Current perspectives on gut microbiome dysbiosis and depression
Open accessAbstract
The human gut microbiome partakes in a bidirectional communication pathway with the central nervous system (CNS), named the microbiota-gut-brain axis. The microbiota-gut-brain axis is believed to modulate various central processes through the vagus nerve as well as production of microbial metabolites and immune mediators which trigger changes in neurotransmission, neuroinflammation, and behavior. Little is understood about the utilization of microbiome manipulation to treat disease. Though studies exploring the role of the microbiome in various disease processes have shown promise, mechanisms remain unclear and evidence-based treatments for most illnesses have not yet been developed. The animal studies reviewed here offer an excellent array of basic science research that continues to clarify mechanisms by which the microbiome may affect mental health. More evidence is needed, particularly as it relates to translating this work to human subjects. The studies presented in this paper largely demonstrate encouraging results in the treatment of depression. Limitations include small sample sizes and heterogeneous methodology. The exact mechanism by which the gut microbiota causes or alters neuropsychiatric disease states is not fully understood. In this review, we focus on recent studies investigating the relationship between gut microbiome dysbiosis and the pathogenesis of depression. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
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The microbiota-gut-brain axis is believed to regulate various central processes through microbial metabolites.
“The participation of gut microbiome in bidirectional communication pathway with the central nervous system (CNS) was named the microbiota-gut-brain axis, which is believed to regulate various central processes through microbial metabolites [98].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [98]
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The role of gut microbiota in depression: an analysis of the gut-brain axis
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“This results in an increase in serotonin level and a reduction in depressive symptoms (Capuco et al., 2020).”
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BackgroundImpact of nonalcoholic fatty liver disease-related metabolic state on depression
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Gut Microbiota – A Potential Contributor in the Pathogenesis of Bipolar Disorder
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Fecal Microbiota Analysis in Cats with Intestinal Dysbiosis of Varying Severity
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The Gut Microbiota and Chronic Pain
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“Similar observations were made by authors reviewing the relationship between the gut microbiome and its interaction with depression [108].”
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“further elucidate the relationship between IBD, childhood trauma, depression and suicide risk (Capuco et al., 2020; Moulton et al., 2019).”
BackgroundThe Effect of Gut Microbiome, Neurotransmitters, and Digital Insights in Autism
Bamicha, V., Pergantis, P., & Drigas, A. S. (2024) · Applied Microbiology · doi:10.3390/applmicrobiol4040114 · Cited by 22 · see citing works
“Three routes of communication—neuronal, endocrine, and immunoregulatory mechanisms—connect the gut microbiota to the brain [38,56].”
Microbiome, Therapeutics Application and Epigenetics: Conclusion and Future Prospective
Chauhan, N. S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819265-8.00025-5 · Cited by 22 · see citing works
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“Recent studies suggest the microbiota–gut–brain axis as a bi-directional communication pathway in pathogenesis of various mental complications [60].”
