Mikrobiyota ve Ruh Sağlığı İlişkisi: Bütüncül Bir Bakış

Abstract

İnsan bağırsağındaki mikroorganizmalar, mikrobiyota–bağırsak–beyin ekseni aracılığıyla beyin işlevlerini ve ruh sağlığını düzenlemektedir. Bu çift yönlü iletişim ağı; sinirsel (örn. vagus siniri), endokrin (örn. kortizol, serotonin), immün (örn. sitokinler) ve mikrobiyal metabolit (örn. kısa zincirli yağ asitleri) yollarını kapsamaktadır. Son dönem çalışmalar, bağırsak mikrobiyotasındaki dengesizliğin depresyon, anksiyete, otizm spektrum bozuklukları, şizofreni, bipolar bozukluk ve travma sonrası stres bozukluğu gibi psikiyatrik bozuklukların patogenezinde rol oynadığını ortaya koymaktadır. Azalmış mikrobiyal çeşitlilik, yararlı kısa zincirli yağ asidi üreten bakterilerin tükenmesi ve proinflamatuvar taksonların artışı ile karakterize olan değişmiş mikrobiyal profillerin, nöropsikiyatrik semptomatoloji ile tutarlı biçimde ilişkili olduğu saptanmıştır. Çalışmalar, probiyotikler, prebiyotikler ve diyet değişiklikleri gibi mikrobiyota temelli müdahalelerin ruh sağlığı üzerinde etkili olabileceğini göstermekte; bu da "psikobiyotikler" kavramının ortaya çıkmasına yol açmaktadır. Bu derleme, bağırsak mikrobiyotası ile psikiyatrik bozukluklar arasındaki ilişkiyi açıklayan mekanistik temellere dair kapsamlı bir sentez sunmakta ve mikrobiyota temelli stratejilerin terapötik potansiyelini değerlendirmektedir. Ayrıca, kişiye özel psikobiyotik tedaviler, bağırsak mikrobiyotasından türetilmiş biyobelirteçler ve bunların psikiyatrik bakımda pratik uygulamaları gibi yeni gelişmeleri de incelemektedir. Bütüncül bir bakış açısını benimseyen bu çalışma, disiplinler arası etkileşimi güçlendirmeyi ve bağırsak ile beyin arasındaki dinamik ilişkinin temellerine dayalı bütünleşik ruh sağlığı yaklaşımlarının gelişimine katkı sağlamayı amaçlamaktadır.

Keywords

• mikrobiyota-bağırsak-beyin ekseni
• psikobiyotikler
• psikiyatrik bozukluklar
• ruh sağlığı

Relationship Between Microbiota and Mental Health: A Holistic View

Abstract

The microorganisms in the human intestine regulate brain function and mental health through the microbiota-gut-brain axis. This bidirectional communication network encompasses neural (e.g., vagus nerve), endocrine (e.g., cortisol, serotonin), immune (e.g., cytokines), and microbial metabolite (e.g., short-chain fatty acids) pathways. Recent studies highlight the role of gut dysbiosis in the pathogenesis of psychiatric disorders such as depression, anxiety, autism spectrum disorders, schizophrenia, bipolar disorder, and post-traumatic stress disorder. Altered microbial profiles—marked by reduced microbial diversity, depletion of beneficial short-chain fatty acids-producing bacteria, and increased pro-inflammatory taxa—have been consistently associated with neuropsychiatric symptomatology. Studies have shown that microbiota interventions such as probiotics, prebiotics and dietary changes can affect mental health, giving rise to the concept of 'psychobiotics'. This narrative review presents a comprehensive synthesis of the mechanistic underpinnings linking gut microbiota to psychiatric disorders and evaluates the therapeutic potential of microbiota-based strategies. It also explores new developments such as tailored psychobiotic treatments, biomarkers derived from the gut microbiota, and their practical applications in psychiatric care. By adopting an integrative perspective, this review aims to bridge disciplines and foster the development of holistic mental health care approaches grounded in the dynamic interplay between the gut and the brain.

