Probióticos como terapia adjuvante na depressão: revisão narrativa das evidências recentes (2020–2025)
DOI:
https://doi.org/10.25118/2763-9037.2026.v16.1551Palavras-chave:
depressão, probióticos, microbiota intestinal, psicobióticos, inflamaçãoResumo
Introdução: A depressão é uma das principais causas de incapacidade no mundo e grande parte dos pacientes mantém sintomas residuais ou resposta parcial ao tratamento convencional. A modulação da microbiota intestinal tem sido investigada como estratégia adjuvante promissora no manejo da depressão. Objetivo: Sintetizar criticamente as evidências recentes sobre o uso de probióticos como terapia adjuvante em indivíduos com sintomas depressivos. Métodos: Revisão narrativa de artigos indexados na base PubMed/MEDLINE, publicados entre janeiro de 2020 e março de 2025, nos idiomas inglês, português ou espanhol. Foram incluídos ensaios clínicos randomizados, estudos piloto, observacionais e ensaios controlados que avaliaram probióticos em indivíduos com sintomas depressivos, utilizando escalas padronizadas de depressão. Estudos sem desfechos depressivos, sem descrição de cepas, dose ou duração, bem como revisões, editoriais e relatos de caso foram excluídos. Resultados: Dezoito estudos foram inicialmente identificados, dos quais 11 preencheram os critérios de inclusão. A maioria dos ensaios demonstrou redução estatisticamente significativa de sintomas depressivos quando probióticos foram utilizados como adjuvantes, especialmente em quadros leves a moderados ou em pacientes com resposta parcial a antidepressivos. Foram também observadas melhoras em parâmetros de sono, fadiga, cognição e modulação de marcadores inflamatórios e neurotróficos, notadamente IL-6, TNF-α e BDNF. As intervenções foram, em geral, bem toleradas, embora haja subnotificação de eventos adversos. Conclusão: Probióticos despontam como estratégias adjuvantes promissoras no tratamento da depressão, com potenciais benefícios sobre sintomas residuais, sono, cognição e inflamação. No entanto, a heterogeneidade de cepas, doses e desfechos, aliada à escassez de estudos de longo prazo, impede recomendações padronizadas. Seu uso clínico deve ser criterioso, individualizado e sempre integrado a abordagens farmacológicas e psicoterapêuticas baseadas em evidências.
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1. World Health Organization. World mental health report: transforming mental health for all. Geneva: World Health Organization; 2022.
2. Chowdhury R, Trujillo N, Khalid S. Biosocial determinants and solutions for mental health conditions in low- and middle-income countries: revealing the current evidence gaps. Front Public Health. 2025;13:1691121. https://doi.org/10.3389/fpubh.2025.1691121 PMid:41018775 PMCid:PMC12465909
3. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-17. https://doi.org/10.1176/ajp.2006.163.11.1905 PMid:17074942
4. Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JPT, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JPA, Geddes JR. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357-66. https://doi.org/10.1016/S0140-6736(17)32802-7 PMid:29477251 PMCid:PMC5889788
5. Jones BDM, Daskalakis ZJ, Carvalho AF, Vieta E, Mulsant BH. Inflammation as a treatment target in mood disorders. BJPsych Open. 2020;6(4):e60. https://doi.org/10.1192/bjo.2020.43 PMid:32498754 PMCid:PMC7345526
