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

  • Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications, (in eng). Arch Med Sci. Dec 10 2015;11(6):1164–78. https://doi.org/10.5114/aoms.2015.56342

  • Burovenko IY, Borshchev YY, Minasyan SM, Protsak ES, Borshcheva OV, Galagudza MM. Brain-Derived neurotrophic factor cancels the cardioprotective effect of Interleukin-2 in a model of systemic inflammatory response in rats, (in eng). Bull Exp Biol Med Apr. 2025;29. https://doi.org/10.1007/s10517-025-06377-z

  • Ginelli E et al. Impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor levels in treatment-resistant depression, (in eng), Front Psychiatry, 2025;16:1584673, https://doi.org/10.3389/fpsyt.2025.1584673

  • Yuping Z, Tianbi L, Wentao S, Yun L, Guodong Z. The Optimal Type and Dose of Exercise for Elevating Brain-Derived Neurotrophic Factor Levels in Patients With Depression: A Systematic Review With Pairwise, Network, and Dose-Response Meta-Analyses, (in eng), Depress Anxiety, 2024;2024:5716755. https://doi.org/10.1155/da/5716755

  • Cho CY et al. Exploring the prospective association of serum interleukin-1β and brain-derived neurotrophic factor with antidepressant treatment response, (in eng), Eur Neuropsychopharmacol, 2025;95:33–39, https://doi.org/10.1016/j.euroneuro.2025.03.004

  • Miranda M, Morici JF, Zanoni MB, Bekinschtein P. Brain-Derived neurotrophic factor: A key molecule for memory in the healthy and the pathological brain, (in eng). Front Cell Neurosci. 2019;13:363. https://doi.org/10.3389/fncel.2019.00363

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota, (in eng), J Clin Invest, 2015;125(3):926 – 38,, https://doi.org/10.1172/jci76304

  • Gandomkar H, Mahmoodzadeh H, Tavakoli H, Fazeli M, Rezaei J. Garlic-induced esophageal perforation: A case series, (in eng). Asian J Surg. Jun 2020;43(6):696–7. https://doi.org/10.1016/j.asjsur.2020.01.002

  • Morvaridi M, Rayyani E, Jaafari M, Khiabani A, Rahimlou M. The effect of green coffee extract supplementation on cardio metabolic risk factors: a systematic review and meta-analysis of randomized controlled trials, (in eng). J Diabetes Metab Disord. Jun 2020;19(1):645–60. https://doi.org/10.1007/s40200-020-00536-x

  • Hill C et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic, (in eng), Nat Rev Gastroenterol Hepatol, 2014;11(8):506 – 14, https://doi.org/10.1038/nrgastro.2014.66

  • Talebi S et al. The Association between Total Protein, Animal Protein, and Animal Protein Sources with Risk of Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Cohort Studies, (in eng), Adv Nutr, 2023;14(4):752–761, https://doi.org/10.1016/j.advnut.2023.05.008

  • Mousavi SN, Rayyani E, Heshmati J, Tavasolian R, Rahimlou M. Effects of ramadan and non-ramadan intermittent fasting on gut Microbiome. Front Nutr. 2022;9:860575.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Savignac HM et al. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine, (in eng), Neurochem Int, 2013;63(8):756 – 64, https://doi.org/10.1016/j.neuint.2013.10.006

  • Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review, (in eng). Ann Gen Psychiatry. 2017;16:14. https://doi.org/10.1186/s12991-017-0138-2

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Abdollahi H, et al. The biochemical parameters and vitamin D levels in ICU patients with Covid-19: A Cross-Sectional study, (in eng). Endocr Metab Immune Disord Drug Targets. 2021;21(12):2191–202. https://doi.org/10.2174/1871530321666210316103403

    Article 
    PubMed 

    Google Scholar 

  • Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials, (in eng). Neurosci Biobehav Rev. Jul 2019;102:13–23. https://doi.org/10.1016/j.neubiorev.2019.03.023

  • Ng QX, Peters C, Ho CYX, Lim DY, Yeo WS. A meta-analysis of the use of probiotics to alleviate depressive symptoms, (in eng), J Affect Disord, 2018;228:13–19, https://doi.org/10.1016/j.jad.2017.11.063

  • McKean J, Naug H, Nikbakht E, Amiet B, Colson N. Probiotics and subclinical psychological symptoms in healthy participants: A systematic review and Meta-Analysis, (in eng). J Altern Complement Med. Apr 2017;23(4):249–58. https://doi.org/10.1089/acm.2016.0023

  • Abdollahi H et al. Evaluation of depression, anxiety and stress scores in patients with Covid-19: A Cross-Sectional study. Archives Anesth Crit Care, 2024;10:15–26

  • Dehghani F, Abdollahi S, Shidfar F, Clark CC, Soltani S. Probiotics supplementation and brain-derived neurotrophic factor (BDNF): A systematic review and meta-analysis of randomized controlled trials. Nutr Neurosci. 2023;26(10):942–52.

