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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 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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“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
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
Gerace, E., Baldi, S., Salimova, M., Gloria, L. D., Curini, L., Cimino, V., Nannini, G., Russo, E., Pallecchi, M., Ramazzotti, M., et al. (2022) · iScience · doi:10.1016/j.isci.2023.106627 · Cited by 17
“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 19
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
“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 17
“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 16
“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
Breivik, T. J., Gjermo, P. E., Gundersen, Y., Opstad, P. K., Murison, R. C. C., Hugoson, A., von Hörsten, S., & Fristad, I. (2024) · Periodontology 2000 · doi:10.1111/prd.12610 · Cited by 15
The Bidirectional Relationship Between the Gut Microbiome and Mental Health: A Comprehensive Review
Rathore, K. B., Shukla, N., Naik, S., Sambhav, D. K., Dange, K. J., Bhuyan, D., & Haq, Q. M. I. (2025) · Cureus · doi:10.7759/cureus.80810 · Cited by 20
Gao, K., Chen, C.-L., Ke, X.-Q., Yu, Y.-X., Chen, S., Liu, G.-C., Wang, H.-F., & Li, Y.-J. (2022) · Beneficial Microbes · doi:10.3920/bm2022.0052 · Cited by 16
Budin, A. J., Brown, W. A., MacCormick, A. D., Caterson, I. D., & Sumithran, P. (2025) · Obesity Reviews · doi:10.1111/obr.13927 · Cited by 18
The Importance of the Microbiota in Shaping Women’s Health—The Current State of Knowledge
Krupa-Kotara, K. H., Helisz, P., Gwioździk, W., & Grajek, M. K. (2022) · Applied Microbiology · doi:10.3390/applmicrobiol3010002 · Cited by 15
Bibliometric Visualization Analysis of Microbiome-Gut-Brain Axis from 2004 to 2020
Wang, H., Long, T., You, J., Li, P., & Xu, Q. (2022) · Medical Science Monitor · doi:10.12659/msm.936037 · Cited by 13
Natale, N. R., Kent, M., Fox, N. S., Vavra, D. T., & Lambert, K. G. (2021) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2021.10.004 · Cited by 12
Boschetti, E., Neri, I., Follo, M. Y., GIORGIO, R. D., Cocco, L., Manzoli, L., & Ratti, S. (2022) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557522666220622111501 · Cited by 13
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
Nutrition and the gut-brain axis in neonatal brain injury and development
Perez, K., Strobel, K. M., Hendrixson, D. T., Brandon, O. C., Hair, A. B., Workneh, R., Abayneh, M., Nangia, S., Hoban, R. A., Kolnik, S. E., et al. (2024) · Seminars in Perinatology · doi:10.1016/j.semperi.2024.151927 · Cited by 11
Engineering Organoids for in vitro Modeling of Phenylketonuria
Borges, A. C., Broersen, K., Leandro, P., & Fernandes, T. G. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.787242 · Cited by 14
Jakobi, B., Cimetti, C., Mulder, D., Vlaming, P., Franke, B., Hoogman, M., & Vásquez, A. A. (2024) · Nutrients · doi:10.3390/nu16142174 · Cited by 10
“…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
Using lifestyle interventions and the gut microbiota to improve PTSD symptoms
Sugden, S. G., & Merlo, G. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1488841 · Cited by 11
Fatimi, H. E., El‐Mansoury, B., Tinakoua, A., Ndayambaje, M., Zaid, Y., Khalki, H., & Khalki, L. (2025) · Pharmacological Reports · doi:10.1007/s43440-025-00759-w · Cited by 10
“Patients with depression commonly experience gastrointestinal (GI) symptoms such as constipation, nausea, bloating, abdominal pain, and vomiting [31].”
Helisz, P., Dziubanek, G., Krupa-Kotara, K. H., Gwioździk, W., Grajek, M. K., & Głogowska‐Ligus, J. (2022) · Nutrients · doi:10.3390/nu14194185 · Cited by 9
“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 12
Akif, A., & Islam, M. R. (2026) · Comprehensive physiology · doi:10.1002/cph4.70100 · Cited by 12
“…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
Asbjornsdottir, B., Miranda-Ribera, A., Fiorentino, M. R., Konno, T., Çetinbaş, M., Lan, J., Sadreyev, R. I., Gudmundsson, L. S., Gottfreðsson, M., Lauth, B., et al. (2022) · Biomedicines · doi:10.3390/biomedicines11010091 · Cited by 7
Wang, Z., Lu, Y., Li, L., Wu, X., Liu, J., Tang, J., Wang, W., & Lu, L. (2023) · Psychology Research and Behavior Management · doi:10.2147/prbm.s429132 · Cited by 7
Simpson, S., Kimbrough, A., Peters, G., Wellmeyer, E., Mclellan, R., Walker, N., Jia, H., Hu, S., Iyer, M. R., Sathish, V., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.23.501268 · Cited by 6
“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
Metadata
- 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
- 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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