Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine
Open accessAbstract
Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis.
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A metagenome-wide association study of gut microbiota in type 2 diabetes
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012) · Nature · doi:10.1038/nature11450 · Cited by 6,762 · see citing works
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
Diversity, stability and resilience of the human gut microbiota
Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight, R. (2012) · Nature · doi:10.1038/nature11550 · Cited by 5,533 · 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
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
The impact of the gut microbiota on human health: an integrative view
Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012) · Cell · doi:10.1016/j.cell.2012.01.035 · Cited by 3,710 · see citing works
Short chain fatty acids in human large intestine, portal, hepatic and venous blood
Cummings, J. H., Pomare, E. W., Branch, W. J., Naylor, C. P., & Macfarlane, G. T. (1987) · Gut · doi:10.1136/gut.28.10.1221 · Cited by 3,119 · 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
Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P. D., Manicassamy, S., Munn, D. H., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.12.007 · Cited by 2,368 · see citing works
Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis
Viglietta, V., Baecher‐Allan, C., Weiner, H. L., & Hafler, D. A. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031579 · Cited by 1,858 · see citing works
Dietary intervention impact on gut microbial gene richness
Cotillard, A., Kennedy, S. P., Kong, L. C., Prifti, E., Pons, N., Le Chatelier, E., Almeida, M., Quinquis, B., Levenez, F., Galleron, N., et al. (2013) · Nature · doi:10.1038/nature12480 · Cited by 1,832 · see citing works
Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells
Kleinewietfeld, M., Manzel, A., Titze, J., Kvakan, H., Yosef, N., Linker, R. A., Muller, D. N., & Hafler, D. A. (2013) · Nature · doi:10.1038/nature11868 · Cited by 1,394 · see citing works
Self-citationCommensal 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
Kim, M. H., Kang, S. G., Park, J. H., Yanagisawa, M., & Kim, C. H. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.04.056 · Cited by 1,127 · see citing works
Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1
Wu, C., Yosef, N., Thalhamer, T., Zhu, C., Xiao, S., Kishi, Y., Regev, A., & Kuchroo, V. K. (2013) · Nature · doi:10.1038/nature11984 · Cited by 1,022 · see citing works
Control of TH17 cells occurs in the small intestine
Esplugues, E., Huber, S., Gagliani, N., Hauser, A. E., Town, T., Wan, Y. Y., O’Connor, W., Rongvaux, A., van Rooijen, N., Haberman, A. M., et al. (2011) · Nature · doi:10.1038/nature10228 · Cited by 653 · see citing works
The role of the immune system in governing host-microbe interactions in the intestine
Brown, E., Sadarangani, M., & Finlay, B. B. (2013) · Nature Immunology · doi:10.1038/ni.2611 · Cited by 403 · see citing works
CD3-specific antibodies: a portal to the treatment of autoimmunity
Chatenoud, L., & Bluestone, J. A. (2007) · Nature reviews. Immunology · doi:10.1038/nri2134 · Cited by 389 · see citing works
Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis
Hedström, A. K., Sundqvist, E., Bäärnhielm, M., Nordin, N. S., Hillert, J. A., Kockum, I. S., Olsson, T. P., & Alfredsson, L. S. (2011) · Brain · doi:10.1093/brain/awq371 · Cited by 271 · see citing works
Regulatory T cells in autoimmune neuroinflammation
Kleinewietfeld, M., & Hafler, D. A. (2014) · Immunological Reviews · doi:10.1111/imr.12169 · Cited by 230 · see citing works
Self-citationMacia, L., Thorburn, A. N., Binge, L. C., Mariño, E., Rogers, K. E., Maslowski, K. M., Vieira, A. T., Kranich, J., & Mackay, C. R. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01080.x · Cited by 223 · see citing works
Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis
Hedström, A. K., Bomfim, I. L., Barcellos, L. F., Gianfrancesco, M. A., Schaefer, C. A., Kockum, I. S., Olsson, T. P., & Alfredsson, L. S. (2014) · Neurology · doi:10.1212/wnl.0000000000000203 · Cited by 223 · see citing works
Beyersdorf, N., Gaupp, S., Balbach, K., Schmidt, J., Toyka, K. V., Lin, C.-H., Hanke, T., Hünig, T., Kerkau, T., & Gold, R. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051060 · Cited by 203 · see citing works
Self-citationThe storm has cleared: lessons from the CD28 superagonist TGN1412 trial
Hünig, T. (2012) · Nature Reviews Immunology · doi:10.1038/nri3192 · Cited by 194 · cited 2× · see citing works
“, 2005) but not practically feasible outside of controlled experimental conditions (Hünig, 2012).”
Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis
Noubade, R., Krementsov, D. N., del Río, R., Thornton, T. M., Nagaleekar, V. K., Saligrama, N., Spitzack, A., Spach, K. M., Sabio, G., Davis, R. J., et al. (2011) · Blood · doi:10.1182/blood-2011-02-336552 · Cited by 164 · see citing works
Tanaka, S., Suto, A., Iwamoto, T., Kashiwakuma, D., Kagami, S., Suzuki, K., Takatori, H., Tamachi, T., Hirose, K., Onodera, A., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20130791 · Cited by 128 · see citing works
Role and function of macrophages in the metabolic syndrome
Bhargava, P., & Lee, C. (2012) · Biochemical Journal · doi:10.1042/bj20111708 · Cited by 114 · see citing works
Ostermann, A. I., Müller, M., Willenberg, I., et al. (2014) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2014.10.002 · Cited by 112 · see citing works
Self-citationTherapies for multiple sclerosis: translational achievements and outstanding needs
Haghikia, A., Hohlfeld, R., Gold, R., & Fugger, L. H. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.03.004 · Cited by 108 · see citing works
Self-citationJNK and p38 MAP kinases in CD4+ and CD8+ T cells
Rincón, M., & Pedraza‐Alva, G. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00019.x · Cited by 104 · see citing works
Lipin-2 Reduces Proinflammatory Signaling Induced by Saturated Fatty Acids in Macrophages
Valdearcos, M., Esquinas, E., Meana, C., Peña, L., Gil‐de‐Gómez, L., Balsinde, J., & Balboa, M. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.342915 · Cited by 102 · see citing works
Krementsov, D. N., Noubade, R., Dragon, J. A., Otsu, K., Rincón, M., & Teuscher, C. (2013) · Annals of Neurology · doi:10.1002/ana.24020 · Cited by 52 · see citing works
Response to 'Storm forecasting: additional lessons from the CD28 superagonist TGN1412 trial'
Hünig, T. (2012) · Nature reviews. Immunology · doi:10.1038/nri3192-c2 · Cited by 48 · see citing works
Counter-regulation of T cell effector function by differentially activated p38
Alam, M. S., Gaida, M. M., Ogawa, Y., Kolios, A. G. A., Lasitschka, F., & Ashwell, J. D. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131917 · Cited by 40 · see citing works
Molecular Basis of T-cell DifferentiationPreprint
Flavell, R. A., Li, B., Dong, C., Lu, H., Yang, D. D., Enslen, H., Tournier, C., Whitmarsh, A. J., Wysk, M., Conze, D. B., et al. (1999) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1999.64.563 · Cited by 30 · see citing works
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Interaction between microbiota and immunity in health and disease
Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Research · doi:10.1038/s41422-020-0332-7 · Cited by 3,947 · see citing works
Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quera, R., Dijkstra, G., Harmsen, H. J. M., Faber, K. N., & Hermoso, M. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00277 · Cited by 3,820 · see citing works
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043 · see citing works
“One of the best-documented effects of SCFAs is on the immune system since butyrate is capable of inducing Treg differentiation and controlling inflammation (17, 23, 24, 87).”
