INVESTİGATİON OF THE EFFECTS OF THE GUT-BRAİN AXİS ON BRAİN AND MENTAL HEALTH

Öz

There is a bidirectional and continuous relationship and communication between the brain and the gut. The gut-brain axis communicates not only through the microbiota but also via the autonomic nervous system. Microorganisms in the gut microbiota are known to contribute to the production of certain neurotransmitters that play roles in brain function, which may, in turn, influence mental health. Through this interaction, the gut microbiota and gastrointestinal system components play significant roles in human health. A healthy functioning of the gut-brain axis is essential for supporting the immune system, regulating mood, and maintaining cognitive and immune health. Recent studies highlight a connection and causality between the gut-brain-microbiota axis and neurological disorders such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and autism spectrum disorder, as well as psychiatric disorders like depression, anxiety, schizophrenia, and bipolar disorder. This paper reviews the impact of the gut-brain-microbiota axis on brain and mental health, emotion-thought-behavior systems, and its effects on neurological and psychiatric disorders.

Anahtar Kelimeler

• Gut-brain axis
• microbiota
• psychiatric disorders
• neurological disorders

BEYİN-BAĞIRSAK AKSININ, BEYİN VE RUH SAĞLIĞI ÜZERİNDEKİ ETKİSİNİN İNCELENMESİ

Öz

Beyin ve bağırsak arasında çift yönlü ve sürekli bir ilişki ve iletişim bulunmaktadır. Beyin-bağırsak aksı mikrobiyota aracılığıyla iletişim kurabilmenin yanında otonom sinir sistemi aracılığıyla da iletişim kurmaktadır. Bağırsak mikrobiyotasında bulunan mikroorganizmaların, beyin üzerinde rolü olan bazı nörotransmitterlerin üretimine destek olduğu bilinmektedir ve bu yolla da ruh sağlığını etkileyebileceği düşünülmektedir. Bu ilişki sayesinde bağırsak mikrobiyotası ve gastrointestinal sistem unsurları insan sağlığı üzerinde rol oynamaktadır. Beyin-bağırsak aksının sağlıklı işlev gösterebilmesi; bağışıklık sisteminin desteklenmesi, ruh halinin düzenlenmesi ve bilişsel/immün sağlığın korunmasında etkin rol almaktadır. Son yıllarda yapılan araştırmalar değerlendirildiğinde; beyin-bağırsak-mikrobiyota aksıyla parkinson, alzheimer, multipl skleroz, otizm gibi nörolojik bozukluklar ve depresyon, anksiyete, şizofreni, bipolar bozukluk gibi psikiyatrik bozukluklar arasında bir bağlantı ve nedensellik bulunmaktadır. Bu makalede beyin-bağırsak-mikrobiyota aksının beyin ve ruh sağlığı, duygu-düşünce-davranış sistemleri ve nörolojik ve psikiyatrik bozukluklar üzerine etkisi gözden geçirilmiştir.

Kaynakça

1. 1. Liang, S., Wu, X. and Jin, F. (2018). Gut-brain psychology: rethinking psychology from the microbiota–gut–brain axis. Frointers in Integrative Neuroscience, (12)33. Https://doi.org/10.3389/fnint.2018.00033
2. 2. Doğan, A., Yaşar, S., Kayhan, S., Kırmızıgöz, Ş. and Kaplan, A. (2018). Bağırsak-beyin aksı. Türk Nöroşir Derg., 28(3): 377-379.
3. 3. Bercik, P., Collins, S.M. ve Verdu, F. (2012). Microbes and the gut-brain axis. Neurogastroenterology and Motility, (24)5: 405-413. Https://doi.org/10.1111/j.1365-2982.2012.01906.x
4. 4. Evrensel, A. Ve Ceylan, M.E. (2015). Bağırsak beyin ekseni: Psikiyatrik bozukluklarda bağırsak mikrobiyotasının rolü. Psikiyatride Güncel Yaklaşımlar, 7(4): 461-472. Https://doi.org/10.5455/cap.20150128123852
5. 5. 5. Ekici, M. ve Baş-Ekici, H. (2021). Beyin-bağırsak-mikrobiyota ekseni: genel bakış. Bozok Vet Sci., (2)1: 16-22.
