• The Effect of Pro-/Synbiotic Supplementation on Brain-Derived Neurotrophic Factor: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • Sahar Foshati,1,* Masoumeh Akhlaghi,2 Siavash Babajafari,3
    1. Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
    2. Department of Community Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
    3. Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran


  • Introduction: There is a growing interest in supplementation with pro-/synbiotics for brain and mental health. Animal studies have reported that pro-/synbiotic administration can increase brain-derived neurotrophic factor (BDNF), a key regulator of neuronal function. Nevertheless, the results obtained from human studies are inconsistent and conflicting. Therefore, we aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the impact of pro-/synbiotic supplementation on BDNF levels.
  • Methods: Scopus, Medline, Web of Science, Cochrane Library, and Google Scholar were searched up to July 10, 2022 to find eligible RCTs. The following Medical Subject Headings (MeSH) and non-MeSH terms were searched within keywords, abstracts, and titles: ("probiotics" OR "probiotic" OR "synbiotics" OR "synbiotic" OR "prebiotics" OR "prebiotic" OR "symbiotics" OR "symbiotic" OR "psychobiotics" OR "psychobiotic" OR "fermented" OR "Lactobacillus" OR "Bifidobacterium" OR "Saccharomyces" OR "Streptococcus" OR "Lactococcus" OR "Enterococcus" OR "Pediococcus" OR "Bacillus" OR "Leuconostoc" OR "Escherichia") AND ("brain-derived neurotrophic factor" OR "brain derived neurotrophic factor" OR "BDNF"). The weighted mean difference (WMD) and 95% confidence interval (CI) were computed for BDNF using a random-effects model.
  • Results: In the present study, 10 RCTs with 12 treatment arms consisting of 652 participants were included. The meta-analysis revealed that supplementation with pro-/synbiotics significantly increased BDNF concentrations in comparison with placebo (WMD: 0.20 ng/mL, 95% CI: 0.06 to 0.34, I2 = 86.6%). Moreover, subgroup analysis showed that target population, ethnicity and mean age of participants, number and type of probiotic strains, administration form, and dose and duration of pro-/synbiotic supplementation were potential sources of heterogeneity between RCTs.
  • Conclusion: In conclusion, pro-/synbiotic administration can be considered as a BDNF enhancer and possible brain booster.
  • Keywords: Probiotics, Synbiotics, Brain-derived neurotrophic factor, Systematic review, Meta-analysis