    PubMed 

    Google Scholar 

  • Vakilzadehian N, et al. Non-coding RNA in the regulation of gastric cancer tumorigenesis: focus on MicroRNAs and Exosomal MicroRNAs, (in eng). Int J Mol Cell Med. 2024;13(4):417–35. https://doi.org/10.22088/ijmcm.Bums.13.4.417

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kar F, Hacioglu C, Kar E, Donmez DB, Kanbak G. Probiotics ameliorates LPS induced neuroinflammation injury on Aβ 1–42, APP, γ-β secretase and BDNF levels in maternal gut microbiota and fetal neurodevelopment processes. Metab Brain Dis. 2022;37(5):1387–99.

    PubMed 

    Google Scholar 

  • Schneider E et al. Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial. J Psychiatry Neurosci, 2023;48(1):E23-E33.

  • Hsu Y-C et al. Efficacy of probiotic supplements on brain-derived neurotrophic factor, inflammatory biomarkers, oxidative stress and cognitive function in patients with Alzheimer’s dementia: A 12-week randomized, double-blind active-controlled study, Nutrients, 2023;16(1):16.

  • Page MJ et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews, bmj, 2021;372.

  • Sterne JA et al. RoB 2: a revised tool for assessing risk of bias in randomised trials, bmj, 2019;366.

  • Mansournia MA, Higgins JP, Sterne JA, Hernán MA. Biases in randomized trials: a conversation between trialists and epidemiologists, Epidemiology, 2017;28(1):54–59.

  • Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:1–10.

    Google Scholar 

  • Rosenblad A, Hedges LV, Julian PT, Higgins HR, Rothstein. Int Stat Rev. 2009;77(3):478–9.

    Google Scholar 

  • Brondani LA, Assmann TS, de Souza BM, Boucas AP, Canani LH, Crispim D. Meta-analysis reveals the association of common variants in the uncoupling protein (UCP) 1–3 genes with body mass index variability. PLoS ONE. 2014;9(5):e96411.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Zahedi H, et al. Dietary inflammatory potential score and risk of breast cancer: systematic review and meta-analysis. Clin Breast Cancer. 2018;18(4):e561–70.

    PubMed 

    Google Scholar 

  • Tobias A. Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull. 1999;47:15–7.

    Google Scholar 

  • Lee HJ et al. Jul 30., Effects of probiotic NVP-1704 on mental health and sleep in healthy adults: an 8-Week randomized, Double-Blind, Placebo-Controlled trial, (in eng), Nutrients, 2021;13(8), https://doi.org/10.3390/nu13082660

  • Önning G, Montelius C, Hillman M, Larsson N. Aug 5, Intake of Lactiplantibacillus plantarum HEAL9 improves cognition in moderately stressed subjects: A randomized controlled study, (in eng), Nutrients, 2023;15(15), https://doi.org/10.3390/nu15153466

  • Heidarzadeh-Rad N, Gökmen-Özel H, Kazemi A, Almasi N, Djafarian K. Effects of a Psychobiotic Supplement on Serum Brain-derived Neurotrophic Factor Levels in Depressive Patients: A Post Hoc Analysis of a Randomized Clinical Trial, (in eng), J Neurogastroenterol Motil, 2020;26(4):486–495, https://doi.org/10.5056/jnm20079

  • Kato-Kataoka A et al. Fermented Milk Containing Lactobacillus casei Strain Shirota Preserves the Diversity of the Gut Microbiota and Relieves Abdominal Dysfunction in Healthy Medical Students Exposed to Academic Stress, (in eng), Appl Environ Microbiol, 2016;82(12):3649-58. https://doi.org/10.1128/aem.04134-15