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The Gut-Brain Axis and Its Role in Depression
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Role of sulfidogenic members of the gut microbiota in human disease
Pimenta, A. I., Bernardino, R. M., & Pereira, I. A. C. (2024) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/bs.ampbs.2024.04.003 · Cited by 18 · see citing works
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Modification of post-traumatic epilepsy by fecal microbiota transfer
Medel‐Matus, J., Simpson, C. A., Ahdoot, A., Shin, D. H., Sankar, R., Jacobs, J. P., & Mazarati, A. M. (2022) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2022.108860 · Cited by 18 · see citing works
Assessing and removing the effect of unwanted technical variations in microbiome data
Fachrul, M., Méric, G., Inouye, M., Pamp, S. J., & Salim, A. (2022) · Scientific Reports · doi:10.1038/s41598-022-26141-x · Cited by 17 · see citing works
The Role of the Microbiome in First Episode of Psychosis
Nuncio-Mora, L., Lanzagorta, N., Nicolini, H., Sarmiento, E., Ortiz, G., Sosa, F., & Mendoza, A. D. G. (2023) · Biomedicines · doi:10.3390/biomedicines11061770 · Cited by 18 · see citing works
“Thus, gain, loss, or changes in the abundance of different taxa of bacteria represent an imbalance that is known as “gut dysbiosis”, which can occur due to disorders related and unrelated to the gastrointestinal tract, use of antibiotics, high-fat and high-sugar diets, and exposure to pesticides and heavy metals [10,1…”
BackgroundKiran, N. S., Yashaswini, C., & Chatterjee, A. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122311 · Cited by 19 · see citing works
Zhong, K. X., Cho, A., Deeg, C., Chan, A. M., & Suttle, C. A. (2021) · Microbiome · doi:10.1186/s40168-021-01180-0 · Cited by 17 · see citing works
Gerace, E., Baldi, S., Salimova, M., Gloria, L. D., Curini, L., Cimino, V., Nannini, G., Russo, E., Pallecchi, M., Ramazzotti, M., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106627 · Cited by 16 · see citing works
“Microbiota dysfunction has been associated with several diseases and a significant body of evidence has identified microbial dysbiosis as a contributor to cognitive and neuropsychiatric disorders.(1,2) Recent findings elucidated the importance of the gut microbiota (GM) and its metabolites, especially short chain fatt…”
BackgroundImportance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis
Costa, C. F. F. A., Ferreira‐Gomes, J., Barbosa, F., Sampaio‐Maia, B., & Burnet, P. W. J. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1386866 · Cited by 16 · see citing works
Petrak, F., Herpertz, S., Hirsch, J., Röhrig, B., Donati-Hirsch, I., Juckel, G., Meier, J. J., & Gatermann, S. G. (2022) · BMC Microbiology · doi:10.1186/s12866-022-02575-1 · Cited by 16 · see citing works
“In contrast, in rats put under chronic stress, lower alpha diversity has been found and Bacteroidetes were increased [24].”
BackgroundMicrobes, oxytocin and stress: Converging players regulating eating behavior
Cuesta‐Marti, C., Uhlig, F., Muguerza, B., Hyland, N. P., Clarke, G. A., & Schellekens, H. (2023) · Journal of Neuroendocrinology · doi:10.1111/jne.13243 · Cited by 15 · see citing works
“148 The composition of the microbiome modulates the response to acute 149,150 and chronic stress.”
Szala‐Rycaj, J., Szewczyk, A., Zagaja, M. P., Kaczmarczyk‐Ziemba, A., Maj, M., & Andres‐Mach, M. (2023) · Nutrients · doi:10.3390/nu15092041 · Cited by 15 · see citing works
“Recent clinical studies have shown that intestinal dysbiosis is correlated with the occurrence of depression [9,10].”
BackgroundOuyang, P., Kang, D.-L., You, W., Shen, X., Mo, X., & Liu, Y. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1303002 · Cited by 13 · see citing works
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The Bidirectional Relationship Between the Gut Microbiome and Mental Health: A Comprehensive Review
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The Importance of the Microbiota in Shaping Women’s Health—The Current State of Knowledge
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Bibliometric Visualization Analysis of Microbiome-Gut-Brain Axis from 2004 to 2020
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Anxiolytic effects of Enterococcus faecalis 2001 on a mouse model of colitis
Takahashi, K., Tsuji, M., Nakagawasai, O., Miyagawa, K., Kurokawa, K., Mochida-Saito, A., Iwasa, M., Iwasa, H., Suzuki, S., Takeda, H., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-62309-3 · Cited by 11 · see citing works
Nutrition and the gut-brain axis in neonatal brain injury and development
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Engineering Organoids for in vitro Modeling of Phenylketonuria
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“…of the gut microbiota as a risk factor for the development of emotion dysregulation in infants [33], associations with affective disorders [34], and aggression in other species (e.g., dogs, rodents, and Drosophila [35–37]), there are no empirical studies in humans investigating this topic…”
BackgroundBahmani, M., Mehrtabar, S., Jafarizadeh, A., Zoghi, S., Heravi, F. S., Abbasi, A., Sanaie, S., Rahnemayan, S., & Leylabadlo, H. E. (2024) · Current Pharmaceutical Biotechnology · doi:10.2174/0113892010281892240116081031 · Cited by 10 · see citing works
Using lifestyle interventions and the gut microbiota to improve PTSD symptoms
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“Patients with depression commonly experience gastrointestinal (GI) symptoms such as constipation, nausea, bloating, abdominal pain, and vomiting [31].”
