Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial

Nutrition. 2016 Mar;32(3):315-20. doi: 10.1016/j.nut.2015.09.003. Epub 2015 Sep 28.


Objective: We are aware of no study examining the effects of probiotic supplementation on symptoms of depression, metabolic profiles, serum high-sensitivity C-reactive protein (hs-CRP), and biomarkers of oxidative stress in patients with major depressive disorder (MDD). The present study was designed to determine the effects of probiotic intake on symptoms of depression and metabolic status in patients with MDD.

Methods: This randomized, double-blind, placebo-controlled clinical trial included 40 patients with a diagnosis of MDD based on DSM-IV criteria whose age ranged between 20 and 55 y. Patients were randomly allocated into two groups to receive either probiotic supplements (n = 20) or placebo (n = 20) for 8 wk. Probiotic capsule consisted of three viable and freeze-dried strains: Lactobacillus acidophilus (2 × 10(9) CFU/g), Lactobacillus casei (2 × 10(9) CFU/g), and Bifidobacterium bifidum (2 × 10(9) CFU/g). Fasting blood samples were taken at the beginning and end of the trial to quantify the relevant variables. All participants provided three dietary records (two weekdays and one weekend) and three physical activity records during the intervention.

Results: Dietary intake of study participants was not significantly different between the two groups. After 8 wk of intervention, patients who received probiotic supplements had significantly decreased Beck Depression Inventory total scores (-5.7 ± 6.4 vs. -1.5 ± 4.8, P = 0.001) compared with the placebo. In addition, significant decreases in serum insulin levels (-2.3 ± 4.1 vs. 2.6 ± 9.3 μIU/mL, P = 0.03), homeostasis model assessment of insulin resistance (-0.6 ± 1.2 vs. 0.6 ± 2.1, P = 0.03), and serum hs-CRP concentrations (-1138.7 ± 2274.9 vs. 188.4 ± 1455.5 ng/mL, P = 0.03) were observed after the probiotic supplementation compared with the placebo. Additionally, taking probiotics resulted in a significant rise in plasma total glutathione levels (1.8 ± 83.1 vs. -106.8 ± 190.7 μmol/L, P = 0.02) compared with the placebo. We did not find any significant change in fasting plasma glucose, homeostatic model assessment of beta cell function, quantitative insulin sensitivity check index, lipid profiles, and total antioxidant capacity levels.

Conclusions: Probiotic administration in patients with MDD for 8 wk had beneficial effects on Beck Depression Inventory, insulin, homeostasis model assessment of insulin resistance, hs-CRP concentrations, and glutathione concentrations, but did not influence fasting plasma glucose, homeostatic model assessment of beta cell function, quantitative insulin sensitivity check index, lipid profiles, and total antioxidant capacity levels.

Keywords: Depression; Glucose metabolism; Lipid profiles; Oxidative stress; Probiotics.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bifidobacterium
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • C-Reactive Protein / metabolism
  • Cholesterol / blood
  • Depressive Disorder, Major / therapy*
  • Diet Records
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Glutathione / blood
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Lactobacillus acidophilus
  • Lactobacillus casei
  • Male
  • Middle Aged
  • Motor Activity
  • Oxidative Stress
  • Probiotics / administration & dosage*
  • Surveys and Questionnaires
  • Treatment Outcome
  • Triglycerides / blood
  • Young Adult


  • Biomarkers
  • Blood Glucose
  • Insulin
  • Triglycerides
  • C-Reactive Protein
  • Cholesterol
  • Glutathione

Associated data

  • IRCT/IRCT2014060717993N1