Regulation of prefrontal cortex myelination by the microbiota
Open accessAbstract
The prefrontal cortex (PFC) is a key region implicated in a range of neuropsychiatric disorders such as depression, schizophrenia and autism. In parallel, the role of the gut microbiota in contributing to these disorders is emerging. Germ-free (GF) animals, microbiota-deficient throughout life, have been instrumental in elucidating the role of the microbiota in many aspects of physiology, especially the role of the microbiota in anxiety-related behaviours, impaired social cognition and stress responsivity. Here we aim to further elucidate the mechanisms of the microbial influence by investigating changes in the homeostatic regulation of neuronal transcription of GF mice within the PFC using a genome-wide transcriptome profiling approach. Our results reveal a marked, concerted upregulation of genes linked to myelination and myelin plasticity. This coincided with upregulation of neural activity-induced pathways, potentially driving myelin plasticity. Subsequent investigation at the ultrastructural level demonstrated the presence of hypermyelinated axons within the PFC of GF mice. Notably, these changes in myelin and activity-related gene expression could be reversed by colonization with a conventional microbiota following weaning. In summary, we believe we demonstrate for the first time that the microbiome is necessary for appropriate and dynamic regulation of myelin-related genes with clear implications for cortical myelination at an ultrastructural level. The microbiota is therefore a potential therapeutic target for psychiatric disorders involving dynamic myelination in the PFC.
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The gut microbiome modulates oligodendrocyte maturation and myelin production.
“Notably, the gut microbiome has been shown to modulate oligodendrocyte maturation and myelin production.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [265]
Perturbations in the gut microbiome, including germ-free conditions and antibiotic treatment, trigger excessive myelination in the prefrontal cortex by inducing oligodendrocyte maturation and upregulating myelin-related genes.
“Perturbations in gut microbiome, including GF conditions and antibiotic treatment, have been shown to trigger excessive myelination in the prefrontal cortex by inducing oligodendrocyte maturation and upregulating myelin-related genes.62,265”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [265]
Alterations in GF mice are ameliorated by colonization with a conventional microbiota following weaning.
“Importantly, these alterations in GF mice were ameliorated by colonization with a conventional microbiota following weaning.265”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [265]
Gut microbes not only regulate gene expression in the mouse brain, but also affect alternative splicing, and can regulate the production of specific isoforms of genes that have been implicated in ASD.
“These findings suggest that gut microbes not only regulate gene expression in the mouse brain (Hoban et al., 2016; Neufeld et al., 2011; Stilling et al., 2015), but also affect alternative splicing (Stilling et al., 2018), and can regulate the production of specific isoforms of genes that have been implicated in ASD.”
From Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019) · cites this paper as Hoban et al., 2016
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Self-citation
- Authors
- Hoban, A. E., Stilling, R. M., Ryan, F. J., Shanahan, F., Dinan, T. G., Claesson, M. J., Clarke, G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Corresponding author
- Cryan, J F
- Venue
- Translational Psychiatry
- Published
- 2016-04-05
- Volume
- 6
- Issue
- 4
- Pages
- e774-e774
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4872400
- OpenAlex
- W2313364663
- Cited by
- 635
- References
- 62
- Citations by year
- 2026: 37 · 2025: 56 · 2024: 72 · 2023: 65 · 2022: 65 · 2021: 75 · 2020: 63 · 2019: 60 · 2018: 65 · 2017: 50 · 2016: 27
- FWCI
- 35.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (acceptedVersion)
- Cork Open Research Archive (University College Cork, Ireland) (submittedVersion, cc-by)
- Funders
- AstraZeneca
- Mead Johnson Nutrition
- National Alliance for Research on Schizophrenia and Depression (20771)
- Enterprise Ireland
- Science Foundation Ireland (20771, 12/RC/2273, 12/RC/)
- University of Galway
- University College Cork
- Trinity College Dublin
- Irish Research Council
- Servier
- H. Lundbeck A/S
- APC Microbiome Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- gut microbiota, prefrontal cortex, myelination, myelin plasticity, germ-free mice, microbiota colonization, neuronal gene expression, neuronal activity, mental illness, depression, schizophrenia, autism spectrum disorder
- MeSH terms
- Animals, Myelin Sheath, Synaptic Transmission, Blotting, Western, Up-Regulation, Prefrontal Cortex, Gene Expression Profiling, Microscopy, Electron, Transmission, Mice, Transcriptome, Real-Time Polymerase Chain Reaction, Microbiota
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