  • Hwang YH et al. Efficacy and Safety of Lactobacillus Plantarum C29-Fermented Soybean (DW2009) in Individuals with Mild Cognitive Impairment: A 12-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial, (in eng), Nutrients, 2019;11(2), https://doi.org/10.3390/nu11020305

  • Kim CS, et al. Probiotic supplementation improves cognitive function and mood with changes in gut microbiota in Community-Dwelling older adults: A randomized, Double-Blind, Placebo-Controlled, multicenter trial, (in eng). J Gerontol Biol Sci Med Sci. Jan 1 2021;76(1):32–40. https://doi.org/10.1093/gerona/glaa090

  • Pinto-Sanchez MI et al. Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome, (in eng), Gastroenterology, 2017;153(2):448–459.e8, https://doi.org/10.1053/j.gastro.2017.05.003

  • Riezzo G, Chimienti G, Orlando A, D’Attoma B, Clemente C, Russo F. Effects of long-term administration of Lactobacillus reuteri DSM-17938 on Circulating levels of 5-HT and BDNF in adults with functional constipation, (in eng). Benef Microbes, 10, 2, pp. 137–47, Mar 13 2019, https://doi.org/10.3920/bm2018.0050

  • Romijn AR, Rucklidge JJ, Kuijer RG, Frampton C. A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and bifidobacterium longum for the symptoms of depression, (in eng). Aust N Z J Psychiatry. Aug 2017;51(8):810–21. https://doi.org/10.1177/0004867416686694

  • Tomasik J, Yolken RH, Bahn S, Dickerson FB. Immunomodulatory Effects of Probiotic Supplementation in Schizophrenia Patients: A Randomized, Placebo-Controlled Trial, (in eng), Biomark Insights, 2015;10:47–54, https://doi.org/10.4137/bmi.S22007

  • West NP et al. Supplementation with a single and double strain probiotic on the innate immune system for respiratory illness, e-SPEN Journal, Article 2014;9(5):e178-e184, https://doi.org/10.1016/j.clnme.2014.06.003

  • Elahinejad V et al. Effects of Probiotics as Adjunctive Therapy to Fluoxetine on Depression Severity and Serum Brain-Derived Neurotrophic Factor, Cortisol, and Adrenocorticotropic Hormone in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial, (in eng), Food Sci Nutr, 2025;13(4):e4698, https://doi.org/10.1002/fsn3.4698

  • Climent E et al. Psychobiotic Protection of Nutritional Supplements and Probiotics in Patients Undergoing Hemodialysis: A Randomized Trial, (in eng), Nutrients, 2025;17(4), https://doi.org/10.3390/nu17040652

  • Nikolova VL, Cleare AJ, Young AH, Stone JM. Exploring the mechanisms of action of probiotics in depression: results from a randomized controlled pilot trial. J Affect Disord, 376, pp. 241–50, 2025/05/01/ 2025, https://doi.org/10.1016/j.jad.2025.01.153

  • Nisaa A et al. Probiotic enhanced immunity and mental wellbeing of generally healthy women: a randomised, placebo-controlled and double-blind study, Beneficial Microbes, 2025;1(aop):1–18.

  • Fan Q et al. Weizmannia coagulans BC99 Relieves Constipation Symptoms by Regulating Inflammatory, Neurotransmitter, and Lipid Metabolic Pathways: A Randomized, Double-Blind, Placebo-Controlled Trial, (in eng), Foods, 2025;14(4), https://doi.org/10.3390/foods14040654

  • Suzuki T et al. The effects of Mold-Fermented cheese on Brain-Derived neurotrophic factor in Community-Dwelling older Japanese women with mild cognitive impairment: A randomized, controlled, crossover trial. J Am Med Dir Assoc, 20, 12, pp. 1509–14.e2, 2019/12/01/ 2019, https://doi.org/10.1016/j.jamda.2019.06.023

  • Huang W, et al. Efficacy of electroacupuncture combined with probiotics for depression and chronic diarrhea in patients and effect on serum inflammatory cytokines, NE and BDNF, (in eng). Exp Ther Med. Nov 2019;18(5):3470–4. https://doi.org/10.3892/etm.2019.7977

  • Haghighat N, Rajabi S, Mohammadshahi M. Effect of synbiotic and probiotic supplementation on serum brain-derived neurotrophic factor level, depression and anxiety symptoms in hemodialysis patients: a randomized, double-blinded, clinical trial, (in eng), Nutr Neurosci, 2021;24(6):490–499, https://doi.org/10.1080/1028415x.2019.1646975

