GUT MICROBIOME AND MENTAL HEALTH: FROM MECHANISMS TO APPLICATIONS
Main Article Content
Abstract
Aims: This review aims to summarize current evidence on the relationship between gut microbiota alterations and mood disorders, particularly depression and anxiety, and to highlight the potential of targeting the gut microbiome to develop interventions that improve outcomes in these conditions.
Methods: Relevant studies investigating gut microbiota composition, microbial metabolites, and microbiome-based interventions in depression and anxiety were analyzed to synthesize current findings and research directions.
Results: Compared with healthy individuals, patients with depression and/or anxiety exhibit reduced bacterial diversity and imbalances in genera such as Lactobacillus and Bifidobacterium. These alterations in microbial diversity are closely linked to the hypothalamic–pituitary–adrenal (HPA) axis, neurotransmitter modulation, and immune activity, and may contribute to the pathogenesis of mood disorders. Recent studies have also reported that microbiome-based strategies, including probiotics, prebiotics, and fecal microbiota transplantation, show potential as supportive treatments for mental health conditions.
Conclusion: Although growing evidence supports the role of the gut microbiome in mental health regulation, findings remain inconsistent across different populations. Further longitudinal and well–controlled studies are required to clarify causal relationships and support the development of personalized treatments.
Keywords
gut microbiome, depression, anxiety, gut-brain axis, probiotic
Article Details
References
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26. Nava GM, Friedrichsen HJ, Stappenbeck TS. Spatial organization of intestinal microbiota in the mouse ascending colon. ISME J. 2011;5(4):627-638. doi:10.1038/ismej.2010.161
27. Aizawa E, Tsuji H, Asahara T, et al. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J Affect Disord. 2016;202:254-257. doi:10.1016/J.JAD.2016.05.038
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32. Butler MI, Kittel-Schneider S, Wagner-Skacel J, Mörkl S, Clarke G. The Gut Microbiome in Anxiety Disorders. Current Psychiatry Reports. 2025;27(5):347-361. doi:10.1007/s11920-025-01604-w
33. Huang C, Feng S, Huo F, Liu H. Effects of Four Antibiotics on the Diversity of the Intestinal Microbiota. Microbiol Spectr. 2022;10(2):e01904-21. doi:10.1128/spectrum.01904-21
34. Lathakumari RH, Vajravelu LK, Satheesan A, Ravi S, Thulukanam J. Antibiotics and the gut microbiome: Understanding the impact on human health. Medicine in Microecology. 2024;20:100106. doi:10.1016/j.medmic.2024.100106
35. Cussotto S, Clarke G, Dinan TG, Cryan JF. Psychotropics and the Microbiome: a Chamber of Secrets. Psychopharmacology. 2019;236(5):1411-1432. doi:10.1007/S00213-019-5185-8
36. Huang F, Wu X. Brain Neurotransmitter Modulation by Gut Microbiota in Anxiety and Depression. Front Cell Dev Biol. Frontiers Media S.A. 2021;9. doi:10.3389/fcell.2021.649103
37. Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264-276. doi:10.1016/j.cell.2015.02.047
38. Doenyas C, Clarke G, Cserjési R. Gut–brain axis and neuropsychiatric health: recent advances. Sci Rep. 2025;15(1):1-4. doi:10.1038/s41598-025-86858-3
39. Olsen LK, Solis E, McIntire LK, Hatcher-Solis CN. Vagus nerve stimulation: mechanisms and factors involved in memory enhancement. Front Hum Neurosci. Frontiers Media SA. 2023;17. doi:10.3389/fnhum.2023.1152064
40. Han KM, Ham BJ. How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies. J Clin Neurol. 2021;17(4):503. doi:10.3988/jcn.2021.17.4.503
41. Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med. Springer Science and Business Media Deutschland GmbH. 2024;19(2):275-293. doi:10.1007/s11739-023-03374
42. Bertollo AG, Santos CF, Bagatini MD, Ignácio ZM. Hypothalamus-pituitary-adrenal and gut-brain axes in biological interaction pathway of the depression. Front Neurosci. Frontiers Media SA. 2025;19. doi:10.3389/fnins.2025.1541075
43. Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: A systematic review. Ann Gen Psychiatry. 2017;16(1):1-10. doi:10.1186/S12991-017-0138-2
44. Laudadio I, Fulci V, Palone F, Stronati L, Cucchiara S, Carissimi C. Quantitative Assessment of Shotgun Metagenomics and 16S rDNA Amplicon Sequencing in the Study of Human Gut Microbiome. OMICS. 2018;22(4):248-254. doi:10.1089/omi.2018.0013
45. Ranjan R, Rani A, Metwally A, McGee HS, Perkins DL. Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing. Biochem Biophys Res Commun. 2016;469(4):967-977. doi:10.1016/j.bbrc.2015.12.083
46. Carruthers L V., Moses A, Adriko M, et al. The impact of storage conditions on human stool 16S rRNA microbiome composition and diversity. PeerJ. 2019;(12):e8133. doi:10.7717
47. Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev. 2019;102:13. doi:10.1016/j.neubiorev.2019.03.023
48. Morales-Torres R, Carrasco-Gubernatis C, Grasso-Cladera A, Cosmelli D, Parada FJ, Palacios-García I. Psychobiotic Effects on Anxiety Are Modulated by Lifestyle Behaviors: A Randomized Placebo-Controlled Trial on Healthy Adults. Nutrients. 2023;15(7). doi:10.3390/nu15071706
49. Ferrari S, Mulè S, Parini F, et al. The influence of the gut-brain axis on anxiety and depression: A review of the literature on the use of probiotics. J Tradit Complement Med. National Taiwan University. 2024;14(3):237-255. doi:10.1016/j.jtcme.2024.03.011
50. Chinna Meyyappan A, Forth E, Wallace CJK, Milev R. Effect of fecal microbiota transplant on symptoms of psychiatric disorders: A systematic review. BMC Psychiatry. 2020;20(1):1-19. doi:10.1186/S12888-020-02654-5
51. Kelly JR, Borre Y, O’ Brien C, et al. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016;82:109-118. doi:10.1016/j.jpsychires.2016.07.019
52. Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Molecular Psychiatry. 2016;21(6):786-796. doi:10.1038/mp.2016.44
53. Jovel J, Patterson J, Wang W, et al. Characterization of the Gut Microbiome Using 16S or Shotgun Metagenomics. Front Microbiol. 2016;7(APR):459. doi:10.3389/fmicb.2016.00459
54. El-Salhy M, Mazzawi T. Fecal microbiota transplantation for managing irritable bowel syndrome. Expert Rev Gastroenterol Hepatol. 2018;12(5):439-445. doi:10.1080/17474124.2018.1447380
55. Vaher K, Bogaert D, Richardson H, Boardman JP. Microbiome-gut-brain axis in brain development, cognition and behavior during infancy and early childhood. Developmental Review. Elsevier Inc. 2022;66. doi:10.1016/j.dr.2022.101038
56. Fox M, Lee SM, Wiley KS, et al. Development of the infant gut microbiome predicts temperament across the first year of life. Dev Psychopathol. 2022;34(5):1914-1925. doi:10.1017/S0954579421000456
57. Wu J, Singleton SS, Bhuiyan U, Krammer L, Mazumder R. Multi-omics approaches to studying gastrointestinal microbiome in the context of precision medicine and machine learning. Front Mol Biosci. Frontiers Media SA. 2023;10. doi:10.3389/fmolb.2023.133737
2. World Health Organization. Anxiety disorders. Accessed March 28, 2025. Available from: https://www.who.int/news-room/fact-sheets/detail/anxiety-disorders
3. Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018;1693 (Pt B):128. doi:10.1016/j.brainres.2018.03.015
4. Clerici L, Bottari D, Bottari B. Gut Microbiome, Diet and Depression: Literature Review of Microbiological, Nutritional and Neuroscientific Aspects. Curr Nutr Rep. 2025;14(1):1-14. doi:10.1007/S13668-025-00619-2
5. Rosenberg E. Diversity of bacteria within the human gut and its contribution to the functional unity of holobionts. npj Biofilms Microbiomes. 2024;10(1):5. doi:10.1038/s41522-024-00580-y
6. Simpson CA, Diaz-Arteche C, Eliby D, Schwartz OS, Simmons JG, Cowan CSM. The gut microbiota in anxiety and depression–A systematic review. Clin Psychol Rev. 2021;83:101943. doi:10.1016/j.cpr.2020.101943
7. Peirce JM, Alviña K. The role of inflammation and the gut microbiome in depression and anxiety. J Neurosci Res. 2019;97(10):1223-1241. doi:10.1002/jnr.24476
8. Nguyễn TTN, Đoàn TTH, Lưu ĐNA. Lợi khuẩn-cytokines và trầm cảm. Thai Binh Journal of Medicine and Pharmacy. 2023;(06).
