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.