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The Role of the Microbiome-Brain-Gut Axis in the Pathogenesis of Depressive Disorder
Open accessAbstract
The role of gut microbiota and its association with the central nervous system via the microbiome-brain-gut axis has been widely discussed in the literature. The aim of this review is to investigate the impact of gut microbiota on the development of depression and underlying molecular mechanisms. There are two possible pathways in which this interaction might occur. The first one suggests that depressive disorder could lead to dysbiosis and one of the causes may be the influence on the hypothalamic-pituitary-adrenal (HPA) axis. The second one considers if changes in the composition of gut microbiota might cause depressive disorder. The mechanisms that could be responsible for this interaction include the secretion of neurotransmitters, gut peptides and the activation of the immune system. However, current knowledge on this topic does not allow for us to state an unambiguous conclusion, and future studies that take into consideration more precise stress-measurement methods are needed to further explore direct mechanisms of the interaction between gut microbiota and mental health.
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![Figure 1 Hypothetic communication pathway between the brain and the gut microbiota in the depressive state. A depressed state triggers alterations in the microbiota via the hypothalamic-pituitary-adrenal axis and the immune system. This might lead to intestinal symptoms which can be further exacerbated by stress [10].](/paper-figures/b4da26a38de3487694fcbcc6867c831a/the-role-of-the-microbiome-brain-gut-axis-in-the-pathogenesis-of-depressive-figure-1.jpg)

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“Examples of these metabolic products include SCFAs, which are produced by Lactobacillus, Bifidobacterium, and Prevotella [93].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [93]
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THE ROLE OF GUT MICROBIOTA IN THE PATHOGENESIS OF DEPRESSION - CURRENT STATE OF KNOWLEDGE
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Efejene, I. O., Ben‐Azu, B., Eduviere, A. T., Esuku, D. T., Chijioke, B. S., Chidebe, E. O., Moses, A. S., Iwhiwhu, P., Omogbiya, I. A., Ajayi, A. M., et al. (2026) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.70095
Intestinal Flora and Depression: Interaction Mechanisms and Therapeutic Prospects
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Metadata
- Authors
- Młynarska, E., Gadzinowska, J., Tokarek, J., Forycka, J., Szuman, A., Franczyk, B., & Rysz, J.
- Affiliations
- Medical University of Lodz (PL)
- Corresponding author
- Młynarska, Ewelina
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2022-05-04
- Volume
- 14
- Issue
- 9
- Pages
- 1921
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC9105444
- OpenAlex
- W4225384750
- Cited by
- 109
- References
- 123
- Citations by year
- 2026: 22 · 2025: 35 · 2024: 26 · 2023: 26
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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, depression, dysbiosis, hypothalamic-pituitary-adrenal axis, neurotransmitters, gut peptides, immune activation, stress, mental health
- MeSH terms
- Gastrointestinal Microbiome, Brain-Gut Axis, Brain, Depressive Disorder, Humans, Pituitary-Adrenal System, Dysbiosis
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