The dual role of short fatty acid chains in the pathogenesis of autoimmune disease models
Open accessAbstract
Autoimmune diseases are influenced by both genetic and environmental factors. The gut environment has attracted much attention as an essential component that modulates immune responses, and therefore immune-mediated disorders, such as autoimmune diseases. Growing evidence suggests that microbiota and their metabolites are critical factors for immune modulation. Recently, we reported that the microbiome in patients with multiple sclerosis, an autoimmune disease targeting the myelin sheath of the central nervous system, is characterized by a reduction of bacteria belonging to Clostridia clusters IV and XIVa, which are potent producers of short-chain fatty acids (SCFAs) by fermentation of indigestible carbohydrates. In the present study, we investigated the role of SCFAs in the regulation of inflammation. We demonstrated that oral administration of SCFAs ameliorated the disease severity of systemic autoimmune inflammatory conditions mediated by lymphocytes such as experimental autoimmune encephalitis and collagen-induced arthritis. Amelioration of disease was associated with a reduction of Th1 cells and an increase in regulatory T cells. In contrast, SCFAs contributed to the exaggeration of K/BxN serum transfer arthritis, representing the effector phase of inflammation in rheumatoid arthritis. An increased understanding of the effect of microbiota metabolites will lead to the effective treatment and prevention of systemic inflammatory disorders.
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Oral administration of SCFAs ameliorated the disease severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
“In fact, it is noteworthy that oral administration of SCFAs ameliorated the disease severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS (87, 178).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [178]
Oral administration of short-chain fatty acids ameliorates experimental autoimmune encephalomyelitis development and disease severity.
“Such as, oral administration of SCFAs ameliorate EAE development and disease severity (155, 156).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [156]
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Cites
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549 · see citing works
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413 · see citing works
Role of the microbiota in immunity and inflammation.
Belkaid, Y., & Hand, T. W. (2014) · Cell · doi:10.1016/j.cell.2014.03.011 · Cited by 5,385 · see citing works
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., et al. (2013) · Nature · doi:10.1038/nature12726 · Cited by 4,838 · see citing works
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554 · see citing works
Induction of Colonic Regulatory T Cells by Indigenous <i>Clostridium</i> Species
Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. (2011) · Science · doi:10.1126/science.1198469 · Cited by 3,752 · see citing works
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., et al. (2013) · Nature · doi:10.1038/nature12331 · Cited by 2,872 · see citing works
Gut Microbiota Metabolism of Dietary Fiber Influences Allergic Airway Disease and Hematopoiesis
Trompette, A., Gollwitzer, E. S., Yadava, K., Sichelstiel, A. K., Sprenger, N., Ngom-Bru, C., Blanchard, C., Junt, T., Nicod, L. P., Harris, N. L., et al. (2014) · Nature Medicine · doi:10.1038/nm.3444 · Cited by 2,862 · see citing works
Gaboriau-Routhiau, V., Rakotobe, S., Lécuyer, E., Mulder, I., Lan, A., Bridonneau, C., Rochet, V., Pisi, A., De Paepe, M., Brandi, G., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.020 · Cited by 1,452 · see citing works
Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis
Lee, Y. K., Menezes, J. S., Umesaki, Y., & Mazmanian, S. K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000082107 · Cited by 1,323 · see citing works
Low counts of Faecalibacterium prausnitzii in colitis microbiota
Sokol, H., Seksik, P., Furet, J. P., Firmesse, O., Nion-Larmurier, I., Beaugerie, L., Cosnes, J., Corthier, G., Marteau, P., & Doré, J. (2009) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20903 · Cited by 1,275 · see citing works
Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination
Berer, K., Mues, M., Koutrolos, M., Rasbi, Z. A., Boziki, M., Johner, C., Wekerle, H., & Krishnamoorthy, G. (2011) · Nature · doi:10.1038/nature10554 · Cited by 1,251 · see citing works
Organ-specific disease provoked by systemic autoimmunity.
Kouskoff, V., Korganow, A., Duchatelle, V., Degott, C., Benoist, C., & Mathis, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81989-3 · Cited by 949 · see citing works
Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine
Haghikia, A., Jörg, S., Duscha, A., Berg, J., Manzel, A., Waschbisch, A., Hammer, A., Lee, D.-H., May, C., Wilck, N., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.09.007 · Cited by 927 · see citing works
Miyake, S., Kim, S., Suda, W., Oshima, K., Nakamura, M., Matsuoka, T., Chihara, N., Tomita, A., Sato, W., Kim, S.-W., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137429 · Cited by 809 · see citing works
Mast Cells: A Cellular Link Between Autoantibodies and Inflammatory Arthritis
Lee, D. M., Friend, D. S., Gurish, M. F., Benoist, C. O., Mathis, D. J., & Brenner, M. B. (2002) · Science · doi:10.1126/science.1073176 · Cited by 751 · see citing works
From Systemic T Cell Self-Reactivity to Organ-Specific Autoimmune Disease via Immunoglobulins
Korganow, A., Ji, H., Mangialaio, S., Duchatelle, V., Pelanda, R., Martin, T., Degott, C., Kikutani, H., Rajewsky, K., Pasquali, J., et al. (1999) · Immunity · doi:10.1016/s1074-7613(00)80045-x · Cited by 691 · see citing works
Arthritis Critically Dependent on Innate Immune System Players
Ji, H., Ohmura, K., Mahmood, U., Lee, D. M., Hofhuis, F. M., Boackle, S. A., Takahashi, K., Holers, V. M., Walport, M. J., Gerard, C. J., et al. (2002) · Immunity · doi:10.1016/s1074-7613(02)00275-3 · Cited by 687 · see citing works
Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme.