6. 6. Góralczyk-Bińkowska, A., Szmajda-Krygier, D. Ve Kozłowska, E. (2022). The microbiota–gut–brain axis in psychiatric disorders. Int. J. Mol. Sci., 23(19): 11245. Https://doi.org/10.3390/ijms231911245
7. 7. Holzer, P. ve Farzi, A. (2014). Neuropeptides and the microbiota-gut-brain axis. In: Lyte, M., Cryan, J. Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease. Advances in Experimental Medicine and Biology, 817. Springer, New York, NY. Https://doi.org/10.1007/978-1-4939-0897-4_9
8. 8. Aljeradat, B., Kumar, D., Abdulmuizz, S., Kundu, M., Almealawy, Y.F., Batarseh, D.R., Atallah, O., Ennabe, M., Alsarafand, M., Alan, A. Ve Weinand, M. (2024). Neuromodulation and the gut–brain axis: therapeutic mechanisms and ımplications for gastrointestinal and neurological disorders. Pathophysiology, (31)2: 244-268. Https://doi.org/10.3390/pathophysiology31020019

9. 9. Zheng, Y., Bonfili, L., Wei, T. Ve Eleuteri, A.M. (2023). Understanding the gut–brain axis and its therapeutic implications for neurodegenerative disorders. Nutrients, 5(21): 4631. Https://doi.org/10.3390/nu15214631
10. 10. Tan, O. (2023). Psikofarmakoloji. İstanbul: Nobel Akademik Yayıncılık.
11. 11. Arneth, B.M. (2018). Gut–brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function. Postgraduate Medical Journal, (94)1114: 446-452. Https://doi.org/10.1136/postgradmedj-2017-135424
12. 12. Kang, P. ve Wang, A.Z. (2024). Microbiota–gut–brain axis: the mediator of exercise and brain health. Psychoradiology, (4) kkae007. Https://doi.org/10.1093/psyrad/kkae007
13. 13. Saulnier, D.M., Ringel, Y., Heyman, M.B., Foster, J.A., Bercik, P., Shulman, R.J…Guarner, F. (2012). The intestinal microbiome, probiotics and prebiotics in neurogastroenterology. Gut Microbes, 4(1): 17–27. Https://doi.org/10.4161/gmic.22973
14. 14. Russo A.F. (2017). Overview of neuropeptides: awakening the senses?. Headache, 57 Suppl 2(Suppl 2): 37–46. Https://doi.org/10.1111/head.13084
15. 15. Foster, J.A., Baker, G.B. ve Dursun, S.M. (2021). The relationship between the gut microbiome-immune system-brain axis and major depressive disorder. Front. Neurol, (12)721126. Https://doi.org/10.3389/fneur.2021.721126
16. 16. Rutsch, A., Kantsjö, J.B. ve Ronchi, F. (2020). The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology. Front. Immunol., (11) 604179. Https://doi.org/10.3389/fimmu.2020.604179
17. 17. Tan, H-E. (2023). The microbiota-gut-brain axis in stress and depression. Front. Neurosci. (17)1151478. Https://doi.org/10.3389/fnins.2023.1151478
18. 18. Liu, G., Yu, Q., Tan, B., Ke, X., Zhang, C., Li, H… Lu, Y. (2022). Gut dysbiosis impairs hippocampal plasticity and behaviors by remodeling serum metabolome. Gut Microbes, 14(1). Https://doi.org/10.1080/19490976.2022.2104089
19. 19. Ertal, E. ve Özkaya, V. (2022). Düşük veya yüksek karbonhidratlı diyetlerin beyin, beyin-bağırsak aksı ve bilişsel işlevler üzerine etkisi. IGUSABDER, 18: 1070-1083. Https://doi.org/10.38079/igusabder.1140592
20. 20. Kalip, K. ve Atak, N. (2018). Bağırsak mikrobiyotası ve sağlık. Turk J Public Health, (16)1: 58-73.
21. 21. Cersosimoa, M.G. ve Benarrochb, E.E. (2012). Autonomic involvement in parkinson's disease: pathology, pathophysiology, clinical features and possible peripheral biomarkers. Journal of the Neurological Sciences, 313(1): 57-63. Https://doi.org/10.1016/j.jns.2011.09.030
22. 22. Lees, A.J., Hardy, J. Ve Revesz, T. (2009). Parkinson's disease. The Lancet, 373(9680): 2055-2066. Https://doi.org/10.1016/S0140-6736(09)60492-X
23. 23. Akbayır, E., Şen, M., Ay, U., Şenyer, S., Tüzün, E., Küçükali, C.İ. (2017). Parkinson hastalığının etyopatogenezi. Deneysel Tıp Dergisi, 7(13): 1-23.
