Microbial regulation of hippocampal miRNA expression: implications for transcription of kynurenine pathway enzymes
Abstract
Increasing evidence points to a functional role of the enteric microbiota in brain development, function and behaviour including the regulation of transcriptional activity in the hippocampus. Changes in CNS miRNA expression may reflect the colonisation status of the gut. Given the pivotal impact of miRNAs on gene expression, our study was based on the hypothesis that gene expression would also be altered in the germ-free state in the hippocampus. We measured miRNAs in the hippocampus of Germ free (GF), conventional (C) and Germ free colonised (exGF) Swiss Webster mice. miRNAs were selected for follow up based on significant differences in expression between groups according to sex and colonisation status. The expression of miR-294-5p was increased in male germ free animals and was normalised following colonisation. Targets of the differentially expressed miRNAs were over-represented in the kynurenine pathway. We show that the microbiota modulates the expression of miRNAs associated with kynurenine pathway metabolism and, demonstrate that the gut microbiota regulates the expression of kynurenine pathway genes in the hippocampus. We also show a sex-specific role for the microbiota in the regulation of miR-294-5p expression in the hippocampus. The gut microbiota plays an important role in modulating small RNAs that influence hippocampal gene expression, a process critical to hippocampal development.
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Evidence from studies in germ-free rodents shows microbial regulation of miRNA expression in brain regions of importance for neuropsychiatry such as the amygdala, prefrontal cortex, and hippocampus.
“evidence emerge from studies in germ-free rodents of microbial regulation of miRNA expression in brain regions of importance for neuropsychiatry such as the amygdala, prefrontal cortex, and hippocampus (Chen et al., 2017;Hoban et al., 2017;Moloney et al., 2017).”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Moloney et al., 2017
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- Authors
- Moloney, G. M., O’Leary, O. F., Salvo-Romero, E., Desbonnet, L., Shanahan, F., Dinan, T. G., Clarke, G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Corresponding author
- Clarke, Gerard
- ORCID
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 334
- Pages
- 50-54
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2736438146
- Cited by
- 68
- References
- 24
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 11 · 2023: 6 · 2022: 8 · 2021: 9 · 2020: 5 · 2019: 10 · 2018: 4
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- COST program (BM1106)
- European Society of Neurogastroenterology and Motility
- Short Term Scientific Mission
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- gut microbiota, hippocampus, microRNA expression, kynurenine pathway, germ-free mice, sex differences, microbiota-gut-brain axis, hippocampal gene expression, Swiss Webster mice
- MeSH terms
- Gastrointestinal Microbiome, Animals, Female, Gene Expression Regulation, Hippocampus, Kynurenine, Male, Sex Characteristics, MicroRNAs, Mice, Microbiota
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