Keywords

• microbiota-gut-brain axis
• psychobiotics
• psychiatric disorders
• mental health

References

1. Agus A, Planchais J, Sokol H (2018) Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe, 23:716–724.
2. Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, Jafari P, Akbari H, Taghizadeh M et al. (2016) Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition, 32:315–320.
3. Allen AP, Hutch W, Borre YE, Kennedy PJ, Temko A, Boylan G et al. (2016) Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Transl Psychiatry, 6:e939.
4. Averina OV, Poluektova EU, Zorkina YA, Kovtun AS, Danilenko VN (2024) Human gut microbiota for diagnosis and treatment of depression. Int J Mol Sci, 25:5782.
5. Bajaj JS, Sikaroodi M, Fagan A, Heuman D, Gilles H, Gavis EA et al. (2019) Posttraumatic stress disorder is associated with altered gut microbiota that modulates cognitive performance in veterans with cirrhosis. Am J Physiol Gastrointest Liver Physiol, 317:G661–G669.
6. Berding K, Bastiaanssen TF, Moloney GM, Boscaini S, Strain CR, Anesi A et al. (2023) Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population. Mol Psychiatry, 28:601-610.
7. Bharwani A, Mian MF, Foster JA, Surette MG, Bienenstock J, Forsythe P (2016) Structural & functional consequences of chronic psychosocial stress on the microbiome & host. Psychoneuroendocrinology, 63:217-227.
8. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG et al. (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A, 108:16050–16055.