9. Kumar A, Pramanik J, Goyal N, et al. Gut Microbiota in Anxiety and Depression: Unveiling the Relationships and Management Options. Pharmaceuticals. Multidisciplinary Digital Publishing Institute (MDPI). 2023;16(4). doi:10.3390/ph16040565
10. Cheung SG, Goldenthal AR, Uhlemann AC, Mann JJ, Miller JM, Sublette ME. Systematic Review of Gut Microbiota and Major Depression. Front Psychiatry. 2019;10(FEB):34. doi:10.3389/fpsyt.2019.00034
11. Sanada K, Nakajima S, Kurokawa S, et al. Gut microbiota and major depressive disorder: A systematic review and meta-analysis. J Affect Disord. 2020;266:1-13. doi:10.1016/j.jad.2020.01.102
12. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. doi:10.3389/fendo.2020.00025
13. O’Riordan KJ, Collins MK, Moloney GM, et al. Short chain fatty acids: Microbial metabolites for gut-brain axis signalling. Mol Cell Endocrinol. Elsevier Ireland Ltd. 2022;546. doi:10.1016/j.mce.2022.111572
14. Tarracchini C, Lugli GA, Mancabelli L, et al. Exploring the vitamin biosynthesis landscape of the human gut microbiota. Gilbert JA, ed. mSystems. 2024;9(10):e00929-24. doi:10.1128/msystems.00929-24
15. Hou K, Wu ZX, Chen XY, et al. Microbiota in health and diseases. Signal Transduct Target Ther. Springer Nature. 2022;7(1). doi:10.1038/s41392-022-00974-4
16. Qu S, Yu Z, Zhou Y, et al. Gut microbiota modulates neurotransmitter and gut-brain signaling. Microbiol Res. 2024;287:127858. doi:10.1016/j.micres.2024.127858
17. Choden T, Cohen NA. The gut microbiome and the immune system. Open Exploration. 2022;3(3):219-233. doi:10.37349/emed.2022.00087
18. Järbrink-Sehgal E, Andreasson A. The gut microbiota and mental health in adults. Curr Opin Neurobiol. 2020;62:102-114. doi:10.1016/j.conb.2020.01.016
19. Hoang TH, Le HD, Nguyen TTN, Nguyen TN. The first step comparative analysis of gut microbiota in human with type 2 diabetes and non-diabetic in Vietnam. In: Vietnam National Conference on Biotechnology. 2021.
