Microbiota intestinal y su relación con la depresión
Resumen
La depresión es una de las enfermedades de salud mental más prevalentes en el mundo, con un impacto significativo en la calidad de vida de quienes la padecen. En los últimos años, el eje microbiota-intestino-cerebro (EMIC) ha adquirido una relevancia creciente al tratarse de una conexión bidireccional entre el sistema gastrointestinal y el sistema nervioso central. La disbiosis intestinal, resultado de un desequilibrio en la microbiota, puede alterar la producción de neurotransmisores clave como serotonina, dopamina y GABA, lo que contribuye a la inflamación sistémica, disfunción de barreras biológicas y, en última instancia, al desarrollo o exacerbación de estados depresivos. Factores como el estrés y el estilo de vida también juegan un papel crucial en esta interacción, intensificando sus efectos negativos en la salud mental. Terapias como el uso de probióticos, prebióticos, modificaciones dietéticas y el trasplante de microbiota fecal han surgido como posibles intervenciones para abordar este problema. Sin embargo, se necesita mayor evidencia científica para validar su eficacia clínica. Este artículo tiene como objetivo analizar las interacciones entre la microbiota intestinal y los neurotransmisores involucrados en la depresión, a través de la revisión de la literatura, explorando nuevas perspectivas para abordar la depresión desde un enfoque holístico.
Descargas
Referencias
1. World Health Organization WHO. Depressive disorder (depression). Depression. Disponible en: https://www.who.int/news-room/fact-sheets/detail/depression
2. University of Washington. Institute for Health Metrics and Evaluation [Internet]. Disponible en: https://vizhub.healthdata.org/gbd-results/
3. Hermann H. Time for united action on depression: a Lancet-World Psychiatric Association Commission. Lancet. 2022; 399(10328):957-1022. DOI: 10.1016/S0140-6736(21)02141-3
4. Jain S, Gupta S, Li VW, Suthoff E, Arnaud A. BMC Psychiatry. 2022; 22(1):542. DOI: 10.1186/s12888-022-04165-x
5. Ministerio de Salud y Protección Social-Colciencias. Guía de Práctica Clínica Detección temprana y diagnóstico del episodio depresivo y trastorno depresivo recurrente en adultos. Atención integral de los adultos con diagnóstico de episodio depresivo o trastorno depresivo recurrente. Ministerio de Salud y Protección Social - ColcienciasCentro Nacional de Investigación en Evidencia y Tecnologías en Salud CINETS; 2013. (22). Disponible en: https://www.minsalud.gov. co/sites/rid/Lists/BibliotecaDigital/RIDE/INEC/IETS/GPC_Comple_ Depre%20(1).pdf
6. Chesney E, Goodwin GM, Fazel S. Risks of all-cause and suicide mortality in mental disorders: a meta-review. World Psychiatry. 2014; 13(2):153-60. DOI: 10.1002/wps.20128.
7. Foster JA, McVey Neufeld KA. Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013; 36(5):305-12. DOI: 10.1016/j.tins.2013.01.005
8. Alli SR, Gorbovskaya I, Liu JCW, Kolla NJ, Brown L, Müller DJ. The Gut Microbiome in Depression and Potential Benefit of Prebiotics, Probiotics and Synbiotics: A Systematic Review of Clinical Trials and Observational Studies. Int J Mol Sci. 2022; 23(9):4494. DOI: 10.3390/ijms23094494
9. Mohajeri MH, La Fata G, Steinert RE, Weber P. Relationship between the gut microbiome and brain function. Nutr Rev. 2018;76(7):481-496. DOI: 10.1093/nutrit/nuy009
10. Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019; 76(3):473-493. DOI: 10.1007/s00018-018-2943-4
11. Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-Bacterial Mutualism in the Human Intestine. Science. 2005; 307(5717):1915-20. DOI: 10.1126/science.1104816.
12. Mulak A. Brain-gut-microbiota axis in Parkinson’s disease. World J Gastroenterol. 2015; 21(37):10609-20. DOI: 10.3748/wjg.v21.i37.10609.
13. Schemann M, Neunlist M. The human enteric nervous system. Neurogastroenterol Motil. 2004; 16 Suppl 1:55-9. DOI: 10.1111/j.1743-3150.2004.00476.x.
14. Anlauf M, Schäfer MK ‐H., Eiden L, Weihe E. Chemical coding of the human gastrointestinal nervous system: Cholinergic, VIPergic, and catecholaminergic phenotypes. J Comp Neurol. 2003; 459(1):90-111. DOI: 10.1002/cne.10599.
