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Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis
Abstract
To date, there is rapidly increasing evidence for host-microbe interaction at virtually all levels of complexity, ranging from direct cell-to-cell communication to extensive systemic signalling, and involving various organs and organ systems, including the central nervous system. As such, the discovery that differential microbial composition is associated with alterations in behaviour and cognition has significantly contributed to establishing the microbiota-gut-brain axis as an extension of the well-accepted gut-brain axis concept. Many efforts have been focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome to neurodevelopmental disorders such as autism. There is also a growing appreciation of the role of epigenetic mechanisms in shaping brain and behaviour. However, the role of epigenetics in informing host-microbe interactions has received little attention to date. This is despite the fact that there are many plausible routes of interaction between epigenetic mechanisms and the host-microbiota dialogue. From this new perspective we put forward novel, yet testable, hypotheses. Firstly, we suggest that gut-microbial products can affect chromatin plasticity within their host's brain that in turn leads to changes in neuronal transcription and eventually alters host behaviour. Secondly, we argue that the microbiota is an important mediator of gene-environment interactions. Finally, we reason that the microbiota itself may be viewed as an epigenetic entity. In conclusion, the fields of (neuro)epigenetics and microbiology are converging at many levels and more interdisciplinary studies are necessary to unravel the full range of this interaction.
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“Preclinical evidence suggests that GM-mediated mechanisms are likely involved in modulating brain processes, including brain biochemistry, response to stress, pain interpretation, feeding, emotional behaviors, and cognition (57–64).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [57]
In the citing paper
“Studies have since shown that gut bacteria play a vital role in regulating important aspects of brain development and function, along with other host physiology [5, 7].”
From Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review (2020) · cites this paper as [7]
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“Lastly, butyrate and, to a lesser extent, other SCFAs can also act as a potent inhibitor of histone deacetylases (HDACs) (357).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [357]
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Metadata
- Authors
- Stilling, R. M., Dinan, T. G., & Cryan, J. F.
- Affiliations
- APC Microbiome Institute (IE)
- University College Cork (IE)
- Corresponding author
- Cryan, J. F.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2013-12-27
- Volume
- 13
- Issue
- 1
- Pages
- 69-86
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W1490861410
- Cited by
- 637
- References
- 191
- Citations by year
- 2026: 36 · 2025: 44 · 2024: 46 · 2023: 47 · 2022: 65 · 2021: 59 · 2020: 68 · 2019: 45 · 2018: 50 · 2017: 55 · 2016: 50 · 2015: 47 · 2014: 25
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- microbiota-gut-brain axis, gut-brain axis, epigenetics, host-microbe interactions, chromatin plasticity, gene-environment interaction, depression, anxiety, irritable bowel syndrome, autism spectrum disorder, neurodevelopmental disorders, microbial metabolites, behavior
- MeSH terms
- Animals, Brain, Genes, Bacterial, Humans, Intestines, Stress, Psychological, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Host-Pathogen Interactions, Gene-Environment Interaction, Microbiota
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