9. Burokas A, Arboleya S, Moloney RD, Peterson VL, Murphy K, Clarke G et al. (2017) Targeting the microbiota-gut-brain axis: Prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry, 82:472–487.
10. Cheung SG, Goldenthal AR, Uhlemann AC, Mann JJ, Miller JM, Sublette ME (2019) Systematic review of gut microbiota and major depression. Front Psychiatry, 10:34.
11. Chiu CY, Miller SA (2019) Clinical metagenomics. Nat Rev Genet, 20:341–355.
12. Cryan JF, O'Riordan KJ, Cowan CS, Sandhu KV, Bastiaanssen TF, Boehme M et al. (2019) The microbiota-gut-brain axis. Physiol Rev. 99:1877–2013
13. Dalile B, Van Oudenhove L, Vervliet B, Verbeke K (2019) The role of short-chain fatty acids in microbiota–gut–brain communication. Nat Rev Gastroenterol Hepatol, 16:461–478.
14. Delanote J, Correa Rojo A, Wells PM, Steves CJ, Ertaylan G (2024) Systematic identification of the role of gut microbiota in mental disorders: a TwinsUK cohort study. Sci Rep. 14:3626
15. Dickerson FB, Stallings CR, Origoni AE, Katsafanas E, Savage CL, Schweinfurth LA et al. (2014) Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: A randomized, placebo-controlled trial. Prim Care Companion CNS Disord, 16:PCC.13m01579.
16. Dickerson F, Adamos M, Katsafanas E, Khushalani S, Origoni A, Savage C et al. (2018) Adjunctive probiotic microorganisms to prevent rehospitalization in patients with acute mania: A randomized controlled trial. Bipolar Disord, 20:614–621.
17. Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry, 74:720–726.
18. Gan H, Su Y, Zhang L, Huang G, Lai C, Lv Y, Li Y (2023) Questionnaire-based analysis of autism spectrum disorders and gastrointestinal symptoms in children and adolescents: a systematic review and meta-analysis. Front Pediatr, 11:1120728.
19. Gebrayel P, Nicco C, Al Khodor S, Bilinski J, Caselli E, Comelli EM et al. (2022) Microbiota medicine: towards clinical revolution. J Transl Med, 20:111.
20. Gibbons SM, Gurry T, Lampe JW, Chakrabarti A, Dam V, Everard A et al. (2022) Perspective: leveraging the gut microbiota to predict personalized responses to dietary, prebiotic, and probiotic interventions. Adv Nutr, 13:1450–1461.
21. Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ et al. (2017) Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol, 14:491–502.
22. Goldiș A, Dragomir R, Mercioni MA, Goldiș C, Sirca D, Enătescu I et al. (2025) Personalized microbiome modulation to improve clinical outcomes in pediatric inflammatory bowel disease: a multi-omics and interventional approach. Microorganisms, 13:1047.
23. Hilimire MR, DeVylder JE, Forestell CA (2015) Fermented foods, neuroticism, and social anxiety: An interaction model. Psychiatry Res, 228:203–208.
24. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T et al. (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell, 155:1451–1463.
25. Huang R, Wang K, Hu J (2016) Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients, 8:483.
26. Huang YY, Wu YP, Jia XZ, Lin J, Xiao LF, Liu DM et al. (2022) Lactiplantibacillus plantarum DMDL 9010 alleviates dextran sodium sulfate (DSS)-induced colitis and behavioral disorders by facilitating microbiota-gut-brain axis balance. Food Funct, 13:411–424.
27. Jacka FN, O’Neil A, Opie R, Itsiopoulos C, Cotton S, Mohebbi M et al. (2017) A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med, 15:23.
28. Jiang HY, Zhang X, Yu ZH, Zhang Z, Deng M, Zhao JH, Ruan B (2018) Altered gut microbiota profile in patients with generalized anxiety disorder. J Psychiatr Res, 104:130–136.
29. Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y et al. (2015) Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun, 48:186–194.
30. Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A et al. (2017) Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome, 5:10.
31. Karagözlü S, Dalgıç B, İşeri E (2022) The relationship of severity of autism with gastrointestinal symptoms and serum zonulin levels in autistic children. J Autism Dev Disord, 52:623-629.
32. Kelly JR, Borre Y, O’Brien C, Patterson E, El Aidy S, Deane J et al. (2016) Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res, 82:109–118.
33. Khan M, Bhowmick B, Ahmad S, Sachdeva P, Ibrahim M, Srivastava P (2025) Rebalancing the gut ecosystem: A comprehensive review of faecal microbiota transplantation. Int J Med Public Health, 15:89–97.
34. Kodidala SR, Kaur H, Manjunath S, Akula GR (2024) Unraveling the intricacies of the gut-brain axis: from physiology to psychology and obesity. Siberian Scientific Medical Journal, 44(5):19–23.
35. Korteniemi J, Karlsson L, Aatsinki A (2023) Systematic review: Autism spectrum disorder and the gut microbiota. Acta Psychiatr Scand, 148:242–254.
36. Liu L, Wang H, Chen X, Zhang Y, Zhang H, Xie P (2023) Gut microbiota and its metabolites in depression: from pathogenesis to treatment. EBioMedicine, 90:104527..
37. Louis P, Hold GL, Flint HJ (2014) The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol, 12:661–672.
38. Malan-Müller S, Valles-Colomer M, Raes J, Lowry CA, Seedat S, Hemmings SM (2018) The gut microbiome and mental health: Implications for anxiety- and trauma-related disorders. OMICS, 22:90–107.
39. McGuinness AJ, Davis JA, Dawson SL, Loughman A, Collier F, O’hely M et al. (2022) A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia. Mol Psychiatry, 27:1920–1935.
40. Mendez‐Hernandez R, Braga I, Bali A, Yang M, de Lartigue G (2025) Vagal sensory gut–brain pathways that control eating—satiety and beyond. Compr Physiol, 15:e70010.
41. Meneses do Rêgo AC, Araújo-Filho I (2025) Microbiome-guided antidepressant therapy: The future of personalized psychiatry. Biomed J Sci Tech Res, 60:52785–52794.
42. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A et al. (2011) Assessment of psychotropic-like properties of a probiotic formulation in rats and humans. Br J Nutr, 105:755–764.
