The aim of this study is to determine the effect of probiotic capsule supplementation on depression severity, plasma BDNF (brain drived neurotrophic factor), Cortisol & ACTH (adernocorticotropic hormon) in major depressive disorder patient under treatment with fluoxetine. Study design: Randomized double-blinded controlled clinical trial. Inclusion Criteria: Patients with major depressive according to DSM-IV-TR criteria that they have not use any supplement and antidepressant drug at least 2 months prior to the start of the project, aged 18 to 65 years, at least score 15 on Hamilton Depression Rating Scale 17 (HDRS-17). Exclusion Criteria: Pregnancy and lactation, drug abuse within 6 months prior to the start of the project, psychosis, any type of severe chronic physical illness and any extreme and severe mental disorders (suicidal ideation, psychotic symptoms, symptoms of manic phase, etc) will be excluded. Population and sample size: 40 patients with major depressive disorder of eligible and referred to Roozbeh hospital to Tehran University of Medical Sciences, Tehran, Iran in the study will be selected. Intervention: Patients will be assigned to receive either the probiotic capsule (intervention group: n=20) or placebo capsule (control group: n=20). Blood samples will be taken at baseline and after 8-wk intervention. Intervention: 8 weeks. Outcomes: Depression sivierity will be measured at the beginning, end of forth week and end of the intervention; plasma BDNF and ACTH, and serum cortisol will be measured at the beginning and end of the intervention too.