Effects of Probiotic and Prebiotic Supplements on Serum BDNF, Kynurenine, Tryptophan Competing Amino Acids and Intestinal Microbiome in Major Depressed Patients

Abstract

Recent studies highlighted the role of disturbed intestinal microbiome in development of depression. Probiotics and prebiotics can be useful in prevention and treatment of depression as they can balance the intestinal microbiome and modulate the gut-brain axis. The aim of this double-blind randomized controlled clinical study was to compare the effects of Lactobacillus helveticus and Bifidobacterium longum probiotics and galacto-oligosaccharide prebiotic on serum brain derived neurotrophic factor (BDNF), kynurenine, tryptophan competing branched chain amino acids (BCAA) and intestinal microbiome in patients with major depressive disorder. A total of 110 patients (78 female and 32 male, aged 20-50 years) with low to moderate depression, who referred to psychiatric clinic of Bahman Hospital in Iran, were included and randomly assigned to one of the probiotic (n=38), prebiotic (n=36) and placebo (n=36) groups and 81 patients completed the study. Dietary intake using dietary recall, and physical activity level using international physical activity questionnaire were recorded at the baseline and endpoint. Furthermore, Height and weight of the participants were measured and body mass indexes (BMI) were calculated. Depression severity assessed using Beck’s depression inventory (BDI). Serum BDNF, kynurenine, BCAA, and intestinal microbiome levels were measured before and after the intervention. Serum BDNF and kynurenine levels were measured using ELISA. Amino acids were measured by HPLC. Intestinal microbiome was measured using real-time PCR. Totally, 81 patients (28 in the probiotic, 27 in the prebiotic and 26 in the placebo groups) with a mean age of 36.5 years and mean depression duration of 2.3 years completed the study. There was no significant difference among the three groups in terms of mean age, BMI and activity before and after intervention. Dietary intake was not different between groups at the endpoint except for selenium which was lower in probiotic group compared to placebo (P= 0.05). Probiotic use significantly reduced Beck depression scores (P= 0.042) and kynurenine to tryptophan ratio (P= 0.048) while increased tryptophan to isoleucine ratio (P= 0.023) compared to placebo, whereas prebiotic had no effect on these outcomes. Furthermore the rise in BDNF levels was significant in probiotic group compared to both prebiotic (P<0.001) and placebo (P=0.02) groups. Additionally, the increase in intestinal Lactobacillus group and Bifidobacterium spp. in probiotic group was significant compared to prebiotic group (P= 0.014 and P=0.025, respectively). This study showed that probiotic supplementation improves depression status probably by increasing intestinal Lactobacillus group and Bifidobacterium spp. and serum BDNF and reducing kynurenine to tryptophan ratio, whereas prebiotics had no effect on depression status.