43. Młynarska E, Barszcz E, Budny E, Gajewska A, Kopeć K, Wasiak J et al. (2025) The gut–brain–microbiota connection and its role in autism spectrum disorders. Nutrients, 17:1135.
44. Mohr AE, Basile AJ, Meli’sa SC, Sweazea KL, Carpenter KC (2020) Probiotic supplementation has a limited effect on circulating immune and inflammatory markers in healthy adults: a systematic review of randomized controlled trials. J Acad Nutr Diet, 120:548–564.
45. Musazadeh V, Zarezadeh M, Faghfouri AH, Keramati M, Jamilian P, Jamilian P et al. (2023) Probiotics as an effective therapeutic approach in alleviating depression symptoms: an umbrella meta-analysis. Crit Rev Food Sci Nutr, 63:8292-8300.
46. Nikolova VL, Smith MR, Hall LJ, Cleare AJ, Stone JM, Young AH (2021) Perturbations in gut microbiota composition in psychiatric disorders: a review and meta-analysis.. JAMA Psychiatry, 78:1343–1354.
47. Painold A, Mörkl S, Kashofer K, Halwachs B, Dalkner N, Bengesser S et al. (2019) A step ahead: Exploring the gut microbiota in inpatients with bipolar disorder during a depressive episode. Bipolar Disord, 21:40–49.
48. Pantazi AC, Balasa AL, Mihai CM, Chisnoiu T, Lupu VV, Kassim MAK et al. (2023) Development of gut microbiota in the first 1000 days after birth and potential ınterventions. Nutrients, 15:3647.
49. Parletta N, Zarnowiecki D, Cho J, Wilson A, Bogomolova S, Villani A et al. (2019) A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutr Neurosci, 22:474-487.
50. Phelps JR, Siemers SV, El-Mallakh RS (2013) The ketogenic diet for type II bipolar disorder. Neurocase, 19:423–426.
51. Pinto-Sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT et al. (2017) Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology, 153:448.e8–459.e8.
52. Qian L, He X, Liu Y, Gao F, Lu W, Fan Y et al. (2023) Longitudinal gut microbiota dysbiosis underlies olanzapine-ınduced weight gain. Microbiol Spectr, 11:e0005823.
53. Radjabzadeh D, Bosch JA, Uitterlinden AG, Zwinderman AH, Ikram MA, van Meurs JB et al. (2022) Gut microbiome-wide association study of depressive symptoms. Nat Commun, 13:7128.
54. Ritz NL, Brocka M, Butler MI, Cowan CS, Barrera-Bugueño C, Turkington C, J et al. (2024) Social anxiety-associated gut microbiota increases social fear. Proc Natl Acad Sci U S A, 121:e2308706120.
55. Sălcudean A, Bodo CR, Popovici RA, Cozma MM, Păcurar M, Crăciun RE et al. (2025) Neuroinflammation-a crucial factor in the pathophysiology of depression-a comprehensive review. Biomolecules, 15:502.
56. Schmidt K, Cowen PJ, Harmer CJ, Tzortzis G, Errington S, Burnet PW (2015) Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl), 232:1793–1801.
57. Seethaler B, Nguyen NK, Basrai M, Kiechle M, Walter J, Delzenne NM et al. (2022) Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial Am J Clin Nutr, 116:928–942.
58. Settanni CR, Ianiro G, Bibbò S, Cammarota G, Gasbarrini A (2021) Gut microbiota alteration and modulation in psychiatric disorders: Current evidence on fecal microbiota transplantation. Prog Neuropsychopharmacol Biol Psychiatry, 109:110258.
59. Severance EG, Yolken RH, Eaton WW (2016) Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling. Schizophr Res, 176:23–35.
60. Simpson CA, Diaz-Arteche C, Eliby D, Schwartz OS, Simmons JG, Cowan CS (2021) The gut microbiota in anxiety and depression: a systematic review. Clin Psychol Rev, 83:101943.
61. Slavin J (2013) Fiber and prebiotics: Mechanisms and benefits. Nutrients, 5:1417–1435.
62. Sochacka K, Kotowska A, Lachowicz-Wiśniewska S (2024) The role of gut microbiota, nutrition, and physical activity in depression and obesity-interdependent mechanisms/co-occurrence. Nutrients, 16:1039.
63. Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J et al. (2017) New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome, 5:24.
64. Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN et al. (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in miceJ Physiol, 558:263–275.
65. Sun J, Wang F, Hu X, Yang C, Xu H, Yao Y, Liu J (2018) Clostridium butyricum attenuates chronic unpredictable mild stress-induced depressive-like behavior in mice via the gut-brain axis. J Agric Food Chem, 66:8415–8421.
66. Theriot C, Thanissery R, O'Flaherty S, Barrangou R (2022) Probiotic colonization dynamics after oral consumption of VSL#3® by antibiotic-treated mice. Microbiome Res Rep, 1:21.
67. Ting EYC, Yang AC, Tsai SJ (2020) Role of interleukin-6 in depressive disorder.. Int J Mol Sci, 21:2194.
68. Valles-Colomer M, Falony G, Darzi Y, Tigchelaar EF, Wang J, Tito RY et al. (2019) The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol, 4:623–632.
69. Vendrik KEW, Ooijevaar RE, de Jong PRC, Laman JD, van Oosten BW, van Hilten JJ et al. (2020) Fecal microbiota transplantation in neurological disorders. Front Cell Infect Microbiol, 10:98.
70. Wei N, Ju M, Su X, Zhang Y, Huang Y, Rao X et al. (2024) Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice. Schizophrenia (Heidelb)., 10:44.
71. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L et al. (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 161:264–276.
72. Yaqub MO, Jain A, Joseph CE, Edison LK (2025) Microbiome-driven therapeutics: from gut health to precision medicine. Gastrointest Disord, 7:7.
73. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M et al. (2012) Human gut microbiome viewed across age and geography. Nature, 486:222–227.
74. Yong SJ, Tong T, Chew J, Lim WL (2020) Antidepressive mechanisms of probiotics and their therapeutic potential. Front Neurosci, 13:1361.
75. Zheng P, Zeng B, Zhou C, Liu M, Fang Z, Xu X et al. (2016) Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol Psychiatry, 21:786-796.
76. Zhu S, Jiang Y, Xu K, Cui M, Ye W, Zhao G et al. (2020) The progress of gut microbiome research related to brain disorders. J Neuroinflammation, 17:25.