products, including neurotransmitters, SCFAs, and bile acid derivatives [40,41].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [40]
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Młynarska, E., Barszcz, E., Budny, E., Gajewska, A., Kopeć, K., Wasiak, J., Rysz, J., & Franczyk, B. (2025) · Nutrients · doi:10.3390/nu17071135 · Cited by 44 · see citing works
Hong, D., Zhang, C., Wu, W., Lu, X., & Zhang, L. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1133546 · Cited by 38 · see citing works
Study on the comorbid mechanisms of sarcopenia and late-life depression
Wu, J., Tang, J., Huang, D., Wang, Y., Zhou, E., Ru, Q., Xu, G., Chen, L., & Wu, Y. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115538 · Cited by 12 · see citing works
Zheng, R., Huang, S., Feng, P., Liu, S., Jiang, M., Li, H., Zheng, P., Mi, Y., & Li, E. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1557174 · Cited by 6 · see citing works
Dumitru, C. N., Dumitru, A. O., Popa, G. V., Marcu, T., Ursu, M., Nechita, A., & Matei, N. M. (2026) · Dentistry Journal · doi:10.3390/dj14050289 · Cited by 6 · see citing works
CauTrigger: deciphering biological system state transitions by hierarchical causal decomposition
Zhang, C., Cai, D., Aihara, K., & Chen, L. (2026) · Nature Methods · doi:10.1038/s41592-026-03274-9
- Authors
- Mayer, E. A., Nance, K., & Chen, S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Mayer, Emeran A.
- Venue
- Annual Review of Medicine
- Publisher
- Annual Reviews
- Published
- 2022-01-27
- Volume
- 73
- Issue
- 1
- Pages
- 439-453
- ISSN
- 0066-4219 (ISSN-L)
- 1545-326X
- OpenAlex
- W3205708972
- Cited by
- 813
- References
- 80
- Citations by year
- 2026: 191 · 2025: 248 · 2024: 241 · 2023: 106 · 2022: 27
- FWCI
- 17.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK048351, P30DK041301)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut-brain axis, gut microbiota, two-way communication, signaling molecules, irritable bowel syndrome, mental illness, neurological disorders, dietary intervention, microbiome-targeted therapy, rodent models
- MeSH terms
- Gastrointestinal Microbiome, Brain-Gut Axis, Brain, Humans, Irritable Bowel Syndrome, Microbiota
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