Obsesif Kompulsif Bozukluk ve Bağırsak Mikrobiyotası
Özet
Obsesif-kompulsif bozukluk (OKB), tekrarlayan rahatsız edici düşünceler ve sıkıntıyı azaltmaya yönelik ritüelistik davranışlar ile karakterize, toplumda yaşam boyu prevalansı %2-3 olan ve yüksek sakatlık riski taşıyan önemli bir psikiyatrik rahatsızlıktır. Mevcut farmakolojik tedavilere verilen düşük yanıt oranları, hastalığın etiyolojisinde serotonin ve dopamin dışındaki ek yolların araştırılmasını gerekli kılmış ve bu bağlamda mikrobiyota-bağırsak-beyin (MGB) ekseni öne çıkmıştır. Merkezi sinir sistemi ile gastrointestinal sistem arasındaki bu çift yönlü iletişim; bağışıklık ve enflamasyon süreçleri, HPA ekseni hiperaktivitesi, nörotransmiter regülasyonu ve vagus siniri iletimi mekanizmaları üzerinden gerçekleşmektedir. Yapılan çalışmalarda, OKB hastalarında bağırsak mikrobiyotasının alfa çeşitliliğinin sağlıklı kontrollere göre anlamlı derecede düşük olduğu, stres faktörlerinin disbiyoza yol açtığı ve sızdıran bağırsak sendromu aracılığıyla proinflamatuar sitokin seviyelerini artırarak nöroenflamasyonu tetiklediği bulunmuştur. Ayrıca, bağırsaktaki bazı bakteri suşlarının GABA ve triptofan gibi kritik nörotransmiterleri üretme yeteneği olduğu saptanmıştır. Bu doğrultuda, mikrobiyotayı modüle etmeye yönelik SSRI tedavileri, florayı düzenleyen minosiklin gibi antibiyotikler ve OKB benzeri davranışları hafifleten probiyotik takviyeleri yeni tedavi alternatifleri sunmaktadır. Henüz kısıtlı olan bu literatürün insan odaklı klinik çalışmalarla genişletilmesi, OKB tedavisinde devrimsel bir katalizör işlevi görebilir.
Obsessive-compulsive disorder (OCD) is a significant psychiatric condition characterized by recurrent intrusive thoughts and ritualistic behaviors aimed at reducing distress, with a lifetime prevalence of 2-3% in society and a high risk of disability. Low response rates to current pharmacological treatments have necessitated the investigation of additional etiological pathways beyond serotonin and dopamine, highlighting the microbiota-gut-brain (MGB) axis. This bidirectional communication between the central nervous system and the gastrointestinal tract operates through immune and inflammatory processes, HPA axis hyperactivity, neurotransmitter regulation, and vagus nerve transmission. Studies have shown that the alpha diversity of the gut microbiota in OCD patients is significantly lower than in healthy controls, that stressors induce dysbiosis, and that it triggers neuroinflammation by increasing proinflammatory cytokine levels via the leaky gut mechanism. Furthermore, certain bacterial strains in the gut have been found capable of producing critical neurotransmitters like GABA and tryptophan. Accordingly, SSRI treatments modifying the microbiota, antibiotics like minocycline regulating the flora, and probiotic supplements alleviating OCD-like behaviors offer new therapeutic alternatives. Expanding this currently limited literature with human-focused clinical trials could serve as a revolutionary catalyst in OCD treatment.
Referanslar
Kugler BB, Lewin AB, Phares V, et al. Quality of life in obsessive-compulsive disorder: The role of mediating variables. Psychiatry Research . 2013;206(1):43–49.
Foster JA, McVey Neufeld KA. Gut-brain axis: How the microbiome influences anxiety and depression.Trends in Neurosciences. 2013;36(5):305–312.
Vuong HE, Hsiao EY. Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder.Biological Psychiatry. 2017;81(5):411–423.
Evans SJ, Bassis CM, Hein R, et al. The gut microbiome composition associates with bipolar disorder and illness severity. Journal of Psychiaticr Research . 2017;87:23–29.
Aarts E, Ederveen THA, Naaijen J, et al. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One. 2017;12(9).
Schwarz E, Maukonen J, Hyytiäinen T, et al. Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response. Schizophrenia research. 2018;192:398–403.