15. Wong ML, Inserra A, Lewis MD, Mastronardi CA, Leong L, Choo J, et al. Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition. Mol Psychiatry. 2016; 21(6):797-805. DOI: 10.1038/mp.2016.46
16. Borre YE, O’Keeffe GW, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014; 20(9):509-18. DOI: 10.1016/j.molmed.2014.05.002
17. Bonaz B, Bazin T, Pellissier S. The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front Neurosci. 2018; 12:49. DOI: 10.3389/fnins.2018.00049
18. Winter G, Hart RA, Charlesworth RPG, Sharpley CF. Gut microbiome and depression: what we know and what we need to know. Rev Neurosci. 2018; 29(6):629-643. DOI: 10.1515/revneuro-2017-0072
19. Heintz-Buschart A, Wilmes P. Human Gut Microbiome: Function Matters. Trends Microbiol. 2018; 26(7):563-574. DOI: 10.1016/j.tim.2017.11.002
20. Shi N, Li N, Duan X, Niu H. Interaction between the gut microbiome and mucosal immune system. Mil Med Res. 2017 4:14. DOI: 10.1186/s40779-017-0122-9
21. 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
22. Medina-Rodriguez EM, Madorma D, O’Connor G, Mason BL, Han D, Deo SK, et al. Identification of a Signaling Mechanism by Which the Microbiome Regulates Th17 Cell-Mediated Depressive-Like Behaviors in Mice. Am J Psychiatry. 2020; 177(10):974-990. DOI: 10.1176/appi.ajp.2020.19090960
23. Liu L, Wang H, Chen X, Zhang Y, Zhang H, Xie P. Gut microbiota and its metabolites in depression: from pathogenesis to treatment. EBioMedicine. 2023; 90:104527. DOI: 10.1016/j.ebiom.2023.104527
24. Zhang Y, Fan Q, Hou Y, Zhang X, Yin Z, Cai X, et al. Bacteroides species differentially modulate depression-like behavior via gut-brain metabolic signaling. Brain Behav Immun. 2022; 102:11-22. DOI: 10.1016/j.bbi.2022.02.007
25. Chang L, Wei Y, Hashimoto K. Brain–gut–microbiota axis in depression: A historical overview and future directions. Brain Research Bulletin. mayo de 2022;182:44-56. Brain Res Bull. 2022; 182:44-56. DOI: 10.1016/j.brainresbull.2022.02.004
26. Ménard C, Hodes GE, Russo SJ. Pathogenesis of depression: Insights from human and rodent studies. Neuroscience. 2016; 3:321:138-162. DOI: 10.1016/j.neuroscience.2015.05.053
27. Hirschfeld RMA. History and Evolution of the Monoamine Hypothesis of Depression. J Clin Psychiatry. 2000; 61 Suppl 6:4-6.
28. Ma J, Wang R, Chen Y, Wang Z, Dong Y. 5-HT attenuates chronic stress-induced cognitive impairment in mice through intestinal flora disruption. J Neuroinflammation. 2023; 20(1):23. DOI: 10.1186/s12974-023-02693-1
29. Strandwitz P, Kim KH, Terekhova D, Liu JK, Sharma A, Levering J, et al. GABA-modulating bacteria of the human gut microbiota. Nat Microbiol. 2019; 4(3):396-403. DOI: 10.1038/s41564-018-0307-3
30. Cheng Y, Desse S, Martinez A, Worthen RJ, Jope RS, Beurel E. TNFα disrupts blood brain barrier integrity to maintain prolonged depressive-like behavior in mice. Brain Behav Immun. 2018; 69:556-567. DOI: 10.1016/j.bbi.2018.02.003
31. Zou L, Tian Y, Wang Y, Chen D, Lu X, Zeng Z, et al. High-cholesterol diet promotes depression- and anxiety-like behaviors in mice by impact gut microbe and neuroinflammation. J Affect Disord. 2023; 327:425-438. DOI: 10.1016/j.jad.2023.01.122
32. Bellono NW, Bayrer JR, Leitch DB, Castro J, Zhang C, O’Donnell TA, et al. Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways. Cell. 2017; 170(1):185-198.e16. DOI: 10.1016/j.cell.2017.05.034
33. Liu N, Sun S, Wang P, Sun Y, Hu Q, Wang X. The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine. IJMS. 2021; 22(15):7931. DOI: 10.3390/ijms22157931
34. Borodovitsyna O, Flamini M, Chandler D. Noradrenergic Modulation of Cognition in Health and Disease. Neural Plasticity. 2017; 2017:1-14. DOI: 10.1155/2017/6031478
