PRO-DEMET Randomized Controlled Trial on Probiotics in Depression—Pilot Study Results

Abstract

There is a pressing need to identify new treatment options for depression and its comorbidities. Depression often coexists with metabolic complications, and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Microbiota interventions (e.g., probiotics) may represent a safe and easy-to-use treatment option as an adjunctive therapy in patients only partially responsive to pharmacologic treatment. (1) Objective: The paper presents the results of a feasibility and pilot study. The study is an internal part of a randomized controlled trail (RCT) of the effect of probiotic supplementation on psychometric, anthropometric, metabolic, and inflammatory parameters in adult patients with depressive disorders depending on the presence of metabolic syndrome. (2) Methods: The trial has a four-arm, parallel-group, prospective, randomized, double-blind, controlled design. Sixty participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. The feasibility of the study design was assessed, as well as the rates of recruitment, eligibility, consent, and study completion. The following were assessed: depressive, anxiety and stress symptoms, quality of life, blood pressure, body mass index and waist circumference, complete blood count with differential, serum levels of C-reactive protein, high-density lipoprotein cholesterol, triglycerides, fasting glucose, some secondary markers of inflammation and metabolic health, as well as noninvasive biomarkers of liver fibrosis (APRI and FIB-4). (3) Results: The study was found to be generally feasible. The eligibility rate was 52% of recruited participants with 80% completing the study protocol. No differences in sociodemographic or anthropometric factors or basic laboratory findings were found between the placebo and probiotic group at the start of the intervention period. Importantly, the proportion of recruited participants fulfilling the criteria of metabolic syndrome was too low. (4) Conclusions: Whilst the whole study protocol was feasible, some different timepoint procedures require modification. The major weakness of the recruitment methods was that the percentage of metabolic arms participants was insufficient. Overall, the full RCT design on probiotics in depression with vs. without metabolic syndrome was shown to be feasible with little modification.

Probiotics’ Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014–2023 Clinical Trials

“…Most of the studies included in this review support the beneficial effects of probiotics. Kazemi et al [ 46 ] demonstrated a significant decrease in BDI score (17.39–9.1) compared to placebo (18.18–15.55) ( p = 0.042), after an 8-week use of a probiotic supplement as the main treatment, while Gawlik-Kotelnicka et al also demonstrated clinically significant improvement in MADRS and QoL (quality of life) scores [ 63 ]. On the same basis, Schaub et al [ 45 ] showed significant improvement in depression at the 8-week follow up, with a remission rate of 55% in the probiotics group compared to a 40% in the placebo group, but only for the one subgroup with high compliance of a short-term, high-dose intake of probiotics as a supplementary treatment for depression.…”

“…Chen et al [ 54 ] also reported correlations between fluctuations in IL-6 levels and the abundance of the genus Akkermansia . Additionally, Gawlik-Kotelnicka et al [ 63 ] reported reduced inflammation marker levels due to probiotics usage, while Miyaoka et al [ 60 ] also suggested that C. butyricum M588 may have significant anti-inflammatory effects. Furthermore, recent data from Yang et al [ 51 ] showed that serum corticotrophin-releasing hormone (CRF) levels and heart rate of healthy controls remained unchanged after taking probiotics suggesting that taking probiotics has no effect on the body’s physiological CRF.…”

Beneficial effects of the probiotics and synbiotics supplementation on anthropometric indices and body composition in adults: A systematic review and meta‐analysis

“…The general characteristics of the included studies are outlined in Table S4. Trials were published between 1996 and 2023, and were carried out in Asia, 12,27–31,77–81,84–229 Europe, 230–262 America,…”

Metabolic Status Influences Probiotic Efficacy for Depression—PRO-DEMET Randomized Clinical Trial Results

“…However, more participants were recruited considering the possible attrition rate. Due to significant difficulties in enrolling patients with MetS (as reported in the pilot study [31]), we decided to perform a two-arm study controlling for metabolic abnormalities.…”

“…Based on the above, the PRO-DEMET randomized controlled trial protocol was constructed [30]. Then, the pilot study was performed with convincing results regarding the feasibility of a whole-scale study [31]. Importantly, several alterations to the study plan were introduced and explained in the publication of the pilot study results, which are discussed throughout the current manuscript.…”