Quagliariello A, Del Chierico F, Russo A, et al. Gut microbiota profiling and gut-brain crosstalk in children affected by pediatric acute-onset neuropsychiatric syndrome and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Frontiers in Microbiology. 2018;9:675
Turna J, Grosman Kaplan K, Anglin R, et al. The gut microbiome and inflammation in obsessive-compulsive disorder patients compared to age- and sex-matched controls: a pilot study. Acta Psychiatrica Scandinavica. 2020;142(4):337–347.
Messaoudi M, Violle N, Bisson JF, et al. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes . 2011;2(4):256-261.
Kantak PA, Bobrow DN, Nyby JG. Obsessive-compulsive-like behaviors in house mice are attenuated by a probiotic (Lactobacillus rhamnosus GG). Behavioural Pharmacology. 2014;25(1):71–79.
Turna J, Grosman Kaplan K, Anglin R, et al. “wHAT’S BUGGING the GUT in OCD?” A REVIEW of the GUT MICROBIOME in OBSESSIVE-COMPULSIVE DISORDER.Depression and Anxiety. 2016;33(3):171–178.
Rao NP, Venkatasubramanian G, Ravi V, et al.Plasma cytokine abnormalities in drug-naïve, comorbidity-free obsessive-compulsive disorder. Psychiatry Research. 2015;229(3):949–952.
Ekinci A, Dergisi OE-AP, 2017 undefined. The relationships between low grade inflammation, demographic and clinical characteristics in patients with OCD. Anadolu Psikiyatri Dergisi. 2017;18(5):438–445.
Cryan JF, O’riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiological Reviews. 2019;99(4):1877–2013.
Turna J, Grosman Kaplan K, Patterson B, et al. Higher prevalence of irritable bowel syndrome and greater gastrointestinal symptoms in obsessive-compulsive disorder. Journal of Psychiatric Research. 2019;118:1–6.
Özyürek M, Özcan T.Mechanisms of psychobiotic effect and gut microbiota. International Journal of Science, Technology and Design.2020;(1).
Barzilay R, Patrick A, Calkins ME,et al. Association between early-life trauma and obsessive compulsive symptoms in community youth. Depression and Anxiety. 2019;36(7):586–595.
Michels N, Van de Wiele T, Fouhy F, et al.Gut microbiome patterns depending on children’s psychosocial stress: Reports versus biomarkers. Brain Behaviour and Immunity. 2019;80:751–762.
Siopi E, Chevalier G, Katsimpardi L, et al. Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine. Cell Reports. 2020;30(11):3682-3690.
Sinopoli VM, Burton CL, Kronenberg S, et al.A review of the role of serotonin system genes in obsessive-compulsive disorder.Neuroscience and Biobehavioral Reviews. 2017;80:372–381.
Turna J, Grosman Kaplan K, Anglin R, et al. The gut microbiome and inflammation in obsessive-compulsive disorder patients compared to age- and sex-matched controls: a pilot study. Acta Psychiatrica Scandinavica. 2020;142(4):337–347.
Umesaki Y, Okada Y, Matsumoto S, et al.Segmented Filamentous Bacteria Are Indigenous Intestinal Bacteria That Activate Intraepithelial Lymphocytes and Induce MHC Class II Molecules and Fucosyl Asialo GM1 Glycolipids on the Small Intestinal Epithelial Cells in the Ex-Germ-Free Mouse. Microbiology and immunology. 1995;39(8):555–562.
Kamada N, Seo SU, Chen GY, et al. Role of the gut microbiota in immunity and inflammatory disease .Nature Reviews Immunology. 2013;13(5):321–335.
Kamada N, Núñez G. Regulation of the immune system by the resident intestinal bacteria. Gastroenterology. 2014;146(6):1477–1488.
Fineberg NA, Reghunandanan S, Brown A, et al.Pharmacotherapy of obsessive-compulsive disorder: Evidence-based treatment and beyond. Australian and New Zealand Journal of Psychiatry. 2013;47(2):121–141.
Altemus M, Pigott T, Kalogeras KT, et al. Abnormalities in the Regulation of Vasopressin and Corticotropin Releasing Factor Secretion in Obsessive-Compulsive Disorder. Archives of General Psychiatry. 1992;49(1):9–20.
Lindsay JR, Nieman LK. The hypothalamic-pituitary-adrenal axis in pregnancy: Challenges in disease detection and treatment.Endocrine Reviews. 2005;26(6):775–799.
Maina G, Albert U, Bogetto F,et al. Recent life events and obsessive-compulsive disorder (OCD): The role of pregnancy/delivery. Psychiatry Research. 1999;89(1):49–58.