35. McCutcheon RA, Abi-Dargham A, Howes OD. Schizophrenia, Dopamine and the Striatum: From Biology to Symptoms. Trends in Neurosciences. 2019; 42(3):205-20. DOI: 10.1016/j.tins.2018.12.004
36. Freestone PP, Williams PH, Haigh RD, Maggs AF, Neal CP, Lyte M. Growth Stimulation of Intestinal Commensal Escherichia coli by Catecholamines: A Possible Contributory Factor in Trauma-Induced Sepsis: Shock. 2002; 18(5):465-70. DOI: 10.1097/00024382-200211000-00014
37. Bansal T, Englert D, Lee J, Hegde M, Wood TK, Jayaraman A. Differential Effects of Epinephrine, Norepinephrine, and Indole on Escherichia coli O157:H7 Chemotaxis, Colonization, and Gene Expression. Infect Immun. 2007; 75(9):4597-607. DOI: 10.1128/IAI.00630-07
38. O’Donnell PM, Aviles H, Lyte M, Sonnenfeld G. Enhancement of In Vitro Growth of Pathogenic Bacteria by Norepinephrine: Importance of Inoculum Density and Role of Transferrin. Appl Environ Microbiol. 2006; 72(7):5097-9. DOI: 10.1128/AEM.00075-06
39. Masato A, Plotegher N, Boassa D, Bubacco L. Impaired dopamine metabolism in Parkinson’s disease pathogenesis. Mol Neurodegeneration. 2019; 14(1):35. DOI: 10.1186/s13024-019-0332-6
40. Luqman A, Nega M, Nguyen MT, Ebner P, Götz F. SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization. Cell Reports. 2018; 22(2):535-45. DOI: 10.1016/j.celrep.2017.12.058
41. Eisenhofer G, Åneman A, Friberg P, Hooper D, Fåndriks L, Lonroth H, et al. Substantial Production of Dopamine in the Human Gastrointestinal Tract. J Clin Endocrinol Metab. 1997 ; 82(11):3864-71. DOI: 10.1210/jcem.82.11.4339.
42. Sieghart W, Fuchs K, Tretter V, Ebert V, Jechlinger M, Höger H, et al. Structure and subunit composition of GABAA receptors. Neurochemistry International. 1999; 34(5):379-85. DOI: 10.1016/s0197-0186(99)00045-5
43. Korpi ER, Sinkkonen ST. GABA(A) receptor subtypes as targets for neuropsychiatric drug development. Pharmacology & Therapeutics. 2006; 109(1-2):12-32. DOI: 10.1016/j.pharmthera.2005.05.009
44. Duranti S, Ruiz L, Lugli GA, Tames H, Milani C, Mancabelli L, et al. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA. Sci Rep. 2020; 10(1):14112. DOI: 10.1038/s41598-020-70986-z
45. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA. 2011; 108(38):16050-5. DOI: 10.1073/pnas.1102999108
46. Kalueff AV, Nutt DJ. Role of GABA in anxiety and depression. Depress Anxiety. 2007; 24(7):495-517.
47. Chen Y, Xu J, Chen Y. Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients. 2021; 13(6):2099.
48. Sonali S, Ray B, Ahmed Tousif H, Rathipriya AG, Sunanda T, Mahalakshmi AM, et al. Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review. Cells. 2022; 11(8):1362. DOI: 10.3390/cells11081362
49. Haghighat N, Rajabi S, Mohammadshahi M. Effect of synbiotic and probiotic supplementation on serum brain-derived neurotrophic factor level, depression and anxiety symptoms in hemodialysis patients: a randomized, double-blinded, clinical trial. Nutr Neurosci. 2021; 24(6):490-499). DOI: 10.1080/1028415X.2019.1646975
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):299. DOI: 10.1186/s12888-020-02654-5
51. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The Human Microbiome Project. Nature. 2007; 449(7164):804-10. DOI: 10.1038/nature06244
52. Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med. 2016; 8(1):51. DOI: 10.1186/s13073-016-0307-y
Descargas
Publicado
Número
Sección
Licencia
Derechos de autor 2025 Ashly Verónica Arias-Obando, Nicoll Valentina Caamaño-Sierra, Ana Maria Pérez-Jiménez
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
La Revista Salutem Scientia Spiritus usa la licencia Creative Commons de Atribución – No comercial – Sin derivar: Los textos de la revista son posibles de ser descargados en versión PDF siempre que sea reconocida la autoría y el texto no tenga modificaciones de ningún tipo.
