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Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response
Abstract
The immunomodulatory effect of probiotics has been shown mainly in gastro-intestinal immune disorders and little information is available on the inflammation of central nervous system. Recently we reported that IRT5 probiotics, a mixture of 5 probiotics, could suppress diverse experimental inflammatory disorders. In this study, we evaluated the prophylactic and therapeutic effects of IRT5 probiotics in experimental autoimmune encephalomyelitis (EAE), a T cell mediated inflammatory autoimmune disease of the central nervous system. Pretreatment of IRT5 probiotics before disease induction significantly suppressed EAE development. In addition, treatment with IRT5 probiotics to the ongoing EAE delayed the disease onset. Administration of IRT5 probiotics inhibited the pro-inflammatory Th1/Th17 polarization, while inducing IL10(+) producing or/and Foxp3(+) regulatory T cells, both in the peripheral immune system and at the site of inflammation. Collectively, our data suggest that IRT5 probiotics could be applicable to modulate T cell mediated neuronal autoimmune diseases, including multiple sclerosis.
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“Animal studies suggest that probiotics can modulate endogenous neuroactive molecules [17], prevent and treat neuronal autoimmune diseases [18], and ameliorate impaired spatial memory in diabetic rats [19].”
From Effect of Supplementation with Probiotics in Patients with Schizophrenia: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials (2025) · cites this paper as [18]
In the citing paper
“The supplementation of a cocktail of five probiotics (IRT5) before or after the EAE onset in rodents is associated with the delay of the disease onset or suppression of the disease progression, respectively (154).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [154]
In the citing paper
“The amelioration of the disease upon probiotic treatment was associated with a higher abundance of Treg cells, higher production of IL-10 by CD4+ T cells, B cells, and CD11c+ cells, together with the suppression of the pro-inflammatory Th-1/Th-17 response (154).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [154]
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“Then, DCs were co-cultured with “circulating” antigen- specific CD4 Teff cells (Figure 6A) and since it has been suggested that probiotics can induce immune tolerance either/or promoting Treg activity and/or suppressing T helper response (5), we wondered whether bifidobacteria treatment could influence Tcell motility,…”
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“A wide variety of research has identified that IRT5 could alleviate various preclinical models of immune diseases, including IBD, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, and skin allergy, suggesting its promising therapeutic potential in clinical fields (98-100).”
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“Interestingly, supplementation of probiotics to the EAE mice model enhances their therapeutic grade by increasing the production of IL-10-producing Tregs [147].”
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“The probable mechanism of probiotics treatment’s effects may comprise the elimination of pathogenic microorganisms and immune system modulation (Kwon et al., 2013).”
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“We used data of 19 independent groups for this analysis that were extracted from 12 studies (Baken et al. 2006; Ezendam et al. 2008; Ezendam and van Loveren 2008; Takata et al. 2011; Kobayashi et al. 2012; Kwon et al. 2013; Abdurasulova et al. 2016b; Abdurasulova et al. 2017; Salehipour et al. 2017; Secher et al. 2017…”
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“Another scientist, Kwon et al., showed that while using a mixture of certain probiotics could improve experimental autoimmune encephalo-myelitis (EAE), a combination of other probiotics could not alleviate the clinical symptoms of EAE [146].”
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Dolan, K. E., Finley, H. J., Burns, C. M., Gasta, M. G., Gossard, C. M., Parker, E., Pizano, J. M., Williamson, C. B., & Lipski, E. A. (2016) · PubMed Central · Cited by 13
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“Compared with other studies, these results suggest that oral administration of a probiotics mixture effectively prevents or treats EAE (Kwon et al., 2013; Lavasani et al., 2010).”
BackgroundResultInfluentialBanerjee, A., Pradhan, L. K., Sahoo, P. K., Jena, K. K., Chauhan, N. R., Chauhan, S., & Das, S. K. (2021) · Archives of Microbiology · doi:10.1007/s00203-021-02276-9 · Cited by 13
The Role of Probiotics In Tissue Engineering And Regenerative Medicine
Golchin, A., Ranjbarvan, P., Parviz, S., Shokati, A., Naderi, R., Rasmi, Y., Kiani, S., Moradi, F., Heidari, F., Saltanatpour, Z., et al. (2023) · Regenerative Medicine · doi:10.2217/rme-2022-0209 · Cited by 12
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“The composition of SCFAs was estimated from the cecal content using the previously described methods [68].”
MethodMicrobiome Methods in Experimental Autoimmune Encephalomyelitis
Daberkow, D. P., Hoffman, K. R., Kohl, H. M., Long, T., Kirby, T. O., & Ochoa‐Repáraz, J. (2021) · Current Protocols · doi:10.1002/cpz1.314 · Cited by 10
“…Cekanaviciute et al., 2017), monocolonization studies (Berer et al., 2011; Lee et al., 2011), probiotic approaches (Calvo-Barreiro et al., 2020; Kwon et al., 2013; Lavasani et al., 2010; Maassen & Claassen, 2008; Mangalam et al., 2017; Secher et al., 2017; Shahi et al., 2019; Tankou et al.,…”
BackgroundThe Gut-Brain Axis in Autoimmune Diseases: Emerging Insights and Therapeutic Implications
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“Studies have shown that the use of mono- and multicomponent probiotics based on lactobacilli can reduce the severity of EAE in mice [36, 38, 41, 63].”
BackgroundBifidobacteria: A probable missing puzzle piece in the pathogenesis of multiple sclerosis
Toghi, M., Bitarafan, S., Kasmaei, H. D., & Ghafouri‐Fard, S. (2019) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2019.101378 · Cited by 11
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“Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus reuteni, Bifidobacterium bifidum and Streptococcus thermiphilus which slows down the proinflammatory Th1/Th17 polarization.(77) Lactobacillus Plantarum and Bifidobacterium B94 combined treatment promote spatial memory in MS.”