20. Rinninella E, Raoul P, Cintoni M, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms. 2019;7(1). doi:10.3390/microorganisms7010014
21. Sheng Y, Wang J, Gao Y, et al. Combined analysis of cross-population healthy adult human microbiome reveals consistent differences in gut microbial characteristics between Western and non-Western countries. Comput Struct Biotechnol J. 2024;23:87-95. doi:10.1016/j.csbj.2023.11.047
22. Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cellular and Molecular Life Sciences. Birkhauser Verlag AG. 2019;76(3):473-493. doi:10.1007/s00018-018-2943-4
23. Donaldson GP, Lee SM, Mazmanian SK. Gut biogeography of the bacterial microbiota. Nature Reviews Microbiology. 2015;14(1):20-32. doi:10.1038/nrmicro3552
24. Jensen BAH, Heyndrickx M, Jonkers D, et al. Small intestine vs. colon ecology and physiology: Why it matters in probiotic administration. Cell Rep Med. Cell Press. 2023;4(9). doi:10.1016/j.xcrm.2023.101190
25. Dieterich W, Schink M, Zopf Y. Microbiota in the Gastrointestinal Tract. Med Sci (Basel). NLM (Medline). 2018;6(4). doi:10.3390/medsci6040116
26. Nava GM, Friedrichsen HJ, Stappenbeck TS. Spatial organization of intestinal microbiota in the mouse ascending colon. ISME J. 2011;5(4):627-638. doi:10.1038/ismej.2010.161
27. Aizawa E, Tsuji H, Asahara T, et al. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J Affect Disord. 2016;202:254-257. doi:10.1016/J.JAD.2016.05.038
28. Zhao Q, Baranova A, Cao H, Zhang F. Gut microbiome and major depressive disorder: insights from two-sample Mendelian randomization. BMC Psychiatry. 2024;24(1):493. doi:10.1186/s12888-024-05942-6
29. Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186-194. doi:10.1016/J.BBI.2015.03.016
30. Parker BJ, Wearsch PA, Veloo ACM, Rodriguez-Palacios A. The Genus Alistipes: Gut Bacteria With Emerging Implications to Inflammation, Cancer, and Mental Health. Front Immunol. Frontiers Media S.A. 2020;11. doi:10.3389/fimmu.2020.00906
31. Gomez-Nguyen A, Basson AR, Dark-Fleury L, et al. Parabacteroides distasonis induces depressive-like behavior in a mouse model of Crohn’s disease. Brain Behav Immun. 2021;98:245-250. doi:10.1016/j.bbi.2021.08.218
32. Butler MI, Kittel-Schneider S, Wagner-Skacel J, Mörkl S, Clarke G. The Gut Microbiome in Anxiety Disorders. Current Psychiatry Reports. 2025;27(5):347-361. doi:10.1007/s11920-025-01604-w
33. Huang C, Feng S, Huo F, Liu H. Effects of Four Antibiotics on the Diversity of the Intestinal Microbiota. Microbiol Spectr. 2022;10(2):e01904-21. doi:10.1128/spectrum.01904-21
34. Lathakumari RH, Vajravelu LK, Satheesan A, Ravi S, Thulukanam J. Antibiotics and the gut microbiome: Understanding the impact on human health. Medicine in Microecology. 2024;20:100106. doi:10.1016/j.medmic.2024.100106
35. Cussotto S, Clarke G, Dinan TG, Cryan JF. Psychotropics and the Microbiome: a Chamber of Secrets. Psychopharmacology. 2019;236(5):1411-1432. doi:10.1007/S00213-019-5185-8
36. Huang F, Wu X. Brain Neurotransmitter Modulation by Gut Microbiota in Anxiety and Depression. Front Cell Dev Biol. Frontiers Media S.A. 2021;9. doi:10.3389/fcell.2021.649103
37. Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264-276. doi:10.1016/j.cell.2015.02.047
38. Doenyas C, Clarke G, Cserjési R. Gut–brain axis and neuropsychiatric health: recent advances. Sci Rep. 2025;15(1):1-4. doi:10.1038/s41598-025-86858-3
39. Olsen LK, Solis E, McIntire LK, Hatcher-Solis CN. Vagus nerve stimulation: mechanisms and factors involved in memory enhancement. Front Hum Neurosci. Frontiers Media SA. 2023;17. doi:10.3389/fnhum.2023.1152064