Forray A, Focseneanu M, Pittman B, et al. Onset and exacerbation of obsessive-compulsive disorder in pregnancy and the postpartum period.The Journal of Clinical Psychiatry. 2010;71(8):1061–1068.
Frodl T, O’Keane V. How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans .Neurobiology of Disease. 2013;52:24–37.
Rosso G, Albert U, Asinari GF, et al. Stressful life events and obsessive-compulsive disorder: Clinical features and symptom dimensions. Psychiatry Research. 2012;197(3):259–264.
Zimomra ZR, Porterfield VM, Camp RM, et al.Time-dependent mediators of HPA axis activation following live Escherichia coli. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2011;301(6):1648–1657.
Dinan TG, Cryan JF. Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology.Psychoneuroendocrinology. 2012;37(9):1369–1378.
Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics. BioEssays. 2011;33(8):574–581.
Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice.The Journal of Physiology. 2004;558(1):263–275.
Maes M, Twisk FNM, Kubera M, et al.Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome. Journal of Affective Disorder . 2012;136(3):909–917.
Qin L, Wu X, Block ML, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007;55(5):453–462.
Severance EG, Gressitt KL, Stallings CR, et al. Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia. Schizophrenia Research. 2013;148(1–3):130–137.
Savignac HM, Kiely B, Dinan TG, et al. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil. 2014;26(11):1615–1627.
Collins SM, SuretteM,Bercik P. The interplay between the intestinal microbiota and the brain. Nature Reviews Microbiology.2012;10(11):735-742
Desbonnet L, Garrett L, Clarke G,et al. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. Journal of Psychiatric Research. 2008;43(2):164–74.
Russo I, Luciani A, de Cicco P, et al. Butyrate attenuates lipopolysaccharide-induced inflammation in intestinal cells and Crohn’s mucosa through modulation of antioxidant defense machinery. PLoS ONE. 2012;7(3): e32841.
Rivière A, Selak M, Lantin D,et al. Bifidobacteria and butyrate-producing colon bacteria: Importance and strategies for their stimulation in the human gut.Frontiers in Microbiology.2016;7:979.
Huuskonen J, Suuronen T, Nuutinen T, et al.Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids. British Journal of Pharmacology. 2004;141(5):874–880.
Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice. Science Translational Medicine. 2014; 6(263): 263ra158-263ra158.
Sherry CL, Kim SS, Dilger RN, et al. Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization. Brain Behaviour and Immunity. 2010;24(4):631–640.
Turna J, Grosman Kaplan K, Anglin R, et al. The gut microbiome and inflammation in obsessive-compulsive disorder patients compared to age- and sex-matched controls: a pilot study. Acta Psychiatrica Scandinavica. 2020;142(4):337–47.
Thayer JF, Sternberg EM. Neural concomitants of immunity-Focus on the vagus nerve .Neuroimage. 2009;47(3):908–910.
Bercik P, Park AJ, Sinclair D, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterology & Motility. 2011;23(12):1132–1139.
Bravo JA, Forsythe P, Chew MV, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences . 2011;108(38):16050–16055.
Jackson MA, Verdi S, Maxan ME, et al. Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nature communications. 2018;9(1):1-8.
Sun L, Zhang H, Cao Y, et al. Fluoxetine ameliorates dysbiosis in a depression model induced by chronic unpredicted mild stress in mice. International journal of medical sciences. 2019;16(9):1260–1270.
Farhood Z, Ong AA, Discolo CM. PANDAS: A systematic review of treatment options. International journal of pediatric otorhinolaryngology. 2016;89:149–153.
Esalatmanesh S, Abrishami Z, Zeinoddini A, et al. Minocycline combination therapy with fluvoxamine in moderate-to-severe obsessive–compulsive disorder: A placebo-controlled, double-blind, randomized trial. Psychiatry and clinical neurosciences. 2016;70(11):517–526.
Rodriguez CI, Bender J, Marcus SM, et al. Minocycline augmentation of pharmacotherapy in obsessive-compulsive disorder: An open-label trial. Journal of Clinical Psychiatry. 2010;71(9):1247–1249.
Ritchie ML, Romanuk TN. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLoS One. 2012;7(4):e34938.
Dinan TG, Cryan JF. Melancholic microbes: A link between gut microbiota and depression? Neurogastroenterology & Motility. 2013;25(9):713–719.
