The Effects of a Novel Supplement Containing Probiotics and Vitamin D as an Adjutant Therapy on sNFL and Th Cell Profiles in Patients with Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial

Patejdl R, Penner IK, Noack TK, Zettl UK. Multiple sclerosis and fatigue: a review on the contribution of inflammation and immune-mediated neurodegeneration. Autoimmun Rev Elsevier. 2016;15:210–20.

Article  CAS  Google Scholar 

Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J. Royan Institute; 2017;19:1.

Palle P, Monaghan KL, Milne SM, Wan ECK. Cytokine signaling in multiple sclerosis and its therapeutic applications. Med Sci. MDPI; 2017;5:23.

Cicchese JM, Evans S, Hult C, Joslyn LR, Wessler T, Millar JA, et al. Dynamic balance of pro and anti inflammatory signals controls disease and limits pathology. Immunol Rev. 2018;285:147–67.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine Elsevier. 2015;74:5–17.

Article  CAS  Google Scholar 

Hoglund RA, Maghazachi AA. Multiple sclerosis and the role of immune cells. World J Exp Med. Baishideng Publishing Group Inc; 2014;4:27.

Duhen R, Glatigny S, Arbelaez CA, Blair TC, Oukka M, Bettelli E. Cutting edge: the pathogenicity of IFN-γ-producing Th17 cells is independent of T-bet. J Immunol. 2013;190(9):4478–82. https://doi.org/10.4049/jimmunol.1203172.

Article  CAS  PubMed  Google Scholar 

Konig J, Wells J, Cani PD, Garcia-Rodenas CL, MacDonald T, Mercenier A, et al. Human intestinal barrier function in health and disease. Clin Transl Gastroenterol. American College of Gastroenterology; 2016;7:e196.

Ostadmohammadi V, Jamilian M, Bahmani F, Asemi Z. Vitamin D and probiotic co-supplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome. J Ovarian Res BioMed Central. 2019;12:1–8.

Google Scholar 

Chen J, Wang L, Xu H, Wang Y, Liang Q. The lymphatic drainage system of the CNS plays a role in lymphatic drainage, immunity, and neuroinflammation in stroke. J Leukoc Biol Oxford University Press. 2021;110:283–91.

Article  CAS  Google Scholar 

Moraes AS, Boldrini VO, Dionete AC, Andrade MD, Longhini ALF, Santos I, et al. Decreased Neurofilament L Chain Levels in Cerebrospinal Fluid and Tolerogenic Plasmacytoid Dendritic Cells in Natalizumab-Treated Multiple Sclerosis Patients-Brief Research Report. Front Cell Neurosci. Frontiers; 2021;270.

Ferreira-Atuesta C, Reyes S, Giovanonni G, Gnanapavan S. The evolution of neurofilament light chain in multiple sclerosis. Front Neurosci. Frontiers Media SA; 2021;15:642384.

Westerberg LS, Klein C, Snapper SB. Breakdown of T cell tolerance and autoimmunity in primary immunodeficiency-lessons learned from monogenic disorders in mice and men. Curr Opin Immunol Elsevier. 2008;20:646–54.

Article  CAS  Google Scholar 

Moser T, Akgun K, Proschmann U, Sellner J, Ziemssen T. The role of TH17 cells in multiple sclerosis: Therapeutic implications. Autoimmun Rev. Elsevier; 2020;19:102647.

Rocamora-Reverte L, Melzer FL, Wurzner R, Weinberger B. The complex role of regulatory T cells in immunity and aging. Front Immunol. Frontiers Media SA; 2021;11:616949.

Schepici G, Silvestro S, Bramanti P, Mazzon E. The gut microbiota in multiple sclerosis: an overview of clinical trials. Cell Transplant. Sage Publications Sage CA: Los Angeles, CA; 2019;28:1507–27.

Schirmer M, Smeekens SP, Vlamakis H, Jaeger M, Oosting M, Franzosa EA, et al. Linking the human gut microbiome to inflammatory cytokine production capacity. Cell Elsevier. 2016;167:1125–36.

Article  CAS  Google Scholar 

Zhou X, Baumann R, Gao X, Mendoza M, Singh S, Sand IK, et al. Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course. Cell Elsevier. 2022;185:3467–86.

Article  Google Scholar 

Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. SAGE Publications Sage UK: London, England; 2013;6:39–51.

Markowiak P, li ewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients. MDPI; 2017;9:1021.

