Suplementação com probióticos e depressão: estratégia terapêutica?
DOI:
https://doi.org/10.24220/2318-0897v28n1a4455Palavras-chave:
Depressão. Microbiota. Probióticos. Sintomas depressivos.Resumo
Evidências crescentes de que a microbiota intestinal pode influenciar no funcionamento do sistema nervoso central levaram à hipótese de que a suplementação com microrganismos chave pode ter um efeito positivo no tratamento da depressão. O objetivo desta revisão foi compilar dados da literatura científica sobre o impacto do uso de probióticos como estratégia terapêutica nos desfechos depressão e sintomas depressivos em humanos. As evidências compiladas nesta revisão indicam que a suplementação com probióticos apresenta potencial promissor como terapia adjuvante no tratamento dos sintomas associados ao transtorno de Depressão Maior e, principalmente, como ação preventiva de quadros depressivos em indivíduos saudáveis ou com depressão leve. O estado da arte aponta para o potencial efeito psicobiótico de determinadas culturas, tais como as espécies Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus helveticus, Bifidobacterium lactis, Bifidobacterium longum e Bifidobacterium bifidum recomendando-se para os próximos estudos a ênfase nas cepas específicas, dosagem e tempo de consumo para obtenção dos efeitos sobre o eixo intestino-cérebro.
Downloads
Referências
World Health Organization. Depression and other common mental disorders: Global health estimates. Geneva: WHO; 2017.
Motta CCL, Moré CLOO, Nunes CHSS. Atendimento psicológico ao paciente com diagnóstico de depressão na Atenção Básica. Ciênc Saúde Coletiva. 2017 [citado 2018 dez 18];22(3):911-20. Disponível em: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-81232017002300911&lng=pt&tlng=pt. Doi: http://dx.doi.org/10.1590/1413-81 232017223.27982015
Molina MRAL, Wiener CD, Branco JC, Jansen K, Souza LDM, Tomasi, E, et al. Prevalência de depressão em usuários de unidades de atenção primaria. Rev Psiq Clín. 2012 [citado 2018 Dez 18];39(6):194-7. Disponível em: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0101-60832012000600003&lng=pt. Doi: http://dx.doi.org/10.1590/S0101-60832012000600003
Sarris J, Logan AC, Akbaraly TN, Amminger GP, Balanzá-Martínez V, Freeman MP, et al. Nutritional medicine as mainstream in psychiatry. Lancet Psych. 2015 [cited 2018 Sep 10];2: 271-4. Available from: https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)00051-0/fulltext. Doi: http://dx.doi.org/10.1016/S2215-0366(14)00051-0
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR⁄D report. Am J Psych. 2006 [cited 2018 Sep 10];163:1905-17. Available from: https://ajp.psychiatryonline.org/doi/full/10.1176/ajp.2006.163.11.1905. Doi: http://dx.doi.org/10.1176/ajp.2006.163.11.1905
Parker G, Brotchie H. Depressão maior suscita questionamento maior. Rev Bras Psiquiatr. 2009 [citado 2018 dez 18];31Supl1:S3-6. Disponível em: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462009000500002 &lng=pt&tlng=pt. Doi: http://dx.doi.org/10.1590/S1516-44462009000500002