24. 24. Durmuş, H., Gokalp, M.A., Hanagasi, H.A. (2015). Prevalence of Parkinson’s disease in Baskale, Turkey: a population based study. Neurol Sci, 36: 411-413. https://doi.org/10.1007/s10072-014-1988-x
25. 25. Dursun, B. (2008). Otozomal resesif geçişli parkinson hastalığında parkin (PARK2) geni mutasyonlarının araştırılması. Yüksek Lisans Tezi, Tez no: 203945.
26. 26. Gatto, N. M., Rhodes, S. L., Manthripragada, A. D., Bronstein, J., Cockburn, M., Farrer, M., & Ritz, B. (2010). α-Synuclein gene may interact with environmental factors in increasing risk of Parkinson's disease. Neuroepidemiology, 35(3), 191–195. https://doi.org/10.1159/000315157
27. 27. Chin-Chan, M., Navarro-Yepes, J., & Quintanilla-Vega, B. (2015). Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Frontiers in cellular neuroscience, 9: 124. https://doi.org/10.3389/fncel.2015.00124
28. 28. Cersosimo, M.G., Raina, G.B., Pecci, C., Pellene, A., Calandra, C.R., Gutiérrez, C., Micheli, F.E., Benarroch E.E. (2013). Gastrointestinal manifestations in parkinson’s disease: prevalence and occurrence before motor symptoms. J Neurol 260, 1332–1338. Https://doi.org/10.1007/s00415-012-6801-2
29. 29. Mulak A. Ve Bonaz B. (2015). Brain-gut-microbiota axis in parkinson's disease. World J Gastroenterol, 21(37): 10609-10620. Https://dx.doi.org/10.3748/wjg.v21.i37.10609
30. 30. Sharma, S.R., Gonda, X. ve Tarazi, F.I. (2018). Autism spectrum disorder: classification, diagnosis and therapy. Pharmacology and Therapeutics, 190: 91-104. https://doi.org/10.1016/j.pharmthera.2018.05.007
31. 31. Finegold, S.M., Dowd, S.E., Gontcharova, V., Liu, C., Henley, K.E., Wolcott, R.D…. Green III, J.A. (2010). Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe, 16: 444-453. https://doi.org/10.1016/j.anaerobe.2010.06.008
32. 32. Yosunkaya, E. (2013). Otizm etyolojisinde genetik ve güncel perspektif. İst Tıp Fak Derg., 76(4): 84-88.
33. 33. Yazıcı, İ.P. (2020). Otizm spektrum bozukluğu tanılı olgularda prenatal ve perinatal özelliklerin değerlendirilmesi: cinsiyet farklılığı var mı?. Turk J Child Adolesc Ment Health, 27(3): 187-195. https://doi.org/10.4274/tjcamh.galenos.2020.46220
34. 34. Karakoç Demirkaya, S. (2019). Otizm neden artışta? Klinik Psikiyatri, 22: 123-124. https://doi.org/10.5505/kpd.2019.84755
35. 35. Sherwin, E., Sandhu, K.V., Dinan, T.G. ve Cryan, J.F. (2016). May the force be with you: the light and dark sides of the microbiota–gut–brain axis in neuropsychiatry. CNS Drugs 30: 1019-1041. https://doi.org/10.1007/s40263-016-0370-3
36. 36. Parracho, H.M.R.T., Bingham, M.O., Gibson, G.R. ve McCartney, A.L. (2005). Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. Journal of Medical Microbiology, 54: 987-991. https://doi.org/10.1099/jmm.0.46101-0
37. 37. Finegold, S.M., Downes, J. ve Summanen, P.H. (2012). Microbiology of regressive autism. Anaerobe, 18(2): 260-262. https://doi.org/10.1016/j.anaerobe.2011.12.018
38. 38. Schaffer, S., Asseburg, H., Kuntz, S., Muller, W.E. ve Eckert, G.P. (2012). Effects of polyphenols on brain ageing and alzheimer’s disease: focus on mitochondria. Mol Neurobiol 46, 161-178 https://doi.org/10.1007/s12035-012-8282-9
39. 39. Yıldırım, N. ve Can Eke B. (2024). Alzheımer hastalığı, risk faktörleri ve tedavi. Ankara Ecz. Fak. Derg., 48(2): 766-790. https://doi.org/10.33483/jfpau.1441827
40. 40. Langa, K. M., Larson, E. B., Crimmins, E. M., Faul, J. D., Levine, D. A., Kabeto, M. U., & Weir, D. R. (2017). A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012. JAMA internal medicine, 177(1), 51–58. https://doi.org/10.1001/jamainternmed.2016.6807
41. 41. Semercioğlu, B. (2022). Alzheimer Hastalığı ve Oral Mikrobiyota. J Health Sci Clin Res., 1(1): 48-55.