BackgroundOral Lactobacillus Species in Systemic Sclerosis
Melchiorre, D., Ceccherini, M. T., Romano, E., Cometi, L., Aoufy, K. E., Bellando-Randone, S., Roccotelli, A., Bruni, C., Pignone, A. M., Carboni, D., et al. (2021) · Microorganisms · doi:10.3390/microorganisms9061298 · Cited by 8
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BackgroundMethodProbiotic supplementation has little effect on peripheral blood regulatory T cells
West, N. P., Horn, P. L., Pyne, D. B., Warren, H. S., Asad, S., Cox, A. J., Lahtinen, S. J., Lehtinen, M. J., Fricker, P. A., Cripps, A. W., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.06.055 · Cited by 8
“growing body of evidence indicates that probiotic b a teria are able to induce T-regs in various animal odels of 18 inflammation, including food allergy, experimental autoimmune encephalomyelitis, colitis and rotavirus 19 vaccination [4-7].”
BackgroundProbiotic Applications in Autoimmune Diseases
de Oliveira, G. L. V. (2018) · InTech eBooks · doi:10.5772/intechopen.73064 · Cited by 8
“These actions were due probably by induction of CD4+Foxp3+ Treg cells and IL-10 secretion at sites of inflammation and peripheral lymph nodes [46].”
BackgroundThe Role of Gut-derived Short-Chain Fatty Acids in Multiple Sclerosis
Saadh, M. J., Ahmed, H. M., Alani, Z. K., Zuhairi, R. A. H. A., Almarhoon, Z. M., Ahmad, H., Ubaid, M., & Alwan, N. H. (2024) · NeuroMolecular Medicine · doi:10.1007/s12017-024-08783-4 · Cited by 8
“In order to slow the progression of EAE and possibly MS, these findings suggest that IRT5 probiotics could be utilized as a preventative measure or dietary supplement (Kwon et al., 2013).”
El holobionte enfermo, el ejemplo de la esclerosis múltiple
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“Animal studies suggest that probiotics can modulate endogenous neuroactive molecules [17], prevent and treat neuronal autoimmune diseases [18], and ameliorate impaired spatial memory in diabetic rats [19].”
Lymphocytes T Helper 17 in Multiple Sclerosis: Regulation by Intestinal Microbiota
Moreira, B. B. D. S., Franzoi, A. E. D. A., Gonçalves, M. V. M., Nascimento, O. J. M., & Peron, J. P. S. (2019) · Journal of Neurology and Experimental Neuroscience · doi:10.17756/jnen.2019-051 · Cited by 7
“reuteni, Bifidobacterium bifidum, and Streptococcus thermophilus - known as IRT5, also ameliorated EAE prophylactically and therapeutically decreased Th1 and Th17 but increased IL-4 and IL-10 from CD4+ T cells [42].”
BackgroundAbbasi, S., Akhavan-Sigari, A., Rostami, S., Sedaghat, N., & Tavakoli, R. (2023) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2023.02.025 · Cited by 6
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Gut microbiota and autoimmune diseases: Insights from Mendelian randomization
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“32,33 Furthermore, these beneficial microbes bol-ster the integrity of intestinal mucosal barrier, protecting bloodstream from harmful agents, and pathogens infiltration.”
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Gut Microbiome as Potential Therapeutics in Multiple Sclerosis
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Can the Therapeutic Spectrum of Probiotics be Extended: Exploring Potential of Gut Microbiome
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“Trials in EAE in which probiotics were used have shown ef - ficacy [132].”
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Microbiota and Neurodegenerative Diseases
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“Regulatory processes of the Th1/Th2 response mainly involve induction of T regulator (Treg) Foxp3+ cells (Kwon et al., 2013; Lavasani et al., 2010; Ogawa et al., 2016; Tankou et al., 2018).”
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Gut Microbiome Influences The Neuroinflammatory Response To Traumatic Brain InjuryPreprint
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Metadata
- Authors
- Kwon, H.-K., Kim, G.-C., Kim, Y., Hwang, W., Jash, A., Sahoo, A., Kim, J.-E., Nam, J. H., & Im, S.-H.
- Affiliations
- Harvard University (US)
- Gwangju Institute of Science and Technology (KR)
- Chonnam National University (KR)
- Washington University in St. Louis (US)
- Corresponding author
- Im, Sin-Hyeog
- ORCID
- Venue
- Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 146
- Issue
- 3
- Pages
- 217-227
- ISSN
- 1521-6616 (ISSN-L)
- OpenAlex
- W2078792455
- Cited by
- 212
- References
- 48
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 11 · 2023: 29 · 2022: 20 · 2021: 27 · 2020: 19 · 2019: 20 · 2018: 23 · 2017: 24 · 2016: 12 · 2015: 11 · 2014: 2 · 2013: 2
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation (2011-0028529)
- Systems Biology Infrastructure Establishment Grant
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- experimental autoimmune encephalomyelitis, probiotics, T helper cell polarization, Th1/Th17 cells, regulatory T cells, Foxp3, IL-10, immunomodulation, multiple sclerosis, neuroinflammation, T cell-mediated autoimmunity
- MeSH terms
- Animals, Encephalomyelitis, Autoimmune, Experimental, T-Lymphocytes, Helper-Inducer, Mice, Inbred C57BL, Peptide Fragments, Spinal Cord, T-Lymphocyte Subsets, Probiotics, Mice, Myelin-Oligodendrocyte Glycoprotein
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