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Microbiota-derived metabolites as drivers of gut–brain communication
Open accessAbstract
Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The gut microbes transform and metabolize dietary- and host-derived molecules generating a diverse group of metabolites with local and systemic effects. The bi-directional communication between brain and the microbes residing in the gut, the so-called gut–brain axis, consists of a network of immunological, neuronal, and endocrine signaling pathways. Although the full variety of mechanisms of the gut–brain crosstalk is yet to be established, the existing data demonstrates that a single metabolite or its derivatives are likely among the key inductors within the gut–brain axis communication. However, more research is needed to understand the molecular mechanisms underlying how gut microbiota associated metabolites alter brain functions, and to examine if different interventional approaches targeting the gut microbiota could be used in prevention and treatment of neurological disorders, as reviewed herein.Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty acid; 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic acid; ZO Zonula occludens proteins
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“Evidence has unveiled the bidirectional communication between the gut microbiome and the central nervous system, referred to as the “microbiota–gut–brain axis”.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [30]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
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Wang, X., Wen, X., Yuan, S., & Zhang, J. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106499 · Cited by 47
Jaric, I., Voelkl, B., Clerc, M., Schmid, M. W., Novak, J., Rosso, M., Rufener, R., von Kortzfleisch, V. T., Richter, S. H., Buettner, M., et al. (2022) · PLoS Biology · doi:10.1371/journal.pbio.3001837 · Cited by 32
Zhang, X., Wang, H., Kilpatrick, L. A., Dong, T. S., Gee, G. C., Labus, J. S., Osadchiy, V., Beltran-Sanchez, H., Wang, M. C., Vaughan, A., et al. (2023) · Nature Mental Health · doi:10.1038/s44220-023-00134-9 · Cited by 20
Psychobiotics in mental health: insights from human clinical trials via the gut-brain axis
Sisubalan, N., Kesika, P., Sivamaruthi, B. S., & Chaiyasut, C. (2026) · Frontiers in microbiology · doi:10.3389/fmicb.2026.1804560 · Cited by 4
“Among these interactions, the relationship between the gut and the brain is particularly prominent and is mediated through interconnected signaling pathways collectively known as the gut-brain axis (Ahmed et al., 2022).”
Metadata
- Authors
- Ahmed, H., Leyrolle, Q., Koistinen, V., Kärkkäinen, O., Layé, S., Delzenne, N., & Hanhineva, K.
- Affiliations
- University of Turku (FI)
- UCLouvain (BE)
- University of Eastern Finland (FI)
- Université de Bordeaux (FR)
- Corresponding author
- Ahmed, Hany
- ORCID
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2022-07-28
- Volume
- 14
- Issue
- 1
- Pages
- 2102878-2102878
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC9341364
- OpenAlex
- W4288436705
- Cited by
- 462
- References
- 208
- Citations by year
- 2026: 135 · 2025: 161 · 2024: 110 · 2023: 48 · 2022: 7
- FWCI
- 26.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Gut Microbes (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
- UTUPub (University of Turku) (submittedVersion)
- HAL (submittedVersion, cc-by)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Funders
- Academy of Finland ((Grant no 321716))
- Marie Sklodowska-Curie ((Grant no 754412.)
- Région Nouvelle Aquitaine ExoMarquAge ((135059720-13062120))
- The Foundation for Medical Research
- 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, gut microbiota metabolites, gut-brain axis, neurodevelopmental disorders, neurodegenerative diseases, neuropsychiatric disorders, short-chain fatty acids, trimethylamine N-oxide, bile acids, aryl hydrocarbon receptor, autism spectrum disorder, maternal immune activation, blood-brain barrier, brain-derived neurotrophic factor, germ-free mice
- MeSH terms
- Autism Spectrum Disorder, Gastrointestinal Microbiome, Brain, Fatty Acids, Volatile, Humans, Amyloid beta-Peptides
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