42. 42. Rogers, G.B., Keating, D.J., Young, R.L., Wong, M.L., Licinio, J. ve Wesselingh, S. (2016). From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Molecular Psychiatry, 21: 738-748. https://doi.org/10.1038/mp.2016.50
43. 43. Marizzoni, M., Provasi, S., Cattaneo, A. ve Frisoni, G.B. (2017). Microbiota and neurodegenerative diseases. Current Opinion in Neurology 30(6): 630-638. https://doi.org/10.1097/WCO.0000000000000496
44. 44. Bonfili, L., Cecarini, V., Berardi, S., Scarpona S., Suchodolski, J.S., Nasuti, C…. Eleuteri, A.M. (2017). Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Scientific Reports, 7: 2426. https://doi.org/10.1038/s41598-017-02587-2
45. 45. Baydan, T. ve Karaca Sivrikaya, S. (2021). Multiple Skleroz ve Mikrobiyata. Balıkesir Sağlık Bilimleri Dergisi, 10(3):410-415. https://doi.org/10.53424/balikesirsbd.882071
46. 46. Katsara, M. ve Apostolopoulos, V. (2018). Editorial: Multiple Sclerosis: Pathogenesis and Therapeutics. Journal of Medicinal Chemistry, 14(2), 104-105. http://doi.org/10.2174/157340641402180206092504
47. 47. Öztürk, S., Aytaç, G., Kızılay, F. ve Sindel, M. (2016). Multipl skleroz. Akdeniz Tıp Dergisi, 3: 137-147. https://doi.org/10.17954/amj.2017.86
48. 48. Bulut, S., Kılıç, H. ve Demir, C.F. (2011). Yukarı fırat bölgesinde multipl skleroz tanısı ile izlenen hastaların klinik ve demografik özellikleri. Fırat Tıp Dergisi, 16(2): 84-90.
49. 49. Odenwald, M. A., & Turner, J. R. (2017). The intestinal epithelial barrier: a therapeutic target? Nature Reviews Gastroenterology & Hepatology, 14(1), 9-21. http://doi.org/10.1038/nrgastro.2016.169
50. 50. Berer, K., Gerdes, L.A., Cekanaviciute, E., Jia, X., Xiao, L., Xia, Z…. Wekerle, H. (2017). Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A., 114(40):10719–10724. Https://doi.org/10.1073/pnas.1711233114
51. 51. Cekanaviciute, E., Yoo, B.B., Runia, T.F., Debelius, J.W., Singh, S., Nelson, C.A…. Baranzini, S.E. (2017). Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A. 114(40):10713–10718. Https://doi.org/10.1073/pnas.1711235114
52. 52. Wu, J., Zhang, Y., Yang, H., Rao, Y., Miao, J., ve Lu, X. (2016). Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy. The Canadian journal of infectious diseases and medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale, 9032809. https://doi.org/10.1155/2016/9032809
53. 53. Günbey, C. ve Turanlı, G. (2022). Epilepsi ve pediatrik epilepsi sendromları. Türkiye Çocuk Hastalıkları Dergisi, 16: 249-257. https://doi.org/10.12956/tchd.888121
