Impact of probiotic supplementation on serum levels of brain-derived neurotrophic factor: GRADE-based dose-response meta-analysis.

2025-08-11
BMC nutrition 11(1)

PubMed: 40790243
DOI: 10.1186/s40795-025-01152-9

Study Design

Type: Systematic Review
Sample size: n = 2,372
Population: Randomized controlled trials (RCTs) involving adults (≥ 18 years) with reported BDNF levels
Methods: Systematic review and meta-analysis searching PubMed, Scopus, Cochrane Central, Web of Science, and Embase up to April 2025; included RCTs with a minimum 2-week probiotic intervention; random-effects model calculated weighted mean differences (WMDs), and fractional polynomial modeling assessed non-linear dose-response relationships

Abstract

Background: Brain-derived neurotrophic factor (BDNF) is a key neurotrophin involved in neuroplasticity and cognitive function, with its dysregulation linked to neurodegenerative and psychiatric disorders. Probiotics, through the gut-brain axis, may modulate BDNF levels, but evidence remains inconsistent. This meta-analysis aimed to evaluate the effect of probiotic supplementation on serum BDNF levels and explore dose-response relationships.

Methods: We conducted a systematic review and meta-analysis, searching PubMed, Scopus, Cochrane Central, Web of Science, and Embase up to April 2025, following PRISMA guidelines (PROSPERO: CRD420251036851). Randomized controlled trials (RCTs) involving adults (≥ 18 years) with a minimum 2-week probiotic intervention and reported BDNF levels were included. A random-effects model calculated weighted mean differences (WMDs), and fractional polynomial modeling assessed non-linear dose-response relationships. Heterogeneity, publication bias, and evidence quality (GRADE) were evaluated.

Results: From 20 RCTs (n = 2372 participants), probiotic supplementation significantly increased serum BDNF levels (WMD = 0.18, 95% CI: 0.11–0.26; P < 0.001), with high heterogeneity (I²=96%, P < 0.001). Subgroup analysis identified longer follow-up duration (> 10 weeks) as a heterogeneity source (WMD = 1.69, 95% CI: 1.13–2.26; I²=46%). A significant non-linear association was found between treatment duration and BDNF levels (Pnonlinearity = 0.02), but not dosage (Pnonlinearity = 0.277). No significant publication bias was detected (Begg’s P = 0.15; Egger’s P = 0.29). Evidence quality was very low per GRADE.

Conclusions: Probiotic supplementation increases serum BDNF levels, particularly with prolonged interventions (> 10 weeks), suggesting its potential as an adjunctive therapy for BDNF-related disorders, warranting further high-quality research.

Clinical trial number: Not applicable.

Supplementary Information: The online version contains supplementary material available at 10.1186/s40795-025-01152-9.

Keywords: Brain-derived neurotrophic factor; Gut-brain axis; Meta-analysis; Probiotic.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Bifidobacterium animalis subsp. lactis Bi-07	—	Increased Serum BDNF Levels	Beneficial	Small	View source “Probiotic supplementation significantly increased serum BDNF levels (WMD = 0.18, 95% CI: 0.11–0.26; P < 0.001)”
Bifidobacterium lactis Bi-07	—	Increased Serum BDNF Levels	Beneficial	Small	View source “Probiotic supplementation significantly increased serum BDNF levels (WMD = 0.18, 95% CI: 0.11–0.26; P < 0.001)”
Lactobacillus casei PXN 37	—	Increased Serum BDNF Levels	Beneficial	Small	View source “Probiotic supplementation significantly increased serum BDNF levels (WMD = 0.18, 95% CI: 0.11–0.26; P < 0.001)”
Lactobacillus rhamnosus PXN 54	—	Increased Serum BDNF Levels	Beneficial	Small	View source “Probiotic supplementation significantly increased serum BDNF levels (WMD = 0.18, 95% CI: 0.11–0.26; P < 0.001)”
Streptococcus thermophilus PXN 66	—	Increased Serum BDNF Levels	Beneficial	Small	View source “Probiotic supplementation significantly increased serum BDNF levels (WMD = 0.18, 95% CI: 0.11–0.26; P < 0.001)”