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“Causes of disorders in the human intestinal ecosystem include factors such as obesity, inadequate diet (high-fat, processed), use of antibiotics, exposure to heavy metals and pesticides, type of feeding during infancy (breast or milk-replacement mixture), as well as a mode of delivery via cesarean section [13,17].”
BackgroundLoo, K.-Y., Thong, J. Y. H., Tan, L. T., Letchumanan, V., Chan, K., Lee, L., & Law, J. W. (2024) · Progress In Microbes & Molecular Biology · doi:10.36877/pmmb.a0000457 · Cited by 8 · see citing works
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“…posits that a disruption in the normal, healthy balance of the gut microbio-ta—a state known as dysbiosis—can lead to dysfunction along the MGB axis, thereby increasing an individual's vulnerability to developing MDD (Foster and McVey Neufeld 2013; Capuco et al. 2020; Modesto Lowe et al. 2023).”
Campisi, S. C., Zasowski, C., Shah, S., Bradley-Ridout, G., Madigan, S. L., Szatmári, P., & Korczak, D. J. (2021) · Advances in Nutrition · doi:10.1093/advances/nmab088 · Cited by 9 · see citing works
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“Furthermore, dysbiosis of the microbiome is associated with comorbid psychiatric disorders such as anxiety, depression, and stress responsivity indicating a potential for the microbiome to contribute to addiction liability (Capuco et al., 2020; Madison and Kiecolt-Glaser, 2019).”
BackgroundKetamine induced gut microbiota dysbiosis and barrier and hippocampal dysfunction in rats
Xie, L., Zhuang, Z., Guo, B., Huang, Y., Shi, X., Huang, Z., Xu, Z., Chen, Y., Cao, Y., Zheng, Y., et al. (2024) · iScience · doi:10.1016/j.isci.2024.111089 · Cited by 6 · see citing works
- Authors
- Capuco, A., Urits, I., Hasoon, J., Chun, R., Gerald, B., Wang, J. K., Kassem, H., Ngo, A. L., Abd-Elsayed, A., Simopoulos, T., Kaye, A. D., & Viswanath, O.
- Affiliations
- Georgetown University (US)
- Beth Israel Deaconess Medical Center (US)
- University of Arizona College of Medicine- Phoenix (US)
- Harvard University (US)
- Mount Sinai Medical Center (US)
- University of Wisconsin–Madison (US)
- Louisiana State University Health Sciences Center Shreveport (US)
- Creighton University (US)
- Corresponding author
- Urits, Ivan
- ORCID
- Venue
- Advances in Therapy
- Published
- 2020-03-04
- Volume
- 37
- Issue
- 4
- Pages
- 1328-1346
- ISSN
- 0741-238X (ISSN-L)
- 1865-8652
- PMC
- PMC7140737
- OpenAlex
- W3010636850
- Cited by
- 216
- References
- 49
- Citations by year
- 2026: 18 · 2025: 29 · 2024: 33 · 2023: 59 · 2022: 41 · 2021: 27 · 2020: 7 · 2017: 1
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Advances in Therapy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- 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 dysbiosis, depression, microbiota-gut-brain axis, vagus nerve, microbial metabolites, neuroinflammation, neurotransmission, neuropsychiatric disorders, animal models of depression, microbiota-based therapy
- MeSH terms
- Gastrointestinal Microbiome, Animals, Brain, Central Nervous System, Depression, Humans, Dysbiosis
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