BackgroundInteractions between the microbiota, immune and nervous systems in health and disease
Fung, T. C., Olson, C. A., & Hsiao, E. Y. (2017) · Nature Neuroscience · doi:10.1038/nn.4476 · Cited by 1,900 · see citing works
The microbiota in adaptive immune homeostasis and disease
Honda, K., & Littman, D. R. (2016) · Nature · doi:10.1038/nature18848 · Cited by 1,846 · see citing works
You are what you eat: Diet, health and the gut microbiota
Zmora, N., Suez, J., & Elinav, E. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0061-2 · Cited by 1,792 · see citing works
Salt-responsive gut commensal modulates TH17 axis and disease
Wilck, N., Matus, M. G., Kearney, S. M., Olesen, S. W., Forslund, K., Bartolomaeus, H., Haase, S., Mähler, A., Balogh, A., Markó, L., et al. (2017) · Nature · doi:10.1038/nature24628 · Cited by 1,310 · see citing works
Self-citationMartin, C. R., Osadchiy, V., Kalani, A., & Mayer, E. A. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.04.003 · Cited by 1,284 · see citing works
The Health Benefits of Dietary Fibre
Barber, T. M., Kabisch, S., Pfeiffer, A. F. H., & Weickert, M. O. (2020) · Nutrients · doi:10.3390/nu12103209 · Cited by 892 · see citing works
“SCFAs may also cross the blood–brain barrier and exert direct effects on hypothalamic regulation of metabolic pathways and appetite [63,64].”
BackgroundThe gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology
Rutsch, A., Kantsjö, J. B., & Ronchi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604179 · Cited by 821 · see citing works
Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss
Lucas, S., Omata, Y., Hofmann, J., Böttcher, M., Iljazovic, A., Sarter, K., Albrecht, O., Schulz, O., Krishnacoumar, B., Krönke, G., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02490-4 · Cited by 815 · see citing works
The multiple pathways to autoimmunity
Theofilopoulos, A. N., Kono, D. H., & Baccala, R. (2017) · Nature Immunology · doi:10.1038/ni.3731 · Cited by 590 · see citing works
Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota
Cignarella, F., Cantoni, C., Ghezzi, L., Salter, A., Dorsett, Y., Chen, L., Phillips, D., Weinstock, G. M., Fontana, L., Cross, A. H., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.05.006 · Cited by 568 · see citing works
The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications
Osadchiy, V., Martin, C. R., & Mayer, E. A. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.10.002 · Cited by 555 · see citing works
Luu, M., Pautz, S., Kohl, V., Singh, R., Romero, R., Lucas, S., Hofmann, J., Raifer, H., Vachharajani, N., Carrascosa, L. C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08711-2 · Cited by 508 · see citing works
Erny, D., Dokalis, N., Mezö, C., Castoldi, A., Mossad, O., Staszewski, O., Frosch, M., Villa, M., Fuchs, V., Mayer, A., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.10.010 · Cited by 478 · see citing works
Microbiota-derived metabolites as drivers of gut–brain communication
Ahmed, H., Leyrolle, Q., Koistinen, V., Kärkkäinen, O., Layé, S., Delzenne, N., & Hanhineva, K. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2102878 · Cited by 462 · see citing works
Chambers, E. S., Byrne, C. S., Morrison, D. J., Murphy, K. G., Preston, T., Tedford, C., Garcia-Perez, I., Fountana, S., Serrano-Contreras, J. I., Holmes, E., et al. (2019) · Gut · doi:10.1136/gutjnl-2019-318424 · Cited by 443 · see citing works
The progress of gut microbiome research related to brain disorders
Zhu, S., Jiang, Y., Xu, K., Cui, M., Ye, W., Zhao, G., Jin, L., & Chen, X. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1705-z · Cited by 419 · see citing works
The gut-bone axis: How bacterial metabolites bridge the distance
Zaiss, M. M., Jones, R. M., Schett, G., & Pacifici, R. (2019) · Journal of Clinical Investigation · doi:10.1172/jci128521 · Cited by 403 · see citing works
Kim, C. H. (2023) · Cellular & Molecular Immunology · doi:10.1038/s41423-023-00987-1 · Cited by 420 · see citing works
Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids
Kim, C. H. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-00625-0 · Cited by 404 · see citing works
Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition
Colombo, A. V., Sadler, R. K., Llovera, G., Singh, V., Roth, S., Heindl, S., Sebastian Monasor, L., Verhoeven, A., Peters, F., Parhizkar, S., et al. (2021) · eLife · doi:10.7554/elife.59826 · Cited by 354 · see citing works