54. 54. Şafak, B., Altunan, B., Topçu, B. ve Eren Topkaya, A. (2020). The gut microbiome in epilepsy. Microbial Pathogenesis 139. https://doi.org/10.1016/j.micpath.2019.103853
55. 55. De Zwart, P.L., Jeronimus, BF. ve De Jonge, P. (2018). Empirical evidence for definitions of episode, remission, recovery, relapse and recurrence in depression: a systematic review. Epidemiol Psychiatr Sci. 28(5):544–562. https://doi.org/10.1017/S2045796018000227
56. 56. Kafes, A. Y. (2021). Depresyon ve anksiyete bozuklukları üzerine bir bakış. Humanistic Perspective, 3 (1): 186-194. https://doi.org/10.47793/hp.867111
57. 57. Yıldız, N.G., Aydın, K., Aydın, H.Z., Phırı, Y.V.A., Yıldız, H. (2024). Türkiye’de depresyonun yaygınlığı ile ilişkili faktörler: nüfusa dayalı bir çalışma. Türk Psikiyatri Dergisi, 35(3):167−177. https://doi.org/10.5080/u27179
58. 58. Helvacı Çelik, F., ve Hocaoğlu, Ç. (2016). Major Depresif Bozukluk’ Tanımı, Etyolojisi ve Epidemiyolojisi: Bir Gözden Geçirme. Çağdaş Tıp Dergisi, 6(1), 51-66. https://doi.org/10.16899/ctd.03180
59. 59. Albayrak, E.Ö. ve Ceylan, M.E. (2004). Depresyon etiyolojisinde nörobiyolojik etkenler. Düşünen Adam, 17(1): 27-33.
60. 60. Jiang, H., Ling, Z., Zhang, Y., Mao, H., Ma, Z., Yin, Y…. Ruan, B. (2015). Altered fecal microbiota composition in patients with major depressive disorder. Brain, Behavior and Immunity, 48: 186-194. https://doi.org/10.1016/j.bbi.2015.03.016
61. 61. Sherwin, E., Rea, K., Dinan, T.G. ve Cryan, J.F. (2016). A gut (microbiome) feeling about the brain. Current Opinion in Gastroenterology, 32(2): 96-102. https://doi.org/10.1097/MOG.0000000000000244
62. 62. Aizawa, E., Tsuji, H., Asahara, T., Takahashi, T., Teraişi, T., Yoşida, S…. Kunugi, H. (2016). Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. Journal of Affective Disorders, 202: 254-257. https://doi.org/10.1016/j.jad.2016.05.038
63. 63. Steenbergen, L., Sellaro, R., Van Hemert, S., Bosch, J.A., Colzato, L.S. (2015). A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain, Behavior and Immunity, 48: 258-264. https://doi.org/10.1016/j.bbi.2015.04.003
64. 64. Messaoudi, M., Lalonde, R., Violle, N., Javelot, H., Desor, D., Nejdi, A…. Cazaubiel, J.M. (2010). Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. British Journal of Nutrition, 105: 755–764. https://doi.org/10.1017/S0007114510004319
65. 65. Karamustafalıoğlu, O. ve Yumrukçal, H. (2011). Depresyon ve anksiyete bozuklukları. Şişli Etfal Hastanesi Tıp Bülteni, 45(2): 65- 74.
66. 66. Topçuoğlu, V. (2022). Anksiyete bozuklukları. Istanbul Kent University J Health Sciences, 1(1): 38-40.
