The effects of probiotics on depressive symptoms in humans: a systematic review

Caroline J K Wallace, Roumen Milev, Caroline J K Wallace, Roumen Milev

Abstract

Background: Patients suffering from depression experience significant mood, anxiety, and cognitive symptoms. Currently, most antidepressants work by altering neurotransmitter activity in the brain to improve these symptoms. However, in the last decade, research has revealed an extensive bidirectional communication network between the gastrointestinal tract and the central nervous system, referred to as the "gut-brain axis." Advances in this field have linked psychiatric disorders to changes in the microbiome, making it a potential target for novel antidepressant treatments. The aim of this review is to analyze the current body of research assessing the effects of probiotics, on symptoms of depression in humans.

Methods: A systematic search of five databases was performed and study selection was completed using the preferred reporting items for systematic reviews and meta-analyses process.

Results: Ten studies met criteria and were analyzed for effects on mood, anxiety, and cognition. Five studies assessed mood symptoms, seven studies assessed anxiety symptoms, and three studies assessed cognition. The majority of the studies found positive results on all measures of depressive symptoms; however, the strain of probiotic, the dosing, and duration of treatment varied widely and no studies assessed sleep.

Conclusion: The evidence for probiotics alleviating depressive symptoms is compelling but additional double-blind randomized control trials in clinical populations are warranted to further assess efficacy.

Keywords: Anxiety; Depression; Gut–brain axis; Microbiome; Probiotics; Systematic review.

Figures

Fig. 1
Fig. 1
Flow chart of systematic literature search and selection process using preferred reporting items for systematic reviews and meta-analyses (PRISMA) process

