Effects of a Psychobiotic Supplement on Serum Brain-derived Neurotrophic Factor Levels in Depressive Patients: A Post Hoc Analysis of a Randomized Clinical Trial

Abstract

Background/Aims Psychobiotics are probiotics or prebiotics that, upon ingestion in adequate amounts, yield positive influence on mental health via microbiota-gut-brain axis regulation to modulate the circulating cytokines, chemokines, neurotransmitters, or neurotrophins levels. We have recently shown that a psychobiotic combination (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175; CEREBIOME) significantly improved depression symptoms in patients with depression. Recent animal data suggest the influence of the gut microbiota on brain-derived neurotrophic factor (BDNF), which was shown to correlate with antidepressant response in depressive patients. Therefore, we conducted this exploratory post hoc analysis of BDNF levels to clarify the mechanism of action of this psychobiotic in our cohort. Methods Our study was a double-blind, randomized controlled trial of patients with low-to-moderate depression receiving either a probiotic combination, prebiotic or placebo. From the 110 patients randomized in the trial, 78 were included in this post hoc analysis (probiotic, n = 28; prebiotic and placebo, n = 25). We compared serum BDNF levels from participants at baseline and endpoint, and assessed the Pearson correlation between depression severity and BDNF levels for each intervention. Results We found that post-intervention BDNF levels were significantly different between groups (P < 0.001). Furthermore, BDNF levels increased significantly in the probiotic group compared to both the prebiotic (P < 0.001) and placebo groups (P = 0.021), which inversely correlated with depression severity compared to placebo (ANOVA/ANCOVA, P = 0.012; Pearson, r =-0.79, P < 0.001). In the prebiotic group, BDNF levels reduced but not significantly compared with placebo group (P > 0.05). Conclusion Eight-week supplementation with B. longum and L. helveticus in depressive patients improved depression symptoms, possibly by increasing BDNF levels.

Updated Review and Meta-Analysis of Probiotics for the Treatment of Clinical Depression: Adjunctive vs. Stand-Alone Treatment

“…C-reactive protein (CRP) was significantly reduced in the probiotic arm (compared to placebo) in a study that applied probiotics as adjunctive therapy [ 28 ], but not in a study of medication-free participants [ 33 ]. Similarly, BDNF was found to be significantly increased following probiotic treatment only when this was applied as adjunctive [ 36 ], and not as stand-alone treatment [ 33 ]. Interestingly, an inverse correlation between increases in BDNF and depression severity were also reported in this study [ 36 ].…”

“…Similarly, BDNF was found to be significantly increased following probiotic treatment only when this was applied as adjunctive [ 36 ], and not as stand-alone treatment [ 33 ]. Interestingly, an inverse correlation between increases in BDNF and depression severity were also reported in this study [ 36 ]. The tryptophane/kynurenine ratio was measured in two add-on studies, but only found to significantly differ in one, with a reduction in the probiotic arm [ 29 ].…”

“…Attenuations in serum levels of the growth factor BDNF have been linked to depression, and importantly, to antidepressant response [ 5 ]. Indeed, the study that found a significant increase of BDNF in the probiotic group compared to the placebo group also reported a significant correlation between increases in BDNF and BDI score reduction [ 36 ]. Both RCTs that measured BDNF used the same probiotic strains ( L. helveticus + B. longum ), which have previously been linked to BDNF increases in a mouse model of depression [ 14 ].…”

“…Kazemi (2019) [36] Significantly increased in the probiotic group compared to placebo post-treatment. This was significantly correlated with reduction in depressive scores.…”

Effect of Psychobiotics on Psychometric Tests and Inflammatory Markers in Major Depressive Disorder: Meta-Analysis of Randomized Controlled Trials with Meta-Regression

“…Studies were predominantly conducted in Iran (N = 5) [21][22][23][24][25] but also in Austria (N = 2) [26,27], Poland (N = 1) [28] and Italy (N = 1) [29]. One study was conducted in two clinical centers, in Australia and Netherlands (N = 1) [30].…”