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Meta-Analysis
. 2025 Jan 21;25(1):64.
doi: 10.1186/s12888-024-06438-z.

Efficacy and safety of gut microbiome-targeted treatment in patients with depression: a systematic review and meta-analysis

Bo Pan #  1   2 , Yiming Pan #  1   2 , Yu-Song Huang #  3 , Meng Yi  1 , Yuwei Hu  1   2 , Xiaoyu Lian  1   2 , Hui-Zhong Shi  4 , Mingwei Wang  1   2 , Guifen Xiang  1   2   5 , Wen-Yi Yang  6 , Zhong Liu  7   8   9 , Fangfang Xia  10
Affiliations
Meta-Analysis

Efficacy and safety of gut microbiome-targeted treatment in patients with depression: a systematic review and meta-analysis

Bo Pan et al. BMC Psychiatry. .

Abstract

Background: The study aimed to comprehensively analyze and establish a framework for evaluating the efficacy of microbiome-targeted treatment (MTT) for depression.

Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, and the Chinese National Knowledge Infrastructure database for randomized controlled trials (RCTs) on MTT in treating depression until October 19, 2023. A meta-analysis was conducted to evaluate the efficacy and safety of MTT. Comprehensive subgroup analyses were undertaken to explore factors influencing MTT's efficacy in treating depression. This study was registered with PROSPERO (CRD42023483649).

Results: The study selection process identified 51,570 studies, of which 34 met the inclusion criteria. The overall pooled estimates showed that MTT significantly improved depression symptoms (SMD -0.26, 95% CI [-0.32, -0.19], I2 = 54%) with acceptable safety. Subgroup analyses by geography showed that effectiveness was demonstrated in Asia (SMD -0.46, 95% CI [-0.56, -0.36], I2 = 36%), while no evidence of effectiveness was found in Europe (SMD -0.07, 95% CI [-0.19, 0.05], I2 = 55%), America (SMD -0.33, 95% CI [-0.67, 0.02], I2 = 60%), and Oceania (SMD 0.00, 95% CI [-0.18, 0.18], I2 = 0%). Besides, the efficacy was shown in depressed patients without comorbidities (SMD -0.31, 95% CI [-0.40, -0.22], I2 = 0%), whereas effectiveness was poor in those with digestive disorders, such as irritable bowel syndrome (SMD -0.37, 95% CI [-0.89, 0.16], I2 = 74%), chronic diarrhea (SMD -0.34, 95% CI [-0.73, 0.05]), and chronic constipation (SMD -0.23, 95% CI [-0.57, 0.11], I2 = 0%). In perinatal depressed patients, MTT was not effective (SMD 0.16, 95% CI [0.01, 0.31], I2 = 0%). It was found that < 8 weeks (SMD -0.33, 95% CI [-0.45, -0.22], I2 = 0%) and 8-12 weeks (SMD -0.34, 95% CI [-0.44, -0.23], I2 = 57%) MTT were effective, while > 12 weeks (SMD 0.02, 95% CI [-0.12, 0.17], I2 = 68%) MTT was ineffective.

Conclusions: Despite the overall effectiveness of MTT in treating depression and its acceptable safety profile, caution is warranted in drawing this conclusion due to limitations posed by the small sample size of included studies and heterogeneity. The efficacy of MTT for depression exhibits variation influenced by geography, patient comorbidities, and duration of administration.

Keywords: Depression; Geographical region; Meta-analysis; Microbiome–targeted therapy; Patient characteristics; Precision medicine.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Global RCTs on MTT for depression
Fig. 2
Fig. 2
Assessment for risk of bias in included studies
Fig. 3
Fig. 3
The overall pooled estimates of MTT efficacy for depression
Fig. 4
Fig. 4
Forest plot of biochemical indices modulated by MTT in patients with depression
Fig. 5
Fig. 5
Subgroup analysis of different administration durations of MTT for depression
Fig. 6
Fig. 6
Subgroup analysis of different continents and demography
Fig. 7
Fig. 7
Subgroup analysis of the MTT efficacy for depressed patients with comorbidities or not
Fig. 8
Fig. 8
The effect of MTT treatment on adverse reactions
Fig. 9
Fig. 9
Results of sensitivity analysis using the one-by-one exclusion method. The numerical order corresponds to the order of study in Fig. 3
Fig. 10
Fig. 10
The graphical overview of MTT efficacy in treating depression. Created on BioRender.com
See this image and copyright information in PMC

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