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

Abstract

Mounting evidence supports the concept of a microbiota-gut-brain axis and suggests that this axis is perturbed in neuropsychiatric disorders. The gut microbiota regulates host exposure to its products by modulating gut epithelial and blood-brain permeability, 1,2 both of which are altered in patients with major depressive disorder. [3][4][5][6] In addition, patients with major depressive dis order have shown substantial shifts in both the relative abun dance of taxa and the neuroactive metabolic potential of the gut microbiota, compared with healthy controls. [7][8][9][10][11][12] Because of this compelling preclinical data, 1-12 interven tions affecting the microbiota-gut-brain axis are a poten tial treatment modality for depressive symptoms. Multiple systematic reviews have been conducted to assess the effect of microbiotatargeting interventions on depressive symp toms, but they include diverse populations and different study designs, include different subsets of the interventions targeting the gut microbiota and, not surprisingly, report conflicting findings. [13][14][15] The objective of this study is to summarize the effect of microbiometargeting interven tions on depressive symptoms. Methods DesignWe conducted a systematic review and metaanalysis, following Cochrane recommendations for best practice, and the Pre ferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) for reporting. 16,17 We registered the proto col with PROSPERO (ID: 143178). As domain know ledge was refined, so too was the protocol and analysis strategy, in con sultation with domain experts; deviations from the registered protocol are outlined in Appendix 1, Section 1, available at www.cmajopen.ca/content/9/4/E1195/suppl/DC1. Briefly, we decided to focus on depressive symptoms, rather than all men tal health outcomes, to enhance interpretability.

Advances in the gut microbiome and mood disorders

“…Hofmeister et al [38 ▪▪ ] conducted a meta-analysis of 50 randomized controlled trials that showed that probiotic, prebiotic and synbiotic interventions had a statistically significant benefit, while faecal microbiota transplantation (FMT) and parabiotics (compounds that contain inactivated parts of probiotics) did not. Another recent meta-analysis published in 2022 by Sequeira et al [39 ▪▪ ] pointed out that, while probiotics overall did not seem to affect mood on a qualitative level, quantitative measures of depression and psychiatric distress improved slightly in individuals taking probiotics.…”

The Role of Psychobiotics to Ensure Mental Health during the COVID-19 Pandemic—A Current State of Knowledge

“…Administration of the 4-week multispecies probiotics intervention ( Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis W19 and W58) resulted in a significant reduction in overall cognitive reactivity to sad mood, which was largely accounted for by reduced rumination and aggressive thoughts [ 91 ]. To confirm the hypothesis that probiotics administration is associated with a significant reduction in depression, several systematic reviews and meta-analyses of the existing evidence were conducted [ 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. The evidence for probiotics alleviating depressive symptoms is compelling, which is confirmed by the secondary evidence found, but additional double-blind randomized control trials in clinical populations are necessitated to further assess efficacy.…”

Psychobiotics: a new way in psychopharmacology, or How do bacteria manage our brain?

“…Весьма впечатляют результаты метаанализа 50 ран домизированных контролируемых исследований, по священных влиянию вмешательств, направленных на микробиом (а именно применение пробиотиков, пребио тиков, синбиотиков или трансплантации фекальной ми кробиоты) на симптомы депрессии у пациентов в воз расте 18 лет и старше [125]. Применение пробиотиков, пребиотиков и синбиотиков при депрессивных симпто мах продемонстрировало статистически значимые улуч шения депрессии, в то время как ни в одном из еди ничных исследований по трансплантации фекальной микробиоты не было показано пользы [125].…”