6. Morais LH, Schreiber HL IV, Mazmanian SK. The gut microbiota-brain axis in behaviour and brain disorders. Nat Rev Microbiol. 2021;19(4):241-55. https://doi.org/10.1038/s41579-020-00460-0 PMid:33093662
7. Nikolova VL, Hall MRB, Hall LJ, Cleare AJ, Stone JM, Young AH. Acceptability, tolerability, and estimates of putative treatment effects of probiotics as adjunctive treatment in patients with depression: a randomized clinical trial. JAMA Psychiatry. 2023;80(8):842-7. https://doi.org/10.1001/jamapsychiatry.2023.1817 PMid:37314797 PMCid:PMC10267847
8. Reiter A, Bengesser SA, Hauschild AC, Birner A, Fellendorf FT, Platzer M, Färber T, Seidl M, Mendel LM, Unterweger R, Lenger M, Mörkl S, Dalkner N, Birner A, Queissner R, Hamm C, Maget A, Pilz R, Kohlhammer-Dohr A, Wagner-Skacel J, Kreuzer K, Schöggl H, Amberger-Otti D, Lahousen T, Leitner-Afschar B, Haybäck J, Kapfhammer H-P, Reininghaus E. Interleukin-6 gene expression changes after a 4-week intake of a multispecies probiotic in major depressive disorder-preliminary results of the PROVIT study. Nutrients. 2020;12(9):2575. https://doi.org/10.3390/nu12092575 PMid:32858844 PMCid:PMC7551871
9. Kim CS, Cha L, Sim M, Jung S, Chun WY, Baik HW, Shin D-M. Probiotic supplementation improves cognitive function and mood with changes in gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial. J Gerontol A Biol Sci Med Sci. 2021;76(1):32-40. https://doi.org/10.1093/gerona/glaa090 PMid:32300799 PMCid:PMC7861012
10. Schneider E, Doll JPK, Schweinfurth N, Kettelhack C, Schaub A-C, Yamanbaeva G, Varghese N, Mählmann L, Brand S, Eckert A, Borgwardt S, Lang UE, Schmidt A. Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial. J Psychiatry Neurosci. 2023;48(1):E23-33. https://doi.org/10.1503/jpn.220117 PMid:36653035 PMCid:PMC9854921
11. Ho YT, Tsai Y-C, Kuo TBJ, Yang CCH. Effects of Lactobacillus plantarum PS128 on depressive symptoms and sleep quality in self-reported insomniacs: a randomized, double-blind, placebo-controlled pilot trial. Nutrients. 2021;13(8):2820. https://doi.org/10.3390/nu13082820 PMid:34444980 PMCid:PMC8402034
12. Chen HM, Kuo P-H, Hsu C-Y, Chiu Y-H, Liu Y-W, Lu M-L, Chen C-H. Psychophysiological effects of Lactobacillus plantarum PS128 in patients with major depressive disorder: a preliminary 8-week open trial. Nutrients. 2021;13(11):3731. https://doi.org/10.3390/nu13113731 PMid:34835987 PMCid:PMC8618644
13. Saccarello A, Montarsolo P, Massardo I, Picciotto R, Pedemonte A, Castagnaro R, Brasesco PC, Guida V, Picco P, Fioravanti P, Montisci R, Schiavetti I, Vanelli A. Oral administration of S-adenosylmethionine (SAMe) and Lactobacillus plantarum HEAL9 improves the mild-to-moderate symptoms of depression: a randomized, double-blind, placebo-controlled study. Prim Care Companion CNS Disord. 2020;22(4):23164. https://doi.org/10.4088/PCC.19m02578 PMid:32589828
14. Ullah H, Khan A, Rengasamy KRR, Di Minno A, Sacchi R, Daglia M. The efficacy of S-adenosyl methionine and probiotic supplementation on depression: a synergistic approach. Nutrients. 2022;14(13):2751. https://doi.org/10.3390/nu14132751 PMid:35807931 PMCid:PMC9268496
15. Strodl E, Bambling M, Parnam S, Ritchie G, Cramb S, Vitetta L. Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trial. Sci Rep. 2024;14(1):20841. https://doi.org/10.1038/s41598-024-71093-z PMid:39242786 PMCid:PMC11379959
