The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis

Abstract

Background: Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms.

Methods: We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect.

Results: Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit.

Interpretation: Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered.

Study registration: PROSPERO no. 143178.

Figure 1:

Flow diagram, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.

Figure 2:

Forest plot of (A) probiotic interventions in populations without depression, (B) probiotic interventions in populations with depression, prebiotic interventions in populations with and without depression, synbiotic interventions in populations with and without depression, and fecal microbiota transplant interventions in populations without depression. Note: BDI = Beck Depression Inventory, CAD = coronary artery disease, CES-D = Centre for Epidemiological Studies Depression Scale, CHD = coronary heart disease, CI = confidence interval, DASS21-D = Depression Anxiety and Stress Scales – 21 Items, Depression Scale, DASS42-D = Depression Anxiety Stress Scales – 42 Items, Depression Scale, DM = diabetes mellitus, EPDS = Edinburgh Postnatal Depression Scale, GDS-K = Geriatric Depression Scale – Korean Version, GDS-SF = Geriatric Depression Scale – Short Form, HADS-D = Hospital Anxiety and Depression Scale — Depression score, HAM-D = Hamilton Depression Rating Scale, IBS = irritable bowel syndrome, MADRS = Montgomery–Åsberg Depression Rating Scale, MDD = major depressive disorder, MI = myocardial infarction, MS = multiple sclerosis, PCOS = polycystic ovary syndrome, PHQ-9 = Patient Health Questionnaire – 9, SMD = standardized mean difference, TRD = treatment-resistant depression, Zung-SDS = Zung Self-Rating Depression Scale.

Figure 3:

Risk of bias for included studies, assessed with the Cochrane Risk of Bias tool, version 2.0.

Figure 4:

Funnel plots from trim and fill analysis of probiotic interventions in populations with depression, with (A) and without (B) study by Miyaoka et al., and of (C) probiotic and (D) synbiotic interventions in populations without depression.