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Background <p>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.</p> Methods <p>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.</p> Results <p>From 20 RCTs (<i>n</i> = 2372 participants), probiotic supplementation significantly increased serum BDNF levels (WMD = 0.18, 95% CI: 0.11–0.26; <i>P</i> &lt; 0.001), with high heterogeneity (I²=96%, <i>P</i> &lt; 0.001). Subgroup analysis identified longer follow-up duration (&gt; 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 <i>P</i> = 0.15; Egger’s <i>P</i> = 0.29). Evidence quality was very low per GRADE.</p> Conclusions <p>Probiotic supplementation increases serum BDNF levels, particularly with prolonged interventions (&gt; 10 weeks), suggesting its potential as an adjunctive therapy for BDNF-related disorders, warranting further high-quality research.</p> Clinical trial number <p>Not applicable.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月11日

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  • Reza Hashemi,
  • Mohammad M. Hussein M. Raouf,
  • Tanya S. Salih,
  • Marzieh Feyzpour,
  • Maryam Eskandarioun,
  • Najmeh Nezamabadipour,
  • Hossein Gandomkar

摘要

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.