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

Agata Misera, Paweł Liśkiewicz, Igor Łoniewski, Karolina Skonieczna-Żydecka, Jerzy Samochowiec, Agata Misera, Paweł Liśkiewicz, Igor Łoniewski, Karolina Skonieczna-Żydecka, Jerzy Samochowiec

Abstract

Probiotics were shown to act positively on gut-brain axis signaling. We aimed to assess the effect of the administration of a new class of probiotics-psychobiotics-using data from individual psychometric scales, markers of the immune system and neuroactive metabolites. Medical databases were searched from database inception until 22 April 2021 for randomized clinical trials in clinically proven Major Depressive Disorder (MDD) patients treated with either probiotics or placebo reporting any psychometric score (PROSPERO registration number: CRD42021253024). Ten studies with 705 randomized participants and 603 analyzed were included. The mean age of individuals was 38.43 ± 12.1 years, predominantly women (n = 461, 76.45). The mean study duration was 48.8 ± 12.3 (range = 28-62) days. The dosage ranged between 1 × 109 to 2 × 1010 colony forming units (CFU)/day. We found that probiotics might alleviate symptoms of MDD; endpoint data (pooled scores): SMD = -0.292, 95%CI = -0.577 to -0.007, p < 0.044; change scores (BDI): SMD = -0.482, 95%CI = -0.854 to -0.109, p < 0.011; DM = -4.848, 95%CI = -8.559 to -1.137, p < 0.01. The therapy tended to be more effective with time of psychobiotic supplementation (coefficient = -0.12, SE = 0.06, Z = -1.84, p = 0.06) and in men (% of females: coefficient = 0.1, SE = 0.06, Z = 1.78, p = 0.07). Psychobiotics have great potential in the treatment of MDD. However, no specific strain/strains, dosage or duration of treatment can currently be recommended.

Keywords: depression; microbiota; probiotics; psychobiotics.

Conflict of interest statement

Igor Łoniewski is a probiotic company shareholder, Karolina Skonieczna-Żydecka receives remuneration from probiotic company.

Figures

Figure 1
Figure 1
Study flow chart. N/n = number of studies.
Figure 2
Figure 2
An effect size (random model), SDM, for depression symptoms in clinical scores in persons taking probiotics vs. placebos (controls). Q = 9.197, df(Q) = 5, p = 0.101, I2 = 45.632.
Figure 3
Figure 3
An effect size (random model), SDM, for depression symptoms in clinical scores in persons taking probiotics vs. placebos (controls) subgroup analysis BDI: Q = 1.924, df(Q) = 2, p = 0.382, I-squared = 0.0; HAMD: Q = 6.761, df(Q) = 2, p = 0.034, I2 = 70.41.
Figure 4
Figure 4
An effect size (random model), DM, for depression symptoms in clinical scores in persons taking probiotics vs. placebos (controls) subgroup analysis BDI: Q = 2.185, df(Q) = 2, p = 0.335, I-squared = 8.48; HAMD: Q = 5.399, df(Q) = 2, p = 0.067, I2 = 62.955.
Figure 5
Figure 5
Funnel plots for (A) SDM and (B) DM for the psychometric score at endpoint.
Figure 6
Figure 6
Regression for SDM on strains used in trials. References [26,30], Formula 1 [23,28], Formula 2 [21].
Figure 7
Figure 7
Regression for DM on (A) duration of supplementation abs (B)% of females participating in the trial.
Figure 8
Figure 8
(A). An effect size (random model), SDM, for depression symptoms in BDI change score in persons taking probiotics vs. placebos (controls). Overall: Q = 0.019, df(Q) = 1, p = 0.891, I-squared = 0.00; (B). An effect size (random model), DM for depression symptoms in BDI change scores in persons taking probiotics vs. placebos (controls). Overall: Q = 0.08, df(Q) = 1, p = 0.77, I2 = 0.00.

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