Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2025, 169(2):91-97 | DOI: 10.5507/bp.2024.032

Serum neurofilament light chain in response to probiotics in bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota)

Lenka Fialova1, Ales Bartos2, Marta Kalousova1, Libuse Noskova1, Miroslava Zelenkova1, Michaela Slukova1, Tomas Zima1
1 Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia
2 Department of Neurology, Third Faculty of Medicine, Charles University, Faculty Hospital Kralovske Vinohrady, Prague, Czechia

Background and Aims: Neurodegenerative disorders affecting the brain and spinal cord are caused by a large number of factors. More recently, imbalances in gut microbiota are found to be one factor linked directly to neurological dysfunction. Probiotics prevent cognitive decline. For the first time, the effect of probiotics was assessed by monitoring the concentrations of the neurodegeneration biomarker neurofilament light chains (NfL) in a well-defined group of community-dwelling individuals. The aim of this study was to determine whether administration of our new probiotics could reduce NfL concentrations.

Methods: The serum NfL concentrations were measured in total of 190 serum samples of 85 older community-dwelling individuals. The participants were randomly divided into two groups: the PROPLA group and the PLAPRO group. Individuals in the PROPLA group started with a three-month use of probiotics and continued with a three-month use of placebo while the order was reversed in the PLAPRO group. The participants underwent detailed examinations at three time points: at baseline, in three and six months. The serum NfL concentrations were determined using ultrasensitive single-molecule array (SIMOA) assay.

Results: Longitudinal comparisons of NfL concentrations between samplings at different time points in the PROPLA and PLAPRO groups showed no statistically significant differences. Baseline NfL concentrations at the beginning of the study and in the succeeding samplings were not significantly different for the two groups in cross-sectional comparisons.

Conclusions: Serum NfL concentrations were not influenced by the three-month use of probiotics.

Keywords: serum, neurofilament light chain, probiotics, gastrointestinal microbiome, cognition

Received: June 26, 2024; Revised: August 23, 2024; Accepted: September 20, 2024; Prepublished online: October 14, 2024; Published: June 1, 2025  Show citation

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Fialova, L., Bartos, A., Kalousova, M., Noskova, L., Zelenkova, M., Slukova, M., & Zima, T. (2025). Serum neurofilament light chain in response to probiotics in bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota). Biomedical papers, 169(2), 91-97. doi: 10.5507/bp.2024.032
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    References