Matsumoto, I., Staub, A., Benoist, C., & Mathis, D. (1999) · Science · doi:10.1126/science.286.5445.1732 · Cited by 667 · see citing works
Wipke, B. T., & Allen, P. M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.3.1601 · Cited by 588 · see citing works
Periodontal disease and the oral microbiota in new‐onset rheumatoid arthritis
Scher, J. U., Úbeda, C., Equinda, M. J., Khanin, R., Buischi, Y. D. P., Viale, A. J., Lipuma, L., Attur, M. G., Pillinger, M. H., Weissmann, G., et al. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34539 · Cited by 465 · see citing works
Lebrero‐Fernández, C., Bergström, J. H., Pelaseyed, T., & Bas‐Forsberg, A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00001 · Cited by 371 · see citing works
Ochoa-Repáraz, J., Mielcarz, D. W., Ditrio, L. E., Burroughs, A. R., Begum-Haque, S., Dasgupta, S., Kasper, D. L., & Kasper, L. H. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001443 · Cited by 367 · see citing works
Critical Roles for Interleukin 1 and Tumor Necrosis Factor α in Antibody-induced Arthritis
Ji, H., Pettit, A. R., Ohmura, K., Ortiz-Lopez, A., Duchatelle, V., Degott, C., Gravallese, E. M., Mathis, D. J., & Benoist, C. O. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020439 · Cited by 329 · see citing works
NKT Cell-Dependent Amelioration of a Mouse Model of Multiple Sclerosis by Altering Gut Flora
Yokote, H., Miyake, S., Croxford, J. L., Oki, S., Mizusawa, H., & Yamamura, T. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080622 · Cited by 264 · see citing works
Self-citationDual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy
Bhattacharya, P., Budnick, I., Singh, M., Thiruppathi, M., Alharshawi, K., Elshabrawy, H. A., Holterman, M., & Prabhakar, B. S. (2015) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2014.0149 · Cited by 264 · see citing works
Fuggle, N. R., Smith, T. O., Kaul, A., & Sofat, N. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00080 · Cited by 234 · see citing works
Rahman, M. M., Kukita, A., Kukita, T., Shobuike, T., Nakamura, T., & Kohashi, O. (2003) · Blood · doi:10.1182/blood-2002-08-2622 · Cited by 217 · see citing works
GM-CSF: An immune modulatory cytokine that can suppress autoimmunity
Bhattacharya, P., Thiruppathi, M., Elshabrawy, H. A., Alharshawi, K., Kumar, P., & Prabhakar, B. S. (2015) · Cytokine · doi:10.1016/j.cyto.2015.05.030 · Cited by 208 · see citing works
Lefrançois, L., & Lycke, N. Y. (1996) · Current Protocols in Immunology · doi:10.1002/0471142735.im0319s17 · Cited by 207 · see citing works
Biphasic effect of interferon‐γ in murine collagen‐induced arthritis
Boissier, M., Chiocchia, G., Bessis, N., et al. (1995) · European Journal of Immunology · doi:10.1002/eji.1830250508 · Cited by 204 · see citing works
Gurav, A., Sivaprakasam, S., Bhutia, Y. D., Boettger, T., Singh, N., & Ganapathy, V. (2015) · Biochemical Journal · doi:10.1042/bj20150242 · Cited by 166 · see citing works
Park, J., Goergen, C. J., HogenEsch, H., & Kim, C. H. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502046 · Cited by 166 · see citing works
A crucial role for macrophages in the pathology of K/B × N serum‐induced arthritis
Solomon, S., Rajasekaran, N., Jeisy‐Walder, E., Snapper, S. B., & Illges, H. (2005) · European Journal of Immunology · doi:10.1002/eji.200526167 · Cited by 135 · see citing works
Ang, Z., Er, J. Z., Tan, N. S., Lu, J., Liou, Y., Grosse, J., & Ding, J. L. (2016) · Scientific Reports · doi:10.1038/srep34145 · Cited by 100 · see citing works
Chang, M. ‐., Tsai, Y., Chen, Y., Chan, C.-C., Huang, C.-X., Lan, W. C., Lin, C., Lan, W. H., & Jeng, J. (2012) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2012.01504.x · Cited by 93 · see citing works
Wang, F., Liu, J., Weng, T., Shen, K., Chen, Z., Yu, Y., Huang, Q., Wang, G., Liu, Z., & Jin, S. (2016) · Scandinavian Journal of Immunology · doi:10.1111/sji.12515 · Cited by 79 · see citing works
Granulocyte–Macrophage Colony-Stimulating Factor Autoantibodies
Gathungu, G. N., Kim, M., Ferguson, J. P., Sharma, Y., Zhang, W., Ng, S. M. E., Bonkowski, E. L., Ning, K., Simms, L. A., Croft, A. R., et al. (2013) · Inflammatory Bowel Diseases · doi:10.1097/mib.0b013e318281f506 · Cited by 73 · see citing works
Cook, A. D., Turner, A. L., Braine, E. L., Pobjoy, J., Lenzo, J. C., & Hamilton, J. A. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30354 · Cited by 73 · see citing works