Ibanez G, Mercedes BPC, Vedana KGG, Miasso AI. Adesão e dificuldades relacionadas ao tratamento medicamentoso em pacientes com depressão. Rev Bras Enferm. 2014 [citado 2018 dez 18];67(4):556-62. Disponível em: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0034-71672014000400556&lng=pt. Doi: http://dx.doi.org/10.1590/00 34-7167.2014670409
Macqueen G, Surette M, Moayyedi P. The gut microbiota and psychiatric illness. J Psych Neurosci. 2017 [cited 2018 Sept 10];42(2): 75-7. Available from: http://jpn.ca/42-2-75. Doi: http://dx.doi.org/10.1503/jpn.170028
Naseribafrouei A, Hestad K, Avershina E, Sekelja M, Linløkken A, Wilson R, et al. Correlation between the human fecal microbiota and depression. Neurogastroenterol Motil. 2014 [cited 2018 Sep 12] ;26(8):1155-62. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/nmo.12378. Doi: http://dx.doi.org/10.1111/nmo.12378
Qin J, Li Y, Cai Z, Li S, Zhu J, Zhanget F, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012 [cited 2018 Sept 12];490(7418):55-60. Available from: https://www.nature.com/articles/nature11450. Doi: http://dx.doi.org/10.1038/nature11450
Saulnier D, Riehle K, Mistretta T, Diaz M, Mandal D, Raza S, et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology. 2011 [cited 2018 Sept 12];141(5):1782-91. Available from: https://www.gastrojournal.org/article/S0016-5085(11)00922-X/fulltext. Doi: http://dx.doi.org/10.1053/j.gastro.2011.06.072
Frémont M, Coomans D, Massart S, Meirleir K. High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients. Anaerobe. 2013 [cited 2018 Sept 12];22:50-6. Available from: https://www.sciencedirect.com/science/article/pii/S1075996413000929. Doi: http://dx.doi.org/10.1016/j.anaerobe.2013.06.002
Cryan JF, Dinan TG. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012 [cited 2018 Sept 12];13(10):701-12. Available from: https://www.nature.com/articles/nrn3346. Doi: http://dx.doi.org/10.1038/nrn3346
Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011 [cited 2018 Sept 12];141(2):599-609. Available from: https://www.gastrojournal.org/article/S0016-5085(11)00607-X/fulltext. Doi: http://dx.doi.org/10.1053/j.gastro.2011.04.052.
Bercik P, Collins SM, Verdu EF. Microbes and the gut-brain axis. Neurogastroenterol Motil. 2012 [cited 2018 Sept 14];24(5):405-13. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2982.2012.01906.x. Doi: http://dx.doi.org/10.1111/j.1365-2982.2012.01906.x
Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004 [cited 2018 Sept 13];558(1):263-75. Available from: https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/jphysiol.2004.063388. Doi: http://dx.doi.org/10.1113/jphysiol.2004.063388
Schmidt C. Mental health: Thinking from the gut. Sci Am. 2015 [cited 2018 Sept 13];312(3):S13-5. Available from: https://www.scientificamerican.com/article/mental-health-may-depend-on-creatures-in-the-gut/. Doi: http://dx.doi.org/10.1038/ scientificamerican0315-S12
Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Tóth M, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014 [cited 2018 Sept 13];6(263):1-12. Available from: https://stm.sciencemag.org/content/6/263/263ra158. Doi: http://dx.doi.org/10.1126/scitranslmed.3009759
Food and Agriculture Organization of the United Nations. Guidelines for the evaluation of probiotics in food. Geneva: WHO; 2002.