Sadeghirashed S, Kazemi F, Taheri S, Ebrahimi MT, Arasteh J. A novel probiotic strain exerts therapeutic effects on mouse model of multiple sclerosis by altering the expression of inflammasome and IDO genes and modulation of T helper cytokine profile. Metab Brain Dis Springer. 2022;37:197–207.

Article  CAS  Google Scholar 

Zali A, Hajyani S, Salari M, Tajabadi-Ebrahimi M, Mortazavian AM, Pakpour B. Co-administration of probiotics and vitamin D reduced disease severity and complications in patients with Parkinson's disease: a randomized controlled clinical trial. Psychopharmacology (Berl). Springer; 2024;241:1905–14.

Laterza L, Cremon C, Coppola G, Settanni CR, Maresca R, Strazzeri M, et al. Multistrain Probiotics Plus Vitamin D Improve Gut Barrier Function and Gut Microbiota Composition in Irritable Bowel Syndrome Without Constipation: Results from a Double-Blind, Randomized, Placebo-Controlled Trial. Nutrients. MDPI; 2025;17:1708.

Tirani SA, Saneei P, Khorvash F, Askari G. Effects of probiotic and vitamin D co-supplementation on migraine index, quality of life, and oxidative stress in adults with migraine headache: a randomized triple-blinded clinical trial. Eur J Nutr Springer. 2025;64:1–12.

Google Scholar 

Aburashed R, Eghzawi A, Long D, Pace R, Madha A, Cote J. Neurofilament Light Chain and Multiple Sclerosis: Building a Neurofoundational Model of Biomarkers and Diagnosis. Neurol Int. MDPI; 2025;17:56.

Cutter G, Rudick RA, de Moor C, Singh CM, Fisher E, Koster T, et al. Serum neurofilament light-chain levels and long-term treatment outcomes in relapsing-remitting multiple sclerosis patients: A post hoc analysis of the randomized CombiRx trial. Mult Scler Journal Experimental, Transl Clin. SAGE Publications Sage UK: London, England; 2023;9:20552173231169464.

Fyfe I. Neurofilament makes light of MS treatment monitoring. Nat Rev Neurol. Nature Publishing Group UK London; 2019;15:188.

Reinert MC, Benkert P, Wuerfel J, Michalak Z, Ruberte E, Barro C, Huppke P, Stark W, Kropshofer H, Tomic D, Leppert D, Kuhle J, Brück W, Gärtner J. Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e749. https://doi.org/10.1212/NXI.0000000000000749.

Article  PubMed  PubMed Central  Google Scholar 

Zhang J-M, An J. Cytokines, inflammation and pain. Int Anesthesiol Clin. 2007;45:27.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kuwabara T, Ishikawa F, Kondo M, Kakiuchi T. The Role of IL-17 and Related Cytokines in Inflammatory Autoimmune Diseases. Mediators Inflamm. 2017;2017:3908061. https://doi.org/10.1155/2017/3908061.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fu J, Huang Y, Bao T, Liu C, Liu X, Chen X. The role of Th17 cells/IL-17A in AD, PD, ALS and the strategic therapy targeting on IL-17A. J Neuroinflammation. 2022;19(1):98. https://doi.org/10.1186/s12974-022-02446-6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gandhi R, Laroni A, Weiner HL. Role of the innate immune system in the pathogenesis of multiple sclerosis. J Neuroimmunol Elsevier. 2010;221:7–14.

Article  CAS  Google Scholar 

Chakamian K, Robat-Jazi B, Naser Moghadasi A, Mansouri F, Nodehi M, Motevaseli E, Izad M, Yekaninejad S, Shirzad M, Bidad K, Oraei M, Ansaripour B, Saboor-Yaraghi AA. Immunosuppressive Effects of Two Probiotics, Lactobacillus paracasei DSM 13434 and Lactobacillus plantarum DSM 15312, on CD4+ T Cells of Multiple Sclerosis Patients. Iran J Allergy Asthma Immunol. 2023;22(1):34–45. https://doi.org/10.18502/ijaai.v22i1.12004.

Article  PubMed  Google Scholar 

Rahimlou M, Nematollahi S, Husain D, Banaei-Jahromi N, Majdinasab N, Hosseini SA. Probiotic supplementation and systemic inflammation in relapsing-remitting multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Front Neurosci. Frontiers; 2022;16:901846.

Tamtaji OR, Kouchaki E, Salami M, Aghadavod E, Akbari E, Tajabadi-Ebrahimi M, et al. The effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled trial. J Am Coll Nutr. Taylor & Francis; 2017;36:660–5.

Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol. 2012;32(1):23–63. https://doi.org/10.1615/critrevimmunol.v32.i1.30.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gadani SP, Cronk JC, Norris GT, Kipnis J. IL-4 in the brain: a cytokine to remember. J Immunol. 2012;189:4213–9.

Article  CAS  PubMed  Google Scholar 

Chatterjee P, Chiasson VL, Bounds KR, Mitchell BM. Regulation of the anti-inflammatory cytokines interleukin-4 and interleukin-10 during pregnancy. Front Immunol. Frontiers Media SA; 2014;5:253.

Urcelay E, Santiago JL, Mas A, Martinez A, de Las HV, Arroyo R, et al. Role of interleukin 4 in Spanish multiple sclerosis patients. J Neuroimmunol Elsevier. 2005;168:164–7.

Article  CAS  Google Scholar 

Kallaur AP, Oliveira SR, Delicato de Almeida ER, Kaminami Morimoto H, Lopes J, de Carvalho Jennings Pereira WL, et al. Cytokine profile in relapsing-remitting multiple sclerosis patients and the association between progression and activity of the disease. Mol Med Rep. Spandidos Publications; 2013;7:1010–20.

Arababadi MK, Mosavi R, Ravari A, Teimori H, Hassanshahi G, King Faisal Specialist Hospital & Research Centre. Association of interleukin-4 polymorphisms with multiple sclerosis in southeastern Iranian patients. Ann Saudi Med. 2012;32:127–30.

Article  PubMed  PubMed Central  Google Scholar 

Fenn AM, Hall JCE, Gensel JC, Popovich PG, Godbout JP. IL-4 signaling drives a unique arginase+/IL-1 + microglia phenotype and recruits macrophages to the inflammatory CNS: consequences of age-related deficits in IL-4R after traumatic spinal cord injury. J Neurosci Soc Neuroscience. 2014;34:8904–17.

Article  CAS  Google Scholar 

Batlle E, Massagué J. Transforming growth factor- signaling in immunity and cancer. Immunity Elsevier. 2019;50:924–40.

Article  CAS  Google Scholar 

Lee PW, Severin ME, Lovett-Racke AE. TGF-β regulation of encephalitogenic and regulatory T cells in multiple sclerosis. Eur J Immunol. 2017;47:446–53.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sanjabi S, Oh SA, Li MO. Regulation of the immune response by TGF- : from conception to autoimmunity and infection. Cold Spring Harb Perspect Biol. Cold Spring Harbor Lab; 2017;9:a022236.

Guevara C, Ortiz FC. Glial-derived transforming growth factor 1 (TGF- 1): A key factor in multiple sclerosis neuroinflammation. Neural Regen Res. Wolters Kluwer--Medknow Publications; 2021;16:510.

Zhang S. The role of transforming growth factor in T helper 17 differentiation. Immunology Wiley Online Library. 2018;155:24–35.

CAS  Google Scholar 

Li S, Gu X, Yi S. The regulatory effects of transforming growth factor- on nerve regeneration. Cell Transplant. SAGE Publications Sage CA: Los Angeles, CA; 2017;26:381–94.

Haribhai D, Ziegelbauer J, Williams C. P-184 Alternatively Activated Macrophages Boost iTreg and Th17 Cell Responses During Immunotherapy for Colitis. Inflamm Bowel Dis Oxford University Press. 2016;22:S65–S65.

Article  Google Scholar 

Torres T, Mendes-Bastos P, Cruz MJ, Duarte B, Filipe P, Lopes MJP, Gonçalo M. Interleukin-4 and Atopic Dermatitis: Why Does it Matter? A Narrative Review. Dermatol Ther (Heidelb). 2025;15(3):579–97. https://doi.org/10.1007/s13555-025-01352-y.

Article  PubMed  Google Scholar 

Al-Qahtani AA, Alhamlan FS, Al-Qahtani AA. Pro-inflammatory and anti-inflammatory interleukins in infectious diseases: A comprehensive review. Trop Med Infect Dis. MDPI; 2024;9:13.

Pan K, Li Q, Guo Z, Li Z. Healing action of Interleukin-4 (IL-4) in acute and chronic inflammatory conditions: Mechanisms and therapeutic strategies. Pharmacol Ther. 2025;265:108760. https://doi.org/10.1016/j.pharmthera.2024.108760.

Article 

Comments (0)

No login
gif