Rau, M., Rehman, A., Dittrich, M., Groen, A. K., Hermanns, H. M., Seyfried, F., Beyersdorf, N., Dandekar, T., Rosenstiel, P., & Geier, A. (2018) · United European Gastroenterology Journal · doi:10.1177/2050640618804444 · Cited by 334 · see citing works
Connecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex
Rizzetto, L., Fava, F., Tuohy, K. M., & Selmi, C. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.05.008 · Cited by 331 · see citing works
The Influence of Dietary Fatty Acids on Immune Responses
Radzikowska, U., Rinaldi, A. O., Çelebi Sözener, Z., Karaguzel, D., Wojcik, M., Cypryk, K., Akdis, M., Akdis, C. A., & Sokolowska, M. (2019) · Nutrients · doi:10.3390/nu11122990 · Cited by 306 · see citing works
The Microbial Metabolite Butyrate Induces Expression of Th1-Associated Factors in CD4+ T Cells
Kespohl, M., Vachharajani, N., Luu, M., Harb, H., Pautz, S., Wolff, S., Sillner, N., Walker, A., Schmitt-Kopplin, P., Boettger, T., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01036 · Cited by 294 · see citing works
TH17 cell heterogeneity and its role in tissue inflammation
Schnell, A., Littman, D. R., & Kuchroo, V. K. (2023) · Nature Immunology · doi:10.1038/s41590-022-01387-9 · Cited by 286 · see citing works
Pellegrini, C., Antonioli, L., Colucci, R., Blandizzi, C., & Fornai, M. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1856-5 · Cited by 270 · see citing works
T cell responses in the central nervous system
Korn, T., & Kallies, A. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.144 · Cited by 268 · see citing works
Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity
Schnell, A., Huang, L., Singer, M., Singaraju, A., Barilla, R. M., Regan, B. M. L., Bollhagen, A., Thakore, P. I., Dionne, D., Delorey, T. M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.11.018 · Cited by 268 · see citing works
Graves, J. S., Krysko, K. M., Hua, L. H., Absinta, M., Franklin, R. J. M., & Segal, B. M. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00184-3 · Cited by 260 · see citing works
Impacts of microbiome metabolites on immune regulation and autoimmunity
Haase, S., Haghikia, A., Wilck, N., Müller, D. N., & Linker, R. A. (2018) · Immunology · doi:10.1111/imm.12933 · Cited by 239 · see citing works
Chen, L., Sun, M., Wu, W., Yang, W., Huang, X., Xiao, Y., Ma, C., Xu, L., Yao, S., Liu, Z., et al. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izz046 · Cited by 231 · see citing works
Butyrate suppresses demyelination and enhances remyelination
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
The dual role of short fatty acid chains in the pathogenesis of autoimmune disease models
Mizuno, M., Noto, D., Kaga, N., Chiba, A., & Miyake, S. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173032 · Cited by 230 · see citing works
The function of gut microbiota in immune-related neurological disorders: a review
Sittipo, P., Choi, J., Lee, S., & Lee, Y. K. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02510-1 · Cited by 221 · see citing works
Gut microbiota, diet, and obesity-related disorders: the good, the bad, and the future challenges
Portune, K. J., Benítez‐Páez, A., Del Pulgar, E. M. G., Cerrudo, V., & Sanz, Y. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600252 · Cited by 201 · see citing works
Chidambaram, 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
The role of the gut microbiota in multiple sclerosis
Correale, J., Hohlfeld, R., & Baranzini, S. E. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00697-8 · Cited by 207 · see citing works
Takahashi, D., Hoshina, N., Kabumoto, Y., Maeda, Y., Suzuki, A., Tanabe, H., Isobe, J., Yamada, T., Muroi, K., Yanagisawa, Y., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102913 · Cited by 205 · see citing works
Deciphering the Chemical Lexicon of Host–Gut Microbiota Interactions
Nicolas, G. R., & Chang, P. V. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.04.006 · Cited by 195 · see citing works
The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis
Freedman, S. N., Shahi, S. K., & Mangalam, A. K. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0588-x · Cited by 168 · see citing works
Leonard, M. M., Valitutti, F., Karathia, H., Pujolassos, M., Kenyon, V., Fanelli, B., Troisi, J., Subramanian, P., Camhi, S., Colucci, A., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2020322118 · Cited by 162 · see citing works
Sodium in the microenvironment regulates immune responses and tissue homeostasis
Müller, D. N., Wilck, N., Haase, S., Kleinewietfeld, M., & Linker, R. A. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-018-0113-4 · Cited by 149 · see citing works
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Myers, B., Brownstone, N., Reddy, V., Chan, S., Thibodeaux, Q., Truong, A., Bhutani, T., Chang, H.-W., & Liao, W. (2019) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2020.101494 · Cited by 127 · see citing works
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Ma, H., Tao, W., & Zhu, S. (2019) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0208-2 · Cited by 125 · see citing works
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Günther, C., Rothhammer, V., Karow, M., Neurath, M., & Winner, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168870 · Cited by 123 · see citing works
Hegelmaier, T., Lebbing, M., Duscha, A., Tomaske, L., Tönges, L., Holm, J. B., Bjørn Nielsen, H., Gatermann, S. G., Przuntek, H., & Haghikia, A. (2020) · Cells · doi:10.3390/cells9020376 · Cited by 118 · see citing works
Self-citationThe microbiota–microglia axis in central nervous system disorders
Mossad, O., & Erny, D. (2020) · Brain Pathology · doi:10.1111/bpa.12908 · Cited by 98 · see citing works
Chen, H., Ma, X., Liu, Y., Ma, L., Chen, Z., Lin, X., Si, L., Ma, X., & Chen, X. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01662 · Cited by 96 · see citing works
Gut flora and metabolism are altered in epilepsy and partially restored after ketogenic diets
Gong, X., Cai, Q., Liu, X., An, D., Zhou, D., Luo, R., Peng, R., & Hong, Z. (2021) · Microbial Pathogenesis · doi:10.1016/j.micpath.2021.104899 · Cited by 91 · see citing works
Luk, B., Veeraragavan, S., Engevik, M., Balderas, M., Major, A., Runge, J., Luna, R. A., & Versalovic, J. (2018) · PLOS ONE · doi:10.1371/journal.pone.0196510 · Cited by 90 · see citing works
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Benedek, G., Zhang, J., Nguyen, H., Kent, G., Seifert, H. A., Davin, S., Stauffer, P., Vandenbark, A. A., Karstens, L., Asquith, M., et al. (2017) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2017.06.007 · Cited by 64 · see citing works
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- Authors
- Haghikia, A., Jörg, S., Duscha, A., Berg, J., Manzel, A., Waschbisch, A., Hammer, A., Lee, D.-H., May, C., Wilck, N., Balogh, A., Ostermann, A. I., Schebb, N. H., Akkad, D. A., Grohme, D. A., Kleinewietfeld, M., Kempa, S., Thöne, J., Demir, S., Müller, D. N., Gold, R., & Linker, R. A.
- Affiliations
- Ruhr University Bochum (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Max Delbrück Center (DE)
- University of Veterinary Medicine Hannover, Foundation (DE)
- University of Wuppertal (DE)
- Technische Universität Dresden (DE)
- Corresponding author
- Haghikia, Aiden
- Linker, Ralf A.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 43
- Issue
- 4
- Pages
- 817-829
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1941562583
- Semantic Scholar
- caf7fe00ebf43d42bff99639dd0f488702493788
- Cited by
- 927
- References
- 35
- Citations by year
- 2026: 54 · 2025: 103 · 2024: 109 · 2023: 99 · 2022: 122 · 2021: 110 · 2020: 89 · 2019: 77 · 2018: 73 · 2017: 58 · 2016: 28 · 2015: 4
- FWCI
- 26.73
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-04-19)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Novartis Foundation
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- dietary fatty acids, long-chain fatty acids, short-chain fatty acids, central nervous system autoimmunity, experimental autoimmune encephalomyelitis, multiple sclerosis, Th1 cells, Th17 cells, regulatory T cells, p38 MAPK pathway, JNK1, lamina propria, gut microbiota metabolites
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Liver X Receptors, Animals, Central Nervous System, Dietary Fats, Duodenum, Encephalomyelitis, Autoimmune, Experimental, Fatty Acids, Gene Expression Regulation, Lauric Acids, Molecular Weight, Spleen, Autoimmunity, T-Lymphocyte Subsets, Th1 Cells, MAP Kinase Signaling System, Lymphopoiesis, Receptors, G-Protein-Coupled, T-Lymphocytes, Regulatory, Mice, Orphan Nuclear Receptors, Th17 Cells, Transcriptome
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