Heller KJ. Probiotic bacteria in fermented foods: Product characteristics and starter organisms. Am J Clin Nutr. 2001 [cited 2018 Sept 13];73(2):374-9. Available from: https://academic.oup.com/ajcn/article/73/2/374s/4737565. Doi: http://dx.doi.org/10.1093/ajcn/73.2.374s
Dinan TG, Stanton C, Cryan JF. Psychobiotics: A novel class of psychotropic. Biol Psych. 2013 [cited 2018 Sept 13];74(10):720-6. Available from: https://www.biologicalpsychiatryjournal.com/article/S0006-3223(13)00408-3/fulltext. Doi: http://dx.doi.org/10.1016/j.biopsych.2013.05.001
Logan AC, Katzman M. Major depressive disorder: Probiotics may be an adjuvant therapy. Med Hypotheses. 2005 [cited 2018 Sept 14];64(3):533-8. Available from: https://www.sciencedirect.com/science/article/abs/pii/ S0306987704004967. Doi: http://dx.doi.org/10.1016/j.mehy.2004.08.019
Dinan TG, Cryan JF. Mood by microbe: Towards clinical translation. Genome Med. 2016 [cited 2018 Sept 14];8:36. Available from: https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-016-0292-1. Doi: http://dx.doi.org/10.1186/s13073-016-0292-1
Kelly JR, Borre Y, O’ Brien C, Patterson E, El Aidy S, Deane J, et al. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016 [cited 2018 Sept 14];82:109-18. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0022395616301571. Doi: http://dx.doi.org/10.1016/j.jpsychires.2016.07.019
Kazemi A, Noorbala AA, Azam K, Eskandari MH, Djafarian K. Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial. Clin Nutr. 2019 [cited 2019 Jul 22];38(2):522-8. Available from: https://www.clinicalnutritionjournal.com/article/S0261-5614(18)30161-4/fulltext.Doi: http://dx.doi.org/10.1016/j.clnu.2018.04.010
Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, Jafari P, Akbari H, Taghizadeh M, et al. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition. 2016 [cited 2018 Sept 18];32(3):315-20. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0899900715003913. Doi: http://dx.doi.org/10.1016/j.nut.2015.09.003
Bambling M, Edwards SC, Hall S, Vitetta L. A combination of probiotics and magnesium orotate attenuate depression in a small SSRI resistant cohort: An intestinal anti-inflammatory response is suggested. Inflammopharmacol. 2017 [cited 2018 Sept 18];25(2): 271-4. Available from: https://link.springer.com/article/10.1007%2Fs10787-017-0311-x. Doi: http://dx.doi.org/10.1007/s10787-017-0311-x
Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011 [cited 2018 Sept 18];105(5):755-64. Available from: https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/assessment-of-psychotropiclike-properties-of-a-probiotic-formulation-lactobacillus-helveticus-r0052-and-bifidobacterium-longum-r0175-in-rats-and-human-subjects/2BD9977C6DB7EA40FC9FFA1933C024EA. Doi: http://dx.doi.org/10.1017/S0007114510004319
Mohammadi AA, Jazayeri S, Khosravi-darani K, Solati Z, Mohammadpour N, Asemi Z, et al. The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers. Nutr Neurosci. 2016 [cited 2018 Sept 16];19(9):387-95. Available from: https://www.tandfonline.com/doi/full/10.1179/1476830515Y.0000000023. Doi: http://dx.doi.org/10.1179/1476830515Y.0000000023
Inoue T, Kobayashi Y, Mori N, Sakagawa M, Xiao JZ, Moritani T, et al. Effect of combined bifidobacteria supplementation and resistance training on cognitive function, body composition and bowel habits of healthy elderly subjects. Benef Microbes. 2018 [cited 2018 Nov 14];9(6):843-53. Available from: https://www.wageningenacademic.com/doi/10.3920/BM2017.0193. Doi: http://dx.doi.org/10.3920/BM2017.0193