40. Han KM, Ham BJ. How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies. J Clin Neurol. 2021;17(4):503. doi:10.3988/jcn.2021.17.4.503
41. Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med. Springer Science and Business Media Deutschland GmbH. 2024;19(2):275-293. doi:10.1007/s11739-023-03374
42. Bertollo AG, Santos CF, Bagatini MD, Ignácio ZM. Hypothalamus-pituitary-adrenal and gut-brain axes in biological interaction pathway of the depression. Front Neurosci. Frontiers Media SA. 2025;19. doi:10.3389/fnins.2025.1541075
43. Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: A systematic review. Ann Gen Psychiatry. 2017;16(1):1-10. doi:10.1186/S12991-017-0138-2
44. Laudadio I, Fulci V, Palone F, Stronati L, Cucchiara S, Carissimi C. Quantitative Assessment of Shotgun Metagenomics and 16S rDNA Amplicon Sequencing in the Study of Human Gut Microbiome. OMICS. 2018;22(4):248-254. doi:10.1089/omi.2018.0013
45. Ranjan R, Rani A, Metwally A, McGee HS, Perkins DL. Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing. Biochem Biophys Res Commun. 2016;469(4):967-977. doi:10.1016/j.bbrc.2015.12.083
46. Carruthers L V., Moses A, Adriko M, et al. The impact of storage conditions on human stool 16S rRNA microbiome composition and diversity. PeerJ. 2019;(12):e8133. doi:10.7717
47. Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev. 2019;102:13. doi:10.1016/j.neubiorev.2019.03.023
48. Morales-Torres R, Carrasco-Gubernatis C, Grasso-Cladera A, Cosmelli D, Parada FJ, Palacios-García I. Psychobiotic Effects on Anxiety Are Modulated by Lifestyle Behaviors: A Randomized Placebo-Controlled Trial on Healthy Adults. Nutrients. 2023;15(7). doi:10.3390/nu15071706
49. Ferrari S, Mulè S, Parini F, et al. The influence of the gut-brain axis on anxiety and depression: A review of the literature on the use of probiotics. J Tradit Complement Med. National Taiwan University. 2024;14(3):237-255. doi:10.1016/j.jtcme.2024.03.011
50. Chinna Meyyappan A, Forth E, Wallace CJK, Milev R. Effect of fecal microbiota transplant on symptoms of psychiatric disorders: A systematic review. BMC Psychiatry. 2020;20(1):1-19. doi:10.1186/S12888-020-02654-5
51. Kelly JR, Borre Y, O’ Brien C, et al. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016;82:109-118. doi:10.1016/j.jpsychires.2016.07.019
52. Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Molecular Psychiatry. 2016;21(6):786-796. doi:10.1038/mp.2016.44
53. Jovel J, Patterson J, Wang W, et al. Characterization of the Gut Microbiome Using 16S or Shotgun Metagenomics. Front Microbiol. 2016;7(APR):459. doi:10.3389/fmicb.2016.00459
54. El-Salhy M, Mazzawi T. Fecal microbiota transplantation for managing irritable bowel syndrome. Expert Rev Gastroenterol Hepatol. 2018;12(5):439-445. doi:10.1080/17474124.2018.1447380
55. Vaher K, Bogaert D, Richardson H, Boardman JP. Microbiome-gut-brain axis in brain development, cognition and behavior during infancy and early childhood. Developmental Review. Elsevier Inc. 2022;66. doi:10.1016/j.dr.2022.101038
56. Fox M, Lee SM, Wiley KS, et al. Development of the infant gut microbiome predicts temperament across the first year of life. Dev Psychopathol. 2022;34(5):1914-1925. doi:10.1017/S0954579421000456
57. Wu J, Singleton SS, Bhuiyan U, Krammer L, Mazumder R. Multi-omics approaches to studying gastrointestinal microbiome in the context of precision medicine and machine learning. Front Mol Biosci. Frontiers Media SA. 2023;10. doi:10.3389/fmolb.2023.133737