16. Reininghaus EZ, Platzer M, Kohlhammer-Dohr A, Hamm C, Mörkl S, Bengesser SA, Fellendorf FT, Lahousen-Luxenberger T, Leitner-Afschar B, Schöggl H, Amberger-Otti D, Wurm W, Queissner R, Birner A, Falzberger VS, Painold A, Fitz W, Wagner-Skacel J, Brunnmayr M, Rieger A, Maget A, Unterweger R, Schwalsberger K, Reininghaus B, Lenger M, Bastiaanssen TFS, Dalkner N. PROVIT: supplementary probiotic treatment and vitamin B7 in depression-a randomized controlled trial. Nutrients. 2020;12(11):3422. https://doi.org/10.3390/nu12113422 PMid:33171595 PMCid:PMC7695208
17. Schaub AC, Schneider E, Vazquez-Castellanos JF, Schweinfurth N, Kettelhack C, Doll JPK, Yamanbaeva G, Mählmann L, Brand S, Beglinger C, Borgwardt S Raes, J, Schmidt A, Lang UE. Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial. Transl Psychiatry. 2022;12(1):227. https://doi.org/10.1038/s41398-022-01977-z PMid:35654766 PMCid:PMC9163095
18. Hulkkonen P, Kataja E-L, Vahlberg T, Koivuniemi E, Houttu N, Pellonperä O, Mokkala K, Karlsson H, Laitinen K. The efficacy of probiotics and/or n-3 long-chain polyunsaturated fatty acids intervention on maternal prenatal and postnatal depressive and anxiety symptoms among overweight and obese women. J Affect Disord. 2021;289:21-30. https://doi.org/10.1016/j.jad.2021.04.006 PMid:33930612
19. Inserra A, Rogers GB, Licinio J, Wong ML. The microbiota-inflammasome hypothesis of major depression. Bioessays. 2018;40(9):1800027. https://doi.org/10.1002/bies.201800027 PMid:30004130 PMCid:PMC12180310
20. Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol. 2020;11:508738. https://doi.org/10.3389/fendo.2020.00025 PMid:32082260 PMCid:PMC7005631
21. Slykerman RF, Davies N, Vlckova K, O'Riordan KJ, Bassett SA, Dekker J, Schellekens H, Hyland NP Clarke, G, Patterson E. Precision psychobiotics for gut-brain axis health: advancing the discovery pipelines to deliver mechanistic pathways and proven health efficacy. Microb Biotechnol. 2025;18(1):e70079. https://doi.org/10.1111/1751-7915.70079 PMid:39815671 PMCid:PMC11735468
22. Chen X, Xu D, Yu J, Song X-J, Li X, Cui Y-L. Tryptophan metabolism disorder-triggered diseases, mechanisms, and therapeutic strategies: a scientometric review. Nutrients. 2024;16(19):3380. https://doi.org/10.3390/nu16193380 PMid:39408347 PMCid:PMC11478743
23. Cruz-Pereira JS, Rea K, Nolan YM, O'Leary OF, Dinan TG, Cryan JF. Depression's unholy trinity: dysregulated stress, immunity, and the microbiome. Annu Rev Psychol. 2020;71(1):49-78. https://doi.org/10.1146/annurev-psych-122216-011613 PMid:31567042
24. Nava RG, Adri AS, Filgueiras IS, Nóbile AL, Barcelos PM, Corrêa YLG, de Oliveira SF, Cabral-Miranda G, Dias HD, Schimke LF, Gleizer RAr, Dalmolin RJS, Nakaya HI, Rezende RM, Cabral-Marques O. Modulation of neuroimmune cytokine networks by antidepressants: implications in mood regulation. Transl Psychiatry. 2025;15(1):314. https://doi.org/10.1038/s41398-025-03532-y PMid:40849324 PMCid:PMC12375052
25. Horn J, Mayer DE, Chen S, Mayer EA. Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders. Transl Psychiatry. 2022;12(1):164. https://doi.org/10.1038/s41398-022-01922-0 PMid:35443740 PMCid:PMC9021202
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Copyright (c) 2026 Gustavo Nascimento Monteiro Siqueira, Breno José de Souza, Carlos Alberto José de Souza, Ranya Mirelle Santos de Medeiros, Brenda de Santana Silva, Danilo Bastos Bispo Ferreira
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