Steenbergen L, Sellaro R, Van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015 [cited 2018 Sept 18];48:258-64. Available from: https://www.sciencedirect.com/science/article/pii/S0889159115000884. Doi: http://dx.doi.org/10.1016/j.bbi.2015.04.003
Bagga D, Reichert JL, Koschutnig K, Aigner CS, Holzer P, Koskinen K, et al. Probiotics drive gut microbiome triggering emotional brain signatures. Gut Microbes. 2018 [cited 2018 Nov 14];9(6):486-96. Available from: https://www.tandfonline.com/doi/full/10.1080/19490976.2018.1460015. Doi: http://dx.doi.org/10.1080/19490976.2018.1460015
Östlund-lagerström L, Kihlgren A, Repsilber D, Björkstén B, Brummer RJ, Schoultz I. Probiotic administration among free-living older adults: A double blinded, randomized, placebo-controlled clinical trial. Nutr J. 2016 [cited 2018 Sept 18];15(1):1-10. Available from: https://nutritionj.biomedcentral.com/articles/10.1186/s12937-016-0198-1. Doi: http://dx.doi.org/10.1186/s12937-016-0198-1
Romijn AR, Rucklidge JJ, Kuijer RG, Frampton C. A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression. Aust N Z J Psychiatry. 2017 [cited 2018 Sept 18];51(8):810-21. Available from: https://journals.sagepub.com/doi/10.1177/0004867416686694. Doi: http://dx.doi.org/10.1177/0004867416686694
Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes. 2011 [cited 2018 Sept 18];2(4):256-61. Available from: https://www.tandfonline.com/doi/abs/10.4161/gmic.2.4.16108. Doi: http://dx.doi.org/10.4161/gmic.2.4.16108
Nolen-Hoeksema S, Wisco B, lyubomirsky S. Rethinking rumination. Perspect Psychol Sci. 2008 [cited 2018 Sept 24];3(5):400-24. Available from: https://journals.sagepub.com/doi/full/10.1111/j.1745-6924.2008.00088.x. Doi: http://dx.doi.org/10.1111/j.1745-6924.2008.00088.x
Mathews A, Macleod C. Cognitive vulnerability to emotional disorders. Annu Rev Clin Psychol. 2005 [cited 2018 Sept 24];1:167-95. Available from: https://www.annualreviews.org/doi/10.1146/annurev.clinpsy.1.102803.143916. Doi: http://dx.doi.org/10.1146/annurev.clinpsy.1.102803.143916
Scher CD, Ingram RE, Segal ZV. Cognitive reactivity and vulnerability: Empirical evaluation of construct activation and cognitive diatheses in unipolar depression. Clin Psychol Rev. 2005 [cited 2018 Sept 24];25(4):487-510. Available from: https://www.sciencedirect.com/science/article/pii/S0272735805000073. Doi: http://dx.doi.org/10.1016/j.cpr.2005.01.005
Martin JK, Blum TC, Beach SR, Roman PM. Subclinical depression and performance at work. Soc Psychiatry Psychiatr Epidemiol. 1996;31(1):3-9.
Judd L, Paulus P, Wells B, Rapaport H. Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population. Psychiatry. 1996 [cited 2018 Sept 24];153:1411-7. Available from: https://ajp.psychiatryonline.org/doi/abs/10.1176/ajp.153.11.1411. Doi: http://dx.doi.org/10.1176/ajp.153.11.1411
Chachamovich E, Fleck M, Laidlaw K, Power M. Impact of major depression and subsyndromal symptoms on quality of life and attitudes toward aging in an international sample of older adults. Gerontologist. 2008 [cited 2018 Sept 24];48(5):593-602. Available from: https://academic.oup.com/gerontologist/article/48/5/593/625284. Doi: http://dx.doi.org/10.1093/geront/48.5.593
Mainville I, Arcand Y, Farnworth ER. A dynamic model that simulates the human upper gastrointestinal tract for the study of probiotics. Inter J Food Microbiol. 2005 [cited 2018 Sept 24];99(3):287-96. Available from: https://www.sciencedirect.com/science/article/pii/S0168160504004416. Doi: http://dx.doi.org/10.1016/j.ijfoodmicro.2004.08.020
Barbosa FHF, Silva AM, Duarte R, Nicoli JR. Perfil de Susceptibilidade Antimicrobiana de Bifidobacterium bifidum Bb12 e Bifidobacterium longum Bb46. Rev Biol Ciênc Terra. 2001;1(2):1-12.