    1. . Chang C, Yuan X, Zhang X, Chen X, Li K. Gastrointestinal Microbiome and Multiple Health Outcomes: Umbrella Review. Nutrients 2022;14(18):3726. doi: 10.3390/nu14183726 Go to original source... Go to PubMed...
    2. . Un-Nisa A, Khan A, Zakria M, Siraj S, Ullah S, Tipu MK, Ikram M, Kim MO. Updates on the Role of Probiotics against Different Health Issues: Focus on Lactobacillus. Int J Mol Sci 2022;24(1):142. doi: 10.3390/ijms24010142 Go to original source... Go to PubMed...
    3. . Białecka-Dębek A, Granda D, Szmidt MK, Zielińska D. Gut Microbiota, Probiotic Interventions, and Cognitive Function in the Elderly: A Review of Current Knowledge. Nutrients 2021;13:2514. doi: 10.3390/nu13082514 Go to original source... Go to PubMed...
    4. . Drljača J, Miloąević N, Milanović M, Abenavoli L, Milić N. When the microbiome helps the brain-current evidence. CNS Neurosci Ther 2023;Suppl 1:43-58. doi: 10.1111/cns.14076 Go to original source... Go to PubMed...
    5. . Meng HYH, Mak CCH, Mak WY, Zuo T, Ko H, Chan FKL. Probiotic supplementation demonstrates therapeutic potential in treating gut dysbiosis and improving neurocognitive function in age-related dementia. Eur J Nutr 2022;61:1701-34. Go to original source... Go to PubMed...
    6. . 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 (Albany NY) 2020;12:4010-39. Go to original source... Go to PubMed...
    7. . Krüger JF, Hillesheim E, Pereira A, Camargo CQ, Rabito EI. Probiotics for dementia: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev 2021;79:160-70. Go to original source... Go to PubMed...
    8. . Tahmasbi F, Mirghafourvand M, Shamekh A, Mahmoodpoor A, Sanaie S. Effects of probiotic supplementation on cognitive function in elderly: A systematic review and Meta-analysis. Aging Ment Health 2022;26:1778-86. Go to original source... Go to PubMed...
    9. . Milajerdi A, Mousavi SM, Sadeghi A, Salari-Moghaddam A, Parohan M, Larijani B, Esmaillzadeh A. The effect of probiotics on inflammatory biomarkers: a meta-analysis of randomized clinical trials. Eur J Nutr 2020;59:633-49. Go to original source... Go to PubMed...
    10. . Vejux A. Cell Death, Inflammation and Oxidative Stress in Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules. Int J Mol Sci 2021;22:13657. doi: 10.3390/ijms222413657 Go to original source... Go to PubMed...
    11. . Bartos A, Fialova L, Soukupova J, Kukal J, Malbohan I, Pitha J. Antibodies against light neurofilaments in multiple sclerosis patients. Acta Neurol Scand 2007;116:100-7. Go to original source... Go to PubMed...
    12. . Bartos A, Fialova L, Svarcova J. Lower Serum Antibodies Against Tau Protein and Heavy Neurofilament in Alzheimer's Disease. J Alzheimers Dis 2018;64(3):751-60. doi: 10.3233/JAD-180039 Go to original source... Go to PubMed...
    13. . Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE, Alvarez-Cermeño JC, Andreasson U, Axelsson M, Bäckström DC, Bartos A, Bjerke M, Blennow K, Boxer A, Brundin L, Burman J, Christensen T, Fialová L, Forsgren L, Frederiksen JL, Gisslén M, Gray E, Gunnarsson M, Hall S, Hansson O, Herbert MK, Jakobsson J, Jessen-Krut J, Janelidze S, Johannsson G, Jonsson M, Kappos L, Khademi M, Khalil M, Kuhle J, Landén M, Leinonen V, Logroscino G, Lu CH, Lycke J, Magdalinou NK, Malaspina A, Mattsson N, Meeter LH, Mehta SR, Modvig S, Olsson T, Paterson RW, Pérez-Santiago J, Piehl F, Pijnenburg YAL, Pyykkö OT, Ragnarsson O, Rojas JC, Romme Christensen J, Sandberg L, Scherling CS, Schott JM, Sellebjerg FT, Simone IL, Skillbäck T, Stilund M, Sundström P, Svenningsson A, Tortelli R, Tortorella C, Trentini A, Troiano M, Turner MR, van Swieten JC, Vågberg M, Verbeek MM, Villar LM, Visser PJ, Wallin A, Weiss A, Wikkelsø C, Wild EJ. Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis. JAMA Neurol 2019;76:1035-48. doi: 10.1001/jamaneurol.2019.1534 Go to original source... Go to PubMed...
    14. . Buchmann A, Pirpamer L, Pinter D, Voortman M, Helmlinger B, Pichler A, Maceski AM, Benkert P, Bachmaier G, Ropele S, Reindl M, Leppert D, Kuhle J, Enzinger C, Khalil M. High serum neurofilament light chain levels correlate with brain atrophy and physical disability in multiple sclerosis. Eur J Neurol 2023;30:1389-99. Go to original source... Go to PubMed...
    15. . Fialova L, Svarcova J, Bartos A, Ridzon P, Malbohan I, Keller O, Rusina R. Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosis. Eur J Neurol 2010;17:562-6. Go to original source... Go to PubMed...
    16. . Fialova L, Bartos A, Svarcova J, Zimova D, Kotoucova J, Malbohan I. Serum and cerebrospinal fluid light neurofilaments and antibodies against them in clinically isolated syndrome and multiple sclerosis. J Neuroimmunol 2013;262:113-20. Go to original source... Go to PubMed...
    17. . Fang T, Dai Y, Hu X, Xu Y, Qiao J. Evaluation of serum neurofilament light chain and glial fibrillary acidic protein in the diagnosis of Alzheimer's disease. Front Neurol 2024;30;15:1320653. doi: 10.3389/fneur.2024.132065 Go to original source...
    18. . Fialová L, Nosková L, Kalousová M, Zima T, Uher T, Bartoą A. Analytical and pre-analytical aspects of neurofilament light chain determination in biological fluids. Cesk Slov Neurol N 2022;85:11-6. (In Czech) Go to original source...
    19. . Gordon BA. Neurofilaments in disease: what do we know? Curr Opin Neurobiol 2020;61:105-15. Go to original source... Go to PubMed...
    20. . Papuć E, Rejdak K. Increased CSF NFL in Non-demented Parkinson's Disease Subjects Reflects Early White Matter Damage. Front Aging Neurosci 2020;12:128. doi: 10.3389/fnagi.2020.00128 Go to original source... Go to PubMed...
