Role of intestinal microbiome in depression

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Abstract

Depression has become one of the most significant concerns in neuropsychiatry and neuropharmacology. This is supported by recent concepts that emphasize the variability of mechanisms underlying depression. The pathogenesis of depression involves multiple factors, including changes in hypothalamic–pituitary–adrenal axis regulation, impaired homeostasis with destabilized monoamine levels, and reduced neuroplasticity with cytokine expression and microglia activation. Recent research into the gut-brain axis has significantly improved our understanding of the mechanisms behind depression. The interactions between the intestinal microbiome and the central nervous system are thought to have numerous manifestations, including those that can serve as predictors of depression. These characteristics include neurotransmitter signaling, cofactor-mediated stimulation, and increased synthesis of neurotransmitters required for mental health stabilization. However, there is currently no consensus on the nature of these interactions. Therefore, it is relevant to summarize data on the interactions between the intestinal microbiota and the central nervous system in order to improve the treatment of depressive disorders. This review summarizes research papers from PubMed, eLIBRARY.RU, MEDLINE, PMC, PMID, PMCID, and Google Scholar databases published between 2000 and July 30, 2025, examining the relationship between depressive disorders and anxiety and changes in microbiome composition. The review included case-control studies assessing the characteristics of intestinal microbiota (microbiome) in humans and experimental animals (excluding virome, Archaea, and eukaryotic parasites) in depression and anxiety. Commensal and pathogenic strains were found to contribute to persistent changes in brain functioning. From a pharmacological perspective, data on changes in microorganisms associated with depression and anxiety were summarized. Furthermore, drugs capable of changing the microbiological balance and, thus, indirectly promoting these disorders were identified.

About the authors

Yuri A. Sergeev

Stavropol State Medical University

Author for correspondence.
Email: serg_yuriy@mail.ru
ORCID iD: 0000-0002-6183-2586
SPIN-code: 3007-8098

MD, Cand. Sci. (Medicine)

Russian Federation, Stavropol

Eduard V. Beyer

Stavropol State Medical University

Email: karokris@mail.ru
ORCID iD: 0000-0003-3248-6212
SPIN-code: 3411-1334

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Stavropol

Igor A. Bazikov

Stavropol State Medical University

Email: bazikov@list.ru
ORCID iD: 0000-0001-9207-6552
SPIN-code: 7585-8596

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Stavropol

Tatyana V. Taran

Stavropol State Medical University

Email: mikra-2018@mail.ru
ORCID iD: 0000-0002-8070-0706
SPIN-code: 9158-3750

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Stavropol

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