Living with Cat and Dog Increases Vaginal Colonization with E. coli in Pregnant Women
Stokholm, J., Schjørring, S., Pedersen, L., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046226 · Cited by 71 · see citing works
Rowin, J., Thiruppathi, M., Arhebamen, E., Sheng, J., Prabhakar, B. S., & Meriggioli, M. N. (2012) · Muscle & Nerve · doi:10.1002/mus.23488 · Cited by 64 · see citing works
Farooq, S. M., & Ashour, H. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048635 · Cited by 39 · see citing works
Eye‐mediated immune tolerance to Type II collagen in arthritis‐prone strains of mice
Farooq, S. M., Kumar, A., & Ashour, H. M. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12376 · Cited by 33 · see citing works
Kaieda, S., Tomi, C., Oki, S., Yamamura, T., & Miyake, S. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22714 · Cited by 32 · see citing works
Self-citationEye‐Mediated Induction of Specific Immune Tolerance to Encephalitogenic Antigens
Farooq, S. M., & Ashour, H. M. (2013) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12087 · Cited by 27 · see citing works
Age-dependent divergent effects of OX40L treatment on the development of diabetes in NOD mice
Haddad, C., Bhattacharya, P., Alharshawi, K., Marinelarena, A. M., Kumar, P., El-Sayed, O. M., Elshabrawy, H. A., Epstein, A. L., & Prabhakar, B. S. (2016) · Autoimmunity · doi:10.1080/08916934.2016.1183657 · Cited by 25 · see citing works
Farooq, S. M., Elkhatib, W. F., & Ashour, H. M. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.06.010 · Cited by 23 · see citing works
In vitro-induced cell-mediated immune deviation to encephalitogenic antigens.
Farooq, S., & Ashour, H. (2014) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2013.09.016 · Cited by 18 · see citing works
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The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
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“In fact, it is noteworthy that oral administration of SCFAs ameliorated the disease severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS (87, 178).”
BackgroundShort-chain fatty acids: Linking diet, the microbiome and immunity
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Chen, T., Noto, D., Hoshino, Y., Mizuno, M., & Miyake, S. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1552-y · Cited by 229 · see citing works
Self-citationChidambaram, S. B., Essa, M. M., Rathipriya, A. G., Bishir, M., Ray, B., Mahalakshmi, A. M., Tousif, A. H., Sakharkar, M. K., Kashyap, R. S., Friedland, R. P., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107988 · Cited by 204 · see citing works
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Jiang, J., Chu, C., Wu, C., Wang, C., Zhang, C., Li, T., Zhai, Q., Yu, L., Tian, F., & Chen, W. (2021) · Food & Function · doi:10.1039/d0fo03203d · Cited by 52 · see citing works
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- Authors
- Mizuno, M., Noto, D., Kaga, N., Chiba, A., & Miyake, S.
- Affiliations
- Juntendo University (JP)
- Corresponding author
- Mizuno, Miho
- Noto, Daisuke
- Kaga, Naoko
- Chiba, Asako
- Miyake, Sachiko
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-02-24
- Volume
- 12
- Issue
- 2
- Pages
- e0173032
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5325617
- OpenAlex
- W2589854016
- Cited by
- 230
- References
- 48
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 24 · 2023: 23 · 2022: 39 · 2021: 31 · 2020: 29 · 2019: 15 · 2018: 22 · 2017: 9
- FWCI
- 8.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Grant-in Aid for Scientific Research from the Japan Society for the Promotion of Science (B: 26293234)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- short-chain fatty acids, gut microbiota, microbiota metabolites, autoimmune disease, experimental autoimmune encephalitis, collagen-induced arthritis, K/BxN serum transfer arthritis, rheumatoid arthritis, multiple sclerosis, Th1 cells, regulatory T cells, inflammation, Clostridia, dietary intervention
- MeSH terms
- Administration, Oral, Animals, Anti-Inflammatory Agents, Arthritis, Experimental, Drug Evaluation, Preclinical, Encephalomyelitis, Autoimmune, Experimental, Fatty Acids, Volatile, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Th1 Cells, T-Lymphocytes, Regulatory
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