    21. . Sapko K, Jamroz-Wi¶niewska A, Marciniec M, Kulczyński M, Szczepańska-Szerej A, Rejdak K. Biomarkers in Multiple Sclerosis: a review of diagnostic and prognostic factors. Neurol Neurochir Pol 2020;54:252-8. Go to original source... Go to PubMed...
    22. . Taghdiri F, Multani N, Ozzoude M, Tarazi A, Khodadadi M, Wennberg R, Mikulis D, Green R, Colella B, Davis KD, Blennow K, Zetterberg H, Tator C, Tartaglia MC. Neurofilament-light in former athletes: a potential biomarker of neurodegeneration and progression. Eur J Neurol 2020;27:1170-7. Go to original source... Go to PubMed...
    23. . Revendova KZ, Zeman D, Bunganic R, Karasova K, Volny O, Bar M and Kusnierova P. Serum neurofilament levels in patients with multiple sclerosis: A comparison of SIMOA and high sensitivity ELISA assays and contributing factors to ELISA levels. Mult Scler Relat Disord 2022;67:104177. doi: 10.1016/j.msard.2022.104177 Go to original source... Go to PubMed...
    24. . Jung Y, Damoiseaux JS. The potential of blood neurofilament light as a marker of neurodegeneration for Alzheimer's disease. Brain 2024;147:12-25. Go to original source... Go to PubMed...
    25. . Bartos A, Krejcova M. Validation of the electronic memory test ALBAV. Cesk Slov Neurol N 2023;86:49-56. (In Czech) Go to original source...
    26. . Bartos A, Weinerova J, Diondet S, Vales K. Effect of human probiotics on memory, psychological and biological measures in elderly: A study protocol of bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota). Front Aging Neurosci 2022;14:996234. doi: 10.3389/fnagi.2022.996234 Go to original source... Go to PubMed...
    27. . Bartos A, Krejcova M. Development of the electronic memory test for the elderly (ALBAV). Cesk Slov Neurol N 2022;85:369-74. (In Czech) Go to original source...
    28. . Vermunt L, Otte M, Verberk IMW, Killestein J, Lemstra AW, van der Flier WM, Pijnenburg YAL, Vijverberg EGB, Bouwman FH, Gravesteijn G, van de Berg WDJ, Scheltens P, van Harten AC, Willemse EAJ, Teunissen CE. Age- and disease-specific reference values for neurofilament light presented in an online interactive support interface. Ann Clin Transl Neurol 2022;9:1832-7. Go to original source... Go to PubMed...
    29. . Bartos A, Weinerova J, Diondet S. Effects of human probiotics on memory and psychological and physical measures in community-dwelling older adults with normal and mildly impaired cognition: results of a bi-center, double-blind, randomized, and placebo-controlled clinical trial (CleverAge biota). Front Aging Neurosci 2023;15:1163727. doi: 10.3389/fnagi.2023.1163727 Go to original source... Go to PubMed...
    30. . Barro C, Chitnis T, Weiner HL. Blood neurofilament light: a critical review of its application to neurologic disease. Ann Clin Transl Neurol 2020;7:2508-23. Go to original source... Go to PubMed...
    31. . Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry 2019;90:870-81. Go to original source... Go to PubMed...
    32. . Kapoor M, Carr A, Foiani M, Heslegrave A, Zetterberg H, Malaspina A, Compton L, Hutton E, Rossor A, Reilly MM, Lunn MP. Association of plasma neurofilament light chain with disease activity in chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol 2022;29:3347-57. Go to original source... Go to PubMed...
    33. . Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 2018;14:577-89. Go to original source... Go to PubMed...
    34. . Salvadores N, Sanhueza M, Manque P, Court FA. Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders. Front Neurosci 2017;11:451. doi: 10.3389/fnins.2017.00451 Go to original source... Go to PubMed...
    35. . Zhao Y, Arceneaux L, Culicchia F, Lukiw WJ. Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery. HSOA J Alzheimers Neurodegener Dis 2021;7(2):056. doi: 10.24966/and-9608/100056 Go to original source... Go to PubMed...
    36. . Fialová L. Neurofilaments in traumatic brain injury - current knowledge. Klin Biochem Metab 2018;26,68-75. (In Czech) Go to original source...
    37. . Uher T, Adzima A, Srpova B, Noskova L, Maréchal B, Maceski AM, Krasensky J, Stastna D, Andelova M, Novotna K, Vodehnalova K, Motyl J, Friedova L, Lindner J, Ravano V, Burgetova A, Dusek P, Fialova L, Havrdova EK, Horakova D, Kober T, Kuhle J, Vaneckova M. Diagnostic delay of multiple sclerosis: prevalence, determinants and consequences. Mult Scler 2023;29(11-12):1437-51. Go to original source... Go to PubMed...
    38. . Novobilský R, Bartova P, Lichá K, Bar M, Stejskal D, Kusnierova P. Serum neurofilament light chain levels in patients with cognitive deficits and movement disorders: comparison of cerebrospinal and serum neurofilament light chain levels with other biomarkers. Front Hum Neurosci 2023;17:1284416. doi: 10.3389/fnhum.2023.1284416 Go to original source... Go to PubMed...
    39. . Kuąnierová P, Zeman D, Hradílek P, Čábal M, Zapletalová O. Neurofilament levels in patients with neurological diseases: A comparison of neurofilament light and heavy chain levels. J Clin Lab Anal 2019;33:e22948. doi: 10.1002/jcla.22948 Go to original source... Go to PubMed...
    40. . Kaiserova M, Grambalova Z, Otruba P, Stejskal D, Prikrylova Vranova H, Mares J, Mensikova K, Kanovsky P. Cerebrospinal fluid levels of chromogranin A and phosphorylated neurofilament heavy chain are elevated in amyotrophic lateral sclerosis. Acta Neurol Scand 2017;136:360-4. Go to original source... Go to PubMed...
    41. . Mitra S, Dash R, Nishan AA, Habiba SU, Moon IS. Brain modulation by the gut microbiota: From disease to therapy. J Adv Res 2023;53:153-73. Go to original source... Go to PubMed...

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