Kim N, Yun M, Oh YJ, Choi HJ. Mind-altering with the gut: Modulation of the gut-brain axis with probiotics. J Microbiol. 2018 [cited 2018 Sept 30];56(3):172-82. Available from: https://link.springer.com/article/10.1007%2Fs12275-018-8032-4. Doi: http://dx.doi.org/10.1007/s12275-018-8032-4
Bravo JA, Julio-Pieper M, Forsythe P, Kunze W, Dinan TG, Bienenstock J, et al. Communication between gastrointestinal bacteria and the nervous system. Curr Opin Pharmacol. 2012 [cited 2018 Sept 24];12(6):667-72. Available from: https://www.sciencedirect.com/science/article/pii/S1471489212001798. Doi: http://dx.doi.org/10.1016/j.coph.2012.09.010
Bercik P, Park AJ, Sinclair D, Khoshdel A, Lu J, Huang X, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil. 2011 [cited 2018 Sept 24];23(12):1132-39. Available from: https://www.gastrojournal.org/article/S0016-5085(11)00607-X/fulltext. Doi: http://dx.doi.org/10.1053/j.gastro.2011.04.052
Round JL, Mazmanian SK. The gut microbiome shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009 [cited 2018 Sept 24];9(5):313-23. Available from: https://www.nature.com/articles/nri2515. Doi: http://dx.doi.org/10.1038/nri2515
Perry VH, Anthony DC, Bolton SJ, Brown HC. The blood-brain barrier and the inflammatory response. Mol Med Today. 1997 [cited 2018 Sept 24];3(8):335-41. Available from: https://www.sciencedirect.com/science/article/pii/ S1357431097010770. Doi: http://dx.doi.org/10.1016/S1357-4310(97)01077-0
Miller A, Haroon E, Raison C, Felger J. Cytokine targets in the brain: Impact on neurotransmitters and neurocircuits. Depress Anxiety. 2013 [cited 2018 Sept 29];30(4):297-306. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/da.22084. Doi: http://dx.doi.org/10.1002/da.22084
Anisman H, Ravindran AV, Griffiths J. Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Mol Psychiatry. 1999;4(2):182-88.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psych. 2010 [cited 2018 Sept 10];67(5):446-57. Available from: https://www.biologicalpsychiatryjournal.com/article/S0006-3223(09)01229-3/fulltext. Doi: http://dx.doi.org/10.1016/j.biopsych.2009.09.033
Jones SE, Versalovic J. Probiotic Lactobacillus reuteri biofilms produce antimicrobial and anti-inflammatory factors. Biomed Central Microbiol. 2009 [cited 2018 Sept 29];9(35):1-9. Available from: https://bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-9-35. Doi: http://dx.doi.org/10.1186/1471-2180-9-35
Riedel CU, Foata F, Philippe D, Adolfsson O, Eikmanns BJ, Blum S. Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-κ B activation. World J Gastroenterol. 2006 [cited 2018 Sepy 29];12(23):3729-35. Available from: https://www.wjgnet.com/1007-9327/full/v12/i23/3729.htm. Doi: http://dx.doi.org/10.3748/wjg.v12.i23.3729
Wall R, Marques TM, O’Sullivan O, Ross RP, Shanahan F, Quigley EM, et al. Contrasting effects of Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 on the composition of murine brain fatty acids and gut microbiota. Am J Clin Nutr. 2012 [cited 2018 Sept 29];95:1278-87. Available from: https://academic.oup.com/ajcn/article/ 95/5/1278/4576936. Doi: http://dx.doi.org/10.3945/ajcn.111.026435
Jahangard L, Sadeghi A, Ahmadpanah M, Holsboer-Trachsler E, Sadeghi Bahmani D, Haghighi M, et al. Influence of adjuvant omega-3-polyunsaturated fatty acids on depression, sleep, and emotion regulation among outpatients with major depressive disorders: Results from a double-blind, randomized and placebo-controlled clinical trial. J Psychiatr Res. 2018 [cited 2018 Sept 29];1(107):48-56. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0022395618309890. Doi: http://dx.doi.org/10.1016/j.jpsychires.2018.09.016
Barrett E, Ross RP, O’toole PW, Fitzgerald GF, Stanton, C. γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol. 2012 [cited 2018 Sept 29];113(2):411-17. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2672.2012.05344.x. Doi: http://dx.doi.org/10.1111/j.1365-2672.2012.05344.x
Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015 [cited 2018 Sept 29];161(2):264-76. Available from: https://plu.mx/plum/a/?doi=10.1016/j.cell.2015.02.047. Doi: http://dx.doi.org/10.1016/j.cell.2015.02.047
Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: Mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 2013 [cited 2018 Sept 10];6(1):39-51. Available from: https://journals.sagepub.com/doi/10.1177/1756283X12459294. Doi: http://dx.doi.org/10.1177/1756283X12459294
Martin FJ, Sprenger N, Yap IKS, Wang Y, Bibiloni R, Rochat F, et al. Panorganismal gut microbiome: Host metabolic crosstalk research articles. J Proteome Res. 2009 [cited 2019 Nov 18];8:2090-105. Available from: https://pubs.acs.org/doi/abs/10.1021/pr801068x. Doi: http://dx.doi.org/10.1021/pr801068x
Segain J, Blétière DR, Bourreille A, Leray V, Gervois N, Rosales C, et al. Butyrate inhibits inflammatory responses through NF B inhibition: Implications for Crohn’s disease. Gut. 2000 [cited 2019 Nov 18];47:397-403. Available from: https://gut.bmj.com/content/47/3/397. Doi: http://dx.doi.org/10.1136/gut.47.3.397
Stilling RM, Dinan TG, Cryan, JF. Microbial genes, brain and behaviour–epigenetic regulation of the gut–brain axis. Genes Brain Behav. 2014 [cited 2019 Nov 21];13:69-86. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/gbb.12109. Doi: http://dx.doi.org/10.1111/gbb.12109
Schwarcz R, Bruno JP, Muchowski P, Wu H. Kynurenines in the mammalian brain: When physiology meets pathology. Nat Rev Neurosci. 2012 [cited 2019 Nov 21];13(1):465-77. Available from: https://www.nature.com/articles/nrn3257. Doi: http://dx.doi.org/10.1038/nrn3257
Marin IA, Goertz JE, Ren T, Rich SS, Onengut-Gumuscu S, Farber E, et al. Microbiota alteration is associated with the development of stress-induced despair behavior. Sci Rep. 2017 [cited 2019 Nov 21];7:1-10. Available from: https://www.nature.com/articles/srep43859. Doi: http://dx.doi.org/10.1038/srep43859
Vismari L, Alves GJ, Palermo-Neto J. Depression, antidepressants and immune system: A new look to an old problem. Rev Psiquiatr Clin. 2008 [cited 2019 Nov 21];35(5):196-204. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0101-60832008000500004 &lng=pt&nrm=iso&tlng=en. Doi: http://dx.doi.org/10.1590/S0101-60832008000500004
Kleiman SC, Bulik-Sullivan EC, Glenny EM, Zerwas SC, Huh EY, Tsilimigras MCB. The gut-brain axis in healthy females: Lack of significant association between microbial composition and diversity with psychiatric measures. PLoS One. 2017 [cited 2019 Nov 21];12(1):1-14. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170208. Doi: http://dx.doi.org/10.1371/journal.pone.0170208
Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015 [cited 2019 Nov 21];48:186-94. Available from: https://www.sciencedirect.com/science/article/pii/S0889159115001105. Doi: http://dx.doi.org/10.1016/j.bbi.2015.03.016
Sghir A, Gramet G, Suau A, Rochet V, Pochart P, Dore J. Quantification of bacterial groups within human fecal flora by oligonucleotide probe hybridization. Appl Environ Microbiol. 2000 [cited 2019 Nov 22];66(5):2263-66. Available from: https://aem.asm.org/content/66/5/2263. Doi: http://dx.doi.org/10.1128/AEM.66.5.2263-2266.2000
Cowen PJ. Serotonin and depression: Pathophysiological mechanism or marketing myth? Trends Pharmacol Sci. 2008 [cited 2019 Nov 22];29(9):433-36. Available from: https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(08)00126-0. Doi: http://dx.doi.org/10.1016/j.tips.2008.05.004