67. 67. Ionescu, D.F., Niciu, M.J., Mathews, D.C., Richards, E.M. ve Zarate Jr, C.A. (2014). Neurobiology of Anxious Depression: A Review. Depression and anxiety, 30(4): 374–385. https://doi.org/10.1002/da.22095
68. 68. O’Mahony, S.M., Marchesi, J.R., Scully, P., Codling, C., Ceolho, A.M., Quigley, E.M.M…. Dinan, T.G. (2009). Early life stress alters behavior, ımmunity, and microbiota in rats: ımplications for ırritable bowel syndrome and psychiatric ıllnesses. Biological Psychiatry, 65(3): 263–267. https://doi.org/10.1016/j.biopsych.2008.06.026
69. 69. Yi-huan, C., Jie, B., Di, W., Shou-fen, Y., Xiao-ling, Q., Hua, B., Hua-ning, W., Zheng-wu, P. (2019). Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response. Journal of Affective Disorders, 259: 56-66. https://doi.org/10.1016/j.jad.2019.08.014
70. 70. Weber, B. C., Manfredo, H. N., ve Rinaman, L. (2009). A potential gastrointestinal link between enhanced postnatal maternal care and reduced anxiety-like behavior in adolescent rats. Behavioral neuroscience, 123(6), 1178–1184. https://doi.org/10.1037/a0017659
71. 71. Lach, G., Schellekens, H., Dinan, T.G. ve Cryan, J.F. (2017). Anxiety, depression, and the microbiome: a role for gut peptides. Neurotherapeutics, 15(1): 36–59. https://doi.org/10.1007/s13311-017-0585-0
72. 72. Morys, J., Małecki, A. ve Nowacka-Chmielewska, M. (2024). Stress and the gut-brain axis: an inflammatory perspective. Front. Mol. Neurosci. 17:1415567. https://doi.org/10.3389/fnmol.2024.1415567
73. 73. Jiang, M., Kang, L., Wang, Y.L., Zhou, B., Li, H.Y., Yan, Q. ve Liu, Z.G. (2024). Mechanisms of microbiota-gut-brain axis communication in anxiety disorders. Front. Neurosci, 18:1501134. https://doi.org/10.3389/fnins.2024.1501134
74. 74. Kocal, Y., Karakuş, G. ve Sert, D. (2017). Şizofreni: etyoloji, klinik özellikler ve tedavi. Arşiv Kaynak Tarama Dergisi, 26(2): 251-267. https://doi.org/10.17827/aktd.303574
75. 75. Binbay, T., Ulaş, H., Elbi, H. ve Alptekin, K. (2011). Türkiye’de psikoz epidemiyolojisi: yaygınlık tahminleri ve başvuru oranları üzerine sistematik bir gözden geçirme. Türk Psikiyatri Dergisi, 22(1): 40-52. https://doi.org/10.5080/u6244
76. 76. Taşkın Uyan, T., Köroğlu, A. ve Hocaoğlu, Ç. (2023). Şizofreni: etiyoloji, tanı ve tedavi yaklaşımlarında güncel durum. ERÜ Sağlık Bilimleri Fakültesi Dergisi, 10(1): 19-35.
77. 77. Nehme, R., Pietiläinen, O., Artomov, M., Tegtmeyer, M., Valakh, V., Lehtonen, L…. Eggan, K. (2022). The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia. Nature Communications, 13: 3690. https://doi.org/10.1038/s41467-022-31436-8
78. 78. Cannon, M., Jones, P.B. ve Murray, R.M. (2002). Obstetric complications and schizophrenia: historical and meta-analytic review. American Journal of Psychiatry 159(7): 1080-1092. https://doi.org/10.1176/appi.ajp.159.7.1080
79. 79. Crawford, P. ve Go, K. V. (2022). Schizophrenia. American Family Physician, 106(4): 388-396.
80. 80. Castro-Nallar, E., Bendall, M. L., Pérez-Losada, M., Sabuncyan, S., Severance, E. G., Dickerson, F. B., Schroeder, J. R., Yolken, R. H., ve Crandall, K. A. (2015). Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls. PeerJ, 3: e1140. https://doi.org/10.7717/peerj.1140
81. 81. Nemani, K., Ghomi, R.H., McCormick, B. ve Fan, X. (2014). Schizophrenia and the gut–brain axis. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 56: 155-160. https://doi.org/10.1016/j.pnpbp.2014.08.018
82. 82. Kartalcı, Ş. 2018. Şizofreni etyolojisinde mikrobiyotanın rolü. Psikiyatride Güncel Yaklaşımlar, 10(2): 265-278. https://doi.org/10.18863/pgy.358105
83. 83. Jain A, Mitra P. Bipolar Disorder. [Updated 2023 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: 04.01.2025 https://www.ncbi.nlm.nih.gov/books/NBK558998/
84. 84. Charney, A. W., Ruderfer, D. M., Stahl, E. A., Moran, J. L., Chambert, K., Belliveau, R. A., Forty, L., Gordon-Smith, K., Di Florio, A., Lee, P. H., Bromet, E. J., Buckley, P. F., Escamilla, M. A., Fanous, A. H., Fochtmann, L. J., Lehrer, D. S., Malaspina, D., Marder, S. R., Morley, C. P., Nicolini, H., … Sklar, P. (2017). Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder. Translational psychiatry, 7(1): e993. https://doi.org/10.1038/tp.2016.242
85. 85. Binbay, T., Alptekin, K., Elbi, H., Zağlı, N., Drukker, M., Aksu Tanık, F…. Van Os, J. (2012). İzmir kent merkezinde şizofreni ve psikotik belirtili bozuklukların yaşamboyu yaygınlığı ve ilişkili oldukları sosyodemografik özellikler. Türk Psikiyatri Dergisi, 23(3): 149-160.