References

    1. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617–627. doi: 10.1001/archpsyc.62.6.617.
    1. Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health. 2013;34:119. doi: 10.1146/annurev-publhealth-031912-114409.
    1. Anderson HD, Pace WD, Libby AM, et al. Rates of 5 common antidepressant side effects among new adult and adolescent cases of depression: a retrospective US claims study. Clin Ther. 2012;34(1):113–123. doi: 10.1016/j.clinthera.2011.11.024.
    1. Foster JA, Neufeld KAM. Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013;36(5):305–312. doi: 10.1016/j.tins.2013.01.005.
    1. Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186–194. doi: 10.1016/j.bbi.2015.03.016.
    1. Naseribafrouei A, Hestad K, Avershina E, et al. Correlation between the human fecal microbiota and depression. Neurogastroenterol Motil. 2014;26(8):1155–1162. doi: 10.1111/nmo.12378.
    1. Kelly JR, Borre Y, O’Brien C, et al. Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016;82:109–118. doi: 10.1016/j.jpsychires.2016.07.019.
    1. Walker EA, Katon WJ, Jemelka RP, et al. Comorbidity of gastrointestinal complaints, depression, and anxiety in the epidemiologic catchment area (ECA) study. Am J Med. 1992;92(1):S26–S30. doi: 10.1016/0002-9343(92)90133-V.
    1. Mangiola F, Ianiro G, Franceschi F, et al. Gut microbiota in autism and mood disorders. World J Gastroenterol. 2016;22(1):361. doi: 10.3748/wjg.v22.i1.361.
    1. Goodrich JK, Waters JL, Poole AC, et al. Human genetics shape the gut microbiome. Cell. 2014;159(4):789–799. doi: 10.1016/j.cell.2014.09.053.
    1. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222–227.
    1. Markle JG, Frank DN, Mortin-Toth S, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339(6123):1084–1088. doi: 10.1126/science.1233521.
    1. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–563. doi: 10.1038/nature12820.
    1. O’Mahony SM, Marchesi JR, Scully P, et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009;65(3):263–267. doi: 10.1016/j.biopsych.2008.06.026.
    1. Meddings JB, Swain MG. Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat. Gastroenterology. 2000;119(4):1019–1028. doi: 10.1053/gast.2000.18152.
    1. Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical implications of the brain–gut–enteric microbiota axis. Nat Rev Gastroenterol Hepatol. 2009;6(5):306–314. doi: 10.1038/nrgastro.2009.35.
    1. Logan AC, Jacka FN. Nutritional psychiatry research: and emerging discipline and its intersection with global urbanization, environmental challenges, and the evolutionary mismatch. J Physiol Anthropol. 2014;33(1):22. doi: 10.1186/1880-6805-33-22.
    1. Selhub EM, Logan AC, Bested AC. Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. J Physiol Anthropol. 2014;33(1):2. doi: 10.1186/1880-6805-33-2.
    1. Sanchez-Villegas A, Delgado-Rodriguez M, Alonso A, et al. Association of the Mediterranean dietary pattern with the incidence of depression: the Seguimiento Universidad de Navarra/University of Navarra follow-up (SUN) cohort. Arch Gen Psychiatry. 2009;66(10):1090–1098. doi: 10.1001/archgenpsychiatry.2009.129.
    1. Akbaraly TN, Brunner EJ, Ferrie JE, et al. Dietary pattern and depressive symptoms in middle age. Br J Psychiatry. 2009;195(5):408–413. doi: 10.1192/bjp.bp.108.058925.
    1. Dinan TG, Quigley EM. Probiotics in the treatment of depression: science or science fiction? Aust N Z J Psychiatry. 2011;45(12):1023–1025. doi: 10.3109/00048674.2011.613766.
    1. Parvez S, Malik KA, Ah Kang S, et al. Probiotics and their fermented food products are beneficial for health. J Appl Microbiol. 2006;100(6):1171–1185. doi: 10.1111/j.1365-2672.2006.02963.x.
    1. Logan AC, Katzman M. Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypotheses. 2005;64(3):533–538. doi: 10.1016/j.mehy.2004.08.019.
    1. Ait-Belgnaoui A, Durand H, Cartier C, et al. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology. 2012;37(11):1885–1895. doi: 10.1016/j.psyneuen.2012.03.024.
    1. Ait-Belgnaoui A, Colom A, Braniste V, et al. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil. 2014;26(4):510–520. doi: 10.1111/nmo.12295.
    1. 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. PNAS. 2011;108(38):16050–16055. doi: 10.1073/pnas.1102999108.
    1. Stetler C, Miller GE. Depression and hypothalamic–pituitary–adrenal activation: a quantitative summary of four decades of research. Psychosom Med. 2011;73(2):114–126. doi: 10.1097/PSY.0b013e31820ad12b.
    1. Sherwin E, Rea K, Dinan TG, et al. A gut (microbiome) feeling about the brain. Curr Opin Gastroenterol. 2016;32(2):96–102. doi: 10.1097/MOG.0000000000000244.
    1. Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008;64(6):527–532. doi: 10.1016/j.biopsych.2008.05.005.
    1. Desbonnet L, Garrett L, Clarke G, et al. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43(2):164–174. doi: 10.1016/j.jpsychires.2008.03.009.
    1. Nishino R, Mikami K, Takahashi H, et al. Commensal microbiota modulate murine behaviors in a strictly contamination-free environment confirmed by culture-based methods. Neurogastroenterol Motil. 2013;25(6):521–528. doi: 10.1111/nmo.12110.
    1. Luo J, Wang T, Liang S, et al. Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat. Sci China Life Sci. 2014;57(3):327–335. doi: 10.1007/s11427-014-4615-4.
    1. Savignac HM, Tramullas M, Kiely B, et al. Bifidobacteria modulate cognitive processes in an anxious mouse strain. Behav Brain Res. 2015;287:59–72. doi: 10.1016/j.bbr.2015.02.044.
    1. Smith CJ, Emge JR, Berzins K, et al. Probiotics normalize the gut–brain–microbiota axis in immunodeficient mice. Am J Physiol Gastrointest Liver Physiol. 2014;307(8):G793–G802. doi: 10.1152/ajpgi.00238.2014.
    1. Kantak PA, Bobrow DN, Nyby JG. Obsessive-compulsive-like behaviors in house mice are attenuated by a probiotic (Lactobacillus rhamnosus GG) Behav Pharmacol. 2014;25(1):71–79. doi: 10.1097/FBP.0000000000000013.
    1. Messaoudi M, Lalonde R, Violle N, 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;105(05):755–764. doi: 10.1017/S0007114510004319.
