Gut-brain axis serotonergic responses to acute stress exposure are microbiome-dependent
Abstract
BACKGROUND: Understanding the mechanisms underpinning the response to acute stress is critical for determining how this can be modulated in both health and disease and across sexes. Stress can markedly alter the microbiome and gut-brain axis signaling with the serotonergic system being particularly sensitive to acute stress. As the impact of acute stress on regional serotonergic dynamics in the gut-brain axis and the contribution of the microbiome to this are poorly appreciated, we used microbiota-deficient mice to assess whether the serotonergic response to acute stress exposure is microbiome dependent. METHODS: Adult male and female conventional, germ-free, and colonized germ-free mice underwent a single acute stressor and samples were harvested immediately or 45 minutes following stress. Serotonin and related metabolites and serotonergic gene expression were determined. KEY RESULTS: Our data clearly show the microbiota influenced gastrointestinal serotonergic response to acute stress in a sex- and region-dependent manner. Male-specific poststress increases in colonic serotonin were absent in germ-free mice but normalized following colonization. mRNA serotonergic gene expression was differentially expressed in colon and ileum of germ-free mice on a sex-dependent basis. Within the frontal cortex, absence of the microbiome altered basal serotonin, its main metabolite 5-hydroxyindoleacetic acid, and prevented stress-induced increases in serotonin turnover. CONCLUSIONS AND INFERENCES: The gut microbiome influences the set points of the brain and gastrointestinal serotonergic systems and affected their response to acute stress in a sex- and region-dependent manner.
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Several metabolomic studies show alterations in the dopamine and serotonin systems in germ-free animals.
“Several metabolomic studies show alterations in the dopamine and serotonin systems (124, 189, 350, 378–380).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [379]
These changes include increased hippocampal dopamine D1 receptor mRNA levels, decreased dopamine D1 receptor in the striatum and nucleus accumbens, increased serotonin in the blood and hippocampus, and decreased serotonin receptor expression.
“These changes include increased hippocampal dopamine D1 receptor mRNA levels and decreased dopamine D1 receptor in the striatum and nucleus accumbens, as well as increased serotonin in the blood and hippocampus, with decreased serotonin receptor expression, respectively.”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [379]
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Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
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- Authors
- Lyte, J. M., Gheorghe, C. E., Goodson, M. S., Kelley‐Loughnane, N., Dinan, T. G., Cryan, J. F., & Clarke, G.
- Affiliations
- University College Cork (IE)
- United States Air Force Research Laboratory (US)
- Corresponding author
- Clarke, Gerard
- ORCID
- Venue
- Neurogastroenterology & Motility
- Publisher
- Wiley
- Published
- 2020-05-11
- Volume
- 32
- Issue
- 11
- Pages
- e13881-e13881
- ISSN
- 1350-1925 (ISSN-L)
- 1365-2982
- OpenAlex
- W3021933741
- Cited by
- 77
- References
- 47
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 15 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 1
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Neurogastroenterology & Motility (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science Foundation Ireland (SFI/12/RC/2273)
- Air Force Office of Scientific Research (FA9550‐17‐1‐0016)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- gut-brain axis, acute stress, gut microbiota, serotonergic system, serotonin, 5-hydroxyindoleacetic acid, germ-free mice, microbiota colonization, sex differences, frontal cortex, serotonin turnover
- MeSH terms
- Gastrointestinal Microbiome, Animals, Colon, Corticosterone, Female, Frontal Lobe, Germ-Free Life, Hydroxyindoleacetic Acid, Ileum, Male, Restraint, Physical, RNA, Messenger, Serotonin, Sex Factors, Stress, Psychological, Tryptophan Hydroxylase, Gene Expression, Indoleamine-Pyrrole 2,3,-Dioxygenase, Mice
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