86. 86. Miklowitz, D. J., & Johnson, S. L. (2006). The psychopathology and treatment of bipolar disorder. Annual review of clinical psychology, 2: 199-235. https://doi.org/10.1146/annurev.clinpsy.2.022305.095332
87. 87. Ching, C. R. K., Hibar, D. P., Gurholt, T. P., Nunes, A., Thomopoulos, S. I., Abé, C., Agartz, I., Brouwer, R. M., Cannon, D. M., de Zwarte, S. M. C., Eyler, L. T., Favre, P., Hajek, T., Haukvik, U. K., Houenou, J., Landén, M., Lett, T. A., McDonald, C., Nabulsi, L., Patel, Y., … ENIGMA Bipolar Disorder Working Group (2022). What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group. Human brain mapping, 43(1): 56–82. https://doi.org/10.1002/hbm.25098
88. 88. Evans, S.J., Bassis, C.M., Hein, R., Assari, S., Flowers, S.A., Kelly, M.B…. McInnis, M.G. (2017). The gut microbiome composition associates with bipolar disorder and illness severity. Journal of Psychiatric Research, 87: 23-29. https://doi.org/10.1016/j.jpsychires.2016.12.007
89. 89. McIntyre, R.S., Subramaniapillai, M., Shekotikhina, M., Carmona, N.E., Lee, Y., Mansur, R.B…. Surette, M.G. (2019). Characterizing the gut microbiota in adults with bipolar disorder: a pilot study. Nutritional Neuroscience, 24(3): 173-180. https://doi.org/10.1080/1028415X.2019.1612555
90. 90. Gondalia, S., Parkinson, L., Stough, C. ve Scholey, A. (2019). Gut microbiota and bipolar disorder: a review of mechanisms and potential targets for adjunctive therapy. Psychopharmacology, 236: 1433–1443. https://doi.org/10.1007/s00213-019-05248-6
91. 91. Zhao, J., Liu, J., Feng, J., Liu, X. ve Hu, Q. (2024). The gut microbiota-brain connection: insights into major depressive disorder and bipolar disorder. Frontiers in Psychiatry, 15: 1421490. https://doi.org/10.3389/fpsyt.2024.1421490
92. 92. Obi-Azuike, C., Ebiai, R., Gibson, T., Hernandez, A., Khan, A., Anugwom, G…. Oladunjoye, F. (2023). A systematic review on gut–brain axis aberrations in bipolar disorder and methods of balancing the gut microbiota. Brain and Behavior, 13(6): e3037. https://doi.org/10.1002/brb3.3037
93. 93. Dickerson, F., Adamos, M., Katsafanas, E., Khushalani, S., Origoni, A., Savage, C…. Yolken, R.H. (2018). Adjunctive probiotic microorganisms to prevent rehospitalization in patients with acute mania: A randomized controlled trial. Bipolar Disorders, 20(7): 614-621. https://doi.org/10.1111/bdi.12652
94. 94. Hinton R. (2020). A case report looking at the effects of faecal microbiota transplantation in a patient with bipolar disorder. The Australian and New Zealand Journal of Psychiatry, 54(6): 649–650. https://doi.org/10.1177/0004867420912834
95. 95. Onaran Acar, B. ve Kanca, N. (2022). Psikobiyotikler: depresyon ve anksiyete ile ilişkisi. Sağlık Bilimleri Dergisi (Journal of Health Sciences), 31(1): 101-106. https://doi.org/10.34108/eujhs.827227
96. 96. Fond, G., Boukouaci, W., Chevalier, G., Regnault, A., Eberl, G., Hamdani, N…. Leboyer, M. (2015). The “psychomicrobiotic”: Targeting microbiota in major psychiatric disorders: A systematic review. Pathologie Biologie, 63(1): 35-42. https://doi.org/10.1016/j.patbio.2014.10.003