    1. Li S, Zhao Y, Zhang Y, et al. Antioxidant activity of Lactobacillus plantarum strains isolated from traditional Chinese fermented foods. Food Chem. 2012;135(3):1914–1919. doi: 10.1016/j.foodchem.2012.06.048.
    1. Dhakal R, Bajpai VK, Baek KH. Production of GABA by microorganisms: a review. Braz J Microbiol. 2012;43(4):1230–1241. doi: 10.1590/S1517-83822012000400001.
    1. Jumpertz R, Le DS, Turnbaugh PJ, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011;94:58–65. doi: 10.3945/ajcn.110.010132.
    1. Cepeda MS, Katz EG, Blacketer C. Microbiome–gut–brain axis: probiotics and their association with depression. J Neuropsychiatry Clin Neurosci 2016; appi-neuropsych.
    1. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12. doi: 10.1016/0197-2456(95)00134-4.
    1. Benton D, Williams C, Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2007;61(3):355–361. doi: 10.1038/sj.ejcn.1602546.
    1. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathogens. 2009;1(1):1. doi: 10.1186/1757-4749-1-6.
    1. Chung YC, Jin HM, Cui Y, et al. Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults. J Funct Foods. 2014;10:465–474. doi: 10.1016/j.jff.2014.07.007.
    1. Steenbergen L, Sellaro R, van Hemert S, et al. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015;48:258–264. doi: 10.1016/j.bbi.2015.04.003.
    1. Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi 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;32(3):315–320. doi: 10.1016/j.nut.2015.09.003.
    1. 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. doi: 10.4161/gmic.2.4.16108.
    1. Gruenwald J, Graubaum HJ, Harde A. Effect of a probiotic multivitamin compound on stress and exhaustion. Adv Ther. 2002;19(3):141–150. doi: 10.1007/BF02850270.
    1. Marcos A, Wärnberg J, Nova E, et al. The effect of milk fermented by yogurt cultures plus Lactobacillus casei DN-114001 on the immune response of subjects under academic examination stress. Eur J Nutr. 2004;43(6):381–389. doi: 10.1007/s00394-004-0517-8.
    1. Hilimire MR, DeVylder JE, Forestell CA. Fermented foods, neuroticism, and social anxiety: an interaction model. Psychiatry Res. 2015;228(2):203–208. doi: 10.1016/j.psychres.2015.04.023.
    1. Gartlehner G, Hansen RA, Carey TS, et al. Discontinuation rates for selective serotonin reuptake inhibitors and other second-generation antidepressants in outpatients with major depressive disorder: a systematic review and meta-analysis. Int Clin Psychopharmacol. 2005;20(2):59–69. doi: 10.1097/00004850-200503000-00001.
    1. Sirey JA, Bruce ML, Alexopoulos GS, et al. Stigma as a barrier to recovery: perceived stigma and patient-rated severity of illness as predictors of antidepressant drug adherence. Psychiatr Serv. 2001;52(12):1615–1620. doi: 10.1176/appi.ps.52.12.1615.
    1. Prescott SL, Logan AC. Transforming life: a broad view of the developmental origins of health and disease concept from an ecological justice perspective. Int J Environ Res Public Health. 2016;13(11):1075. doi: 10.3390/ijerph13111075.
    1. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013;74:720–726. doi: 10.1016/j.biopsych.2013.05.001.
    1. Maes M, Scharpé S, Meltzer HY, et al. Increased neopterin and interferon-gamma secretion and lower availability of l-tryptophan in major depression: further evidence for an immune response. Psychiatry Res. 1994;54(2):143–160. doi: 10.1016/0165-1781(94)90003-5.
    1. Owen BM, Eccleston D, Ferrier IN, et al. Raised levels of plasma interleukin-1β in major and postviral depression. Acta Psychiatr Scand. 2001;103(3):226–228. doi: 10.1034/j.1600-0447.2001.00162.x.
    1. Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009;71(2):171–186. doi: 10.1097/PSY.0b013e3181907c1b.
    1. Anisman H, Ravindran A, Griffiths J, et al. Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical. Mol Psychiatry. 1999;4:182–188. doi: 10.1038/sj.mp.4000436.
    1. Yirmiya R. Behavioral and psychological effects of immune activation: implications for ‘depression due to a general medical condition’. Curr Opin Psychiatry. 1997;10(6):470–476. doi: 10.1097/00001504-199711000-00011.
    1. Kawai T, Takeuchi O, Fujita T, et al. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol. 2001;167:5887–5894. doi: 10.4049/jimmunol.167.10.5887.
    1. Owens MJ, Nemeroff CB. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem. 1994;40(2):288–295.
    1. Mayer EA, Knight R, Mazmanian SK, et al. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014;34(46):15490–15496. doi: 10.1523/JNEUROSCI.3299-14.2014.
    1. Diop L, Guillou S, Durand H. Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: a double-blind, placebo-controlled, randomized trial. Nutr Res. 2008;28(1):1–5. doi: 10.1016/j.nutres.2007.10.001.
    1. Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastreoenterol. 2006;101(7):1581–1590. doi: 10.1111/j.1572-0241.2006.00734.x.
    1. Quitkin FM, Rabkin JG, Ross D, et al. Duration of antidepressant drug treatment: what is an adequate trial? Arch Gen Psychiatry. 1984;41(3):238–245. doi: 10.1001/archpsyc.1984.01790140028003.
    1. Paterson LM, Nutt DJ, Wilson SJ. NAPSAQ-1: National Patient Sleep Assessment Questionnaire in depression. Int J Psychiatry Clin Pract. 2009;13(1):48–58. doi: 10.1080/13651500802450498.
    1. Jackson ML, Butt H, Ball M, et al. Sleep quality and the treatment of intestinal microbiota imbalance in chronic fatigue syndrome: a pilot study. Sleep Science. 2015;8(3):124–133. doi: 10.1016/j.slsci.2015.10.001.
    1. Martin JK, Blum TC. Subclinical depression and performance at work. Soc Psychiatry Psychiatr Epidemiol. 1996;31(1):3–9.
    1. Judd LL, Paulus MP, Wells KB, et al. Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population. Am J Psychiatry. 1996;153(11):1411. doi: 10.1176/ajp.153.11.1411.
    1. Chachamovich E, Fleck M, Laidlaw K, et al. Impact of major depression and subsyndromal symptoms on quality of life and attitudes toward aging in an international sample of older adults. Gerontologist. 2008;48(5):593–602. doi: 10.1093/geront/48.5.593.
    1. Cukrowicz KC, Schlegel EF, Smith PN, et al. Suicide ideation among college students evidencing subclinical depression. J Am Coll Health. 2011;59(7):575–581. doi: 10.1080/07448481.2010.483710.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe