{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:02:54Z","timestamp":1790244174401,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T00:00:00Z","timestamp":1519689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01ES019313"],"award-info":[{"award-number":["R01ES019313"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01MH094755"],"award-info":[{"award-number":["R01MH094755"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI123947"],"award-info":[{"award-number":["R01AI123947"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI129788"],"award-info":[{"award-number":["R01AI129788"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01AT003961"],"award-info":[{"award-number":["P01AT003961"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103641"],"award-info":[{"award-number":["P20GM103641"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AT006888"],"award-info":[{"award-number":["R01AT006888"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The importance of the gut microbiome in the regulation of non\u2010infectious diseases has earned unprecedented interest from biomedical researchers. Widespread use of next\u2010generation sequencing techniques has prepared a foundation for further research by correlating the presence of specific bacterial species with the onset or severity of a disease state, heralding paradigm\u2010shifting results. This review covers the mechanisms through which a dysbiotic gut microbiota contributes to the pathological symptoms in an autoimmune neurodegenerative disorder, multiple sclerosis (<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>). Although the central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) is protected by the blood\u2013brain barrier (<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>), it is unclear how gut dysbiosis can trigger potential immunological changes in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> in the presence of the <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>. This review focuses on the immunoregulatory functionality of microbial metabolites, which can cross the <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> and mediate their effects directly on immune cells within the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> and\/or indirectly through modulating the response of peripheral T cells to stimulate or inhibit pro\u2010inflammatory chemokines and cytokines, which in turn regulate the autoimmune response in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>. Although more research is clearly needed to directly link the changes in gut microbiome with neuroinflammation, focusing research on microbiota that produce beneficial metabolites with the ability to attenuate chronic inflammation systemically as well as in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>, can offer novel preventive and therapeutic modalities against a wide array of inflammatory and autoimmune diseases.<\/jats:p>","DOI":"10.1111\/imm.12903","type":"journal-article","created":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T08:42:41Z","timestamp":1517560961000},"page":"178-185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["The role of gut microbiome and associated metabolome in the regulation of neuroinflammation in multiple sclerosis and its implications in attenuating chronic inflammation in other inflammatory and autoimmune disorders"],"prefix":"10.1111","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-2089","authenticated-orcid":false,"given":"Nicholas","family":"Dopkins","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology University of South Carolina School of Medicine Columbia SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash S.","family":"Nagarkatti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology University of South Carolina School of Medicine Columbia SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitzi","family":"Nagarkatti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology University of South Carolina School of Medicine Columbia SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000094"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2010.04143.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1501s77"},{"key":"e_1_2_10_5_1","first-page":"51275","article-title":"Myelin oligodendrocyte glycoprotein (MOG35\u201055) induced experimental autoimmune encephalomyelitis (EAE) in C57BL\/6 mice","volume":"86","author":"Bittner S","year":"2014","journal-title":"J Vis Exp"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCP7UBK8IBVMVNR"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00531"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.09.025"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002502"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2343"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.9.4712"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11550"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179017"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2515"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.5223\/pghn.2016.19.4.221"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.017"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.011"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12331"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0884533611436116"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01096"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1128\/aem.39.2.453-455.1980","article-title":"Sulfide production from cysteine by Desulfovibrio desulfuricans","volume":"39","author":"Forsberg CW","year":"1980","journal-title":"Appl Environ Microbiol"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13026"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2009.112"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.09.008"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517711568"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.110.003483"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/708659"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0881fje"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00175-1"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws012"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.113.091165"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.064139-0"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501727"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukarGeneExpr.v18.i3.20"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr218"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023522"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxt011"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03054.x"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06880"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06881"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2013.04.016"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4106"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079819"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mn.7800190"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.15.2125"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173032"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12726"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12721"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.44"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241165"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2009.07.006"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2012.158"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2014.14.6.277"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137429"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646792"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-13-0079"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2015.12.008"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11276"},{"key":"e_1_2_10_59_1","first-page":"78","article-title":"Complementary and alternative medicine in multiple sclerosis","volume":"16","author":"Bowling AC","year":"2010","journal-title":"Continuum (Minneap Minn)"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.52.1.18"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.93"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.11.015"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.04.006"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-9-S1-S3"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1159\/000097202"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211798220918"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(93)90027-V"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00966020"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114666"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2009.09.001"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009759"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4611"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12903","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12903","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T11:32:05Z","timestamp":1694691125000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12903"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,27]]},"references-count":71,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/imm.12903"],"URL":"https:\/\/doi.org\/10.1111\/imm.12903","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,27]]},"assertion":[{"value":"2017-11-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}