Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/106159
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dc.contributor.authorMariño, E.en
dc.contributor.authorRichards, J.en
dc.contributor.authorMcLeod, K.en
dc.contributor.authorStanley, D.en
dc.contributor.authorYap, Y.en
dc.contributor.authorKnight, J.en
dc.contributor.authorMcKenzie, C.en
dc.contributor.authorKranich, J.en
dc.contributor.authorOliveira, A.en
dc.contributor.authorRossello, F.en
dc.contributor.authorKrishnamurthy, B.en
dc.contributor.authorNefzger, C.en
dc.contributor.authorMacia, L.en
dc.contributor.authorThorburn, A.en
dc.contributor.authorBaxter, A.en
dc.contributor.authorMorahan, G.en
dc.contributor.authorWong, L.en
dc.contributor.authorPolo, J.en
dc.contributor.authorMoore, R.en
dc.contributor.authorLockett, T.en
dc.contributor.authoret al.en
dc.date.issued2017en
dc.identifier.citationNature Immunology, 2017; 18(5):552-562en
dc.identifier.issn1529-2908en
dc.identifier.issn1529-2916en
dc.identifier.urihttp://hdl.handle.net/2440/106159-
dc.description.abstractGut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance. Feeding mice a combined acetate- and butyrate-yielding diet provided complete protection, which suggested that acetate and butyrate might operate through distinct mechanisms. Acetate markedly decreased the frequency of autoreactive T cells in lymphoid tissues, through effects on B cells and their ability to expand populations of autoreactive T cells. A diet containing butyrate boosted the number and function of regulatory T cells, whereas acetate- and butyrate-yielding diets enhanced gut integrity and decreased serum concentration of diabetogenic cytokines such as IL-21. Medicinal foods or metabolites might represent an effective and natural approach for countering the numerous immunological defects that contribute to T cell-dependent autoimmune diseases.en
dc.description.statementofresponsibilityEliana Mariño, James L Richards, Keiran H McLeod, Dragana Stanley, Yu Anne Yap, Jacinta Knight, Craig McKenzie, Jan Kranich, Ana Carolina Oliveira, Fernando J Rossello, Balasubramanian Krishnamurthy, Christian M Nefzger, Laurence Macia, Alison Thorburn, Alan G Baxter, Grant Morahan, Lee H Wong, Jose M Polo, Robert J Moore, Trevor J Lockett, Julie M Clarke, David L Topping, Leonard C Harrison, Charles R Mackayen
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rights© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.en
dc.subjectGastrointestinal microbiome; autoimmunityen
dc.titleGut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetesen
dc.typeJournal articleen
dc.identifier.rmid0030067725en
dc.identifier.doi10.1038/ni.3713en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1016953en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/606947en
dc.identifier.pubid345182-
pubs.library.collectionMolecular and Biomedical Science publicationsen
pubs.library.teamDS14en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Molecular and Biomedical Science publications

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