  • Rahimlou M, Hosseini SA, Majdinasab N, Haghighizadeh MH, Husain D. Effects of long-term administration of Multi-Strain Probiotic on circulating levels of BDNF, NGF, IL-6 and mental health in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled trial, (in eng), Nutr Neurosci, 2022;25(2):411–422, https://doi.org/10.1080/1028415x.2020.1758887

  • Ruiz-Gonzalez C, Cardona D, Rueda-Ruzafa L, Rodriguez-Arrastia M, Ropero-Padilla C, Roman P. Cognitive and emotional effect of a Multi-species probiotic containing Lactobacillus rhamnosus and bifidobacterium lactis in healthy older adults: A Double-Blind randomized Placebo‐Controlled crossover trial. Probiotics Antimicrob Proteins, 2024;13:1–13.

  • Mörkl S, Butler MI, Holl A, Cryan JF, Dinan TG. Probiotics and the microbiota-gut-brain axis: focus on psychiatry. Curr Nutr Rep. 2020;9:171–82.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Hashemi R, Mehdizadeh Khalifani A, Rahimlou M, Manafi M. Comparison of the effect of dietary approaches to stop hypertension diet and American diabetes association nutrition guidelines on lipid profiles in patients with type 2 diabetes: A comparative clinical trial, (in eng). Nutr Diet. Apr 2020;77(2):204–11. https://doi.org/10.1111/1747-0080.12543

  • Den H, Dong X, Chen M, Zou Z. Efficacy of probiotics on cognition, and biomarkers of inflammation and oxidative stress in adults with alzheimer’s disease or mild cognitive impairment—A meta-analysis of randomized controlled trials. Aging. 2020;12(4):4010.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhu G, Zhao J, Zhang H, Chen W, Wang G. Probiotics for mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis, Foods, 2021;10(7):1672.

  • Rafati A, et al. Association of SARS-CoV-2 vaccination or infection with bell palsy: A systematic review and Meta-analysis, (in eng). JAMA Otolaryngol Head Neck Surg. Jun 1 2023;149(6):493–504. https://doi.org/10.1001/jamaoto.2023.0160

  • Ameri A, et al. A review of the progress and challenges of developing dendritic-based vaccines against hepatitis B virus (HBV), (in eng). Pathol Res Pract. Jul 2025;271:156025. https://doi.org/10.1016/j.prp.2025.156025

  • Keshavarz Z, et al. Non-alcoholic fatty liver disease and dairy products consumption: results from FASA Persian cohort study, (in eng). Front Nutr. 2022;9:962834. https://doi.org/10.3389/fnut.2022.962834

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Westfall S, Lomis N, Kahouli I, Dia SY, Singh SP, Prakash S. Microbiome, probiotics and neurodegenerative diseases: Deciphering the gut brain axis. Cell Mol Life Sci. 2017;74:3769–87.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Habibi MA et al. The effect of radiotherapy on patients with EGFR-driven lung cancer brain metastasis: a systematic review and meta-analysis, (in eng), Discov Oncol, 2025;16(1):1023, https://doi.org/10.1007/s12672-025-02780-0

  • Radford-Smith DE, Anthony DC. Prebiotic and probiotic modulation of the microbiota–gut–brain axis in depression, Nutrients, 2023;15(8):1880.

  • Xiao J, et al. Probiotic bifidobacterium Breve in improving cognitive functions of older adults with suspected mild cognitive impairment: a randomized, double-blind, placebo-controlled trial. J Alzheimer’s Disease. 2020;77(1):139–47.

    Google Scholar 

  • Liu N, Yang D, Sun J, Li Y. Probiotic supplements are effective in people with cognitive impairment: a meta-analysis of randomized controlled trials. Nutr Rev. 2023;81(9):1091–104.

    PubMed 

    Google Scholar 

  • Frank MG, Fonken LK, Watkins LR, Maier SF, Lowry CA. Could probiotics be used to mitigate neuroinflammation? ACS Chem Neurosci. 2018;10(1):13–5.

    PubMed 

    Google Scholar 

  • Yu W, et al. Probiotics alleviate cognitive dysfunction associated with neuroinflammation in cardiac surgery. Am J Translational Res. 2019;11(12):7614.

    Google Scholar 

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