Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/119605
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dc.contributor.authorHarbison, J.E.-
dc.contributor.authorRoth-Schulze, A.J.-
dc.contributor.authorGiles, L.C.-
dc.contributor.authorTran, C.D.-
dc.contributor.authorNgui, K.M.-
dc.contributor.authorPenno, M.A.-
dc.contributor.authorThomson, R.L.-
dc.contributor.authorWentworth, J.M.-
dc.contributor.authorColman, P.G.-
dc.contributor.authorCraig, M.E.-
dc.contributor.authorMorahan, G.-
dc.contributor.authorPapenfuss, A.T.-
dc.contributor.authorBarry, S.C.-
dc.contributor.authorHarrison, L.C.-
dc.contributor.authorCouper, J.J.-
dc.date.issued2019-
dc.identifier.citationPediatric Diabetes, 2019; 20(5):574-583-
dc.identifier.issn1399-543X-
dc.identifier.issn1399-5448-
dc.identifier.urihttp://hdl.handle.net/2440/119605-
dc.description.abstractAIMS/HYPOTHESIS:To investigate the longitudinal relationship between the gut microbiome, circulating short chain fatty acids (SCFAs) and intestinal permeability in children with islet autoimmunity or type 1 diabetes and controls. METHODS:We analyzed the gut bacterial microbiome, plasma SCFAs, small intestinal permeability and dietary intake in 47 children with islet autoimmunity or recent-onset type 1 diabetes and in 41 unrelated or sibling controls over a median (range) of 13 (2-34) months follow-up. RESULTS:Children with multiple islet autoantibodies (≥2 IA) or type 1 diabetes had gut microbiome dysbiosis. Anti-inflammatory Prevotella and Butyricimonas genera were less abundant and these changes were not explained by differences in diet. Small intestinal permeability measured by blood lactulose:rhamnose ratio was higher in type 1 diabetes. Children with ≥2 IA who progressed to type 1 diabetes (progressors), compared to those who did not progress, had higher intestinal permeability (mean [SE] difference +5.14 [2.0], 95% confidence interval [CI] 1.21, 9.07, P = .006), lower within-sample (alpha) microbial diversity (31.3 [11.2], 95% CI 9.3, 53.3, P = .005), and lower abundance of SCFA-producing bacteria. Alpha diversity (observed richness) correlated with plasma acetate levels in all groups combined (regression coefficient [SE] 0.57 [0.21], 95% CI 0.15, 0.99 P = .008). CONCLUSIONS/INTERPRETATION:Children with ≥2 IA who progress to diabetes, like those with recent-onset diabetes, have gut microbiome dysbiosis associated with increased intestinal permeability. Interventions that expand gut microbial diversity, in particular SCFA-producing bacteria, may have a role to decrease progression to diabetes in children at-risk.-
dc.description.statementofresponsibilityLynne C. Giles, Cuong D. Tran ... Megan A. Penno, Rebecca L. Thomson ... Simon C Barry ... Jennifer J. Couper ... et al.-
dc.language.isoen-
dc.publisherWiley Online Library-
dc.rights© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.-
dc.source.urihttp://dx.doi.org/10.1111/pedi.12865-
dc.subjectgut microbiome-
dc.subjectintestinal permeability-
dc.subjectislet autoimmunity-
dc.subjectshort chain fatty acids-
dc.subjecttype 1 diabetes-
dc.titleGut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes: a prospective cohort study-
dc.typeJournal article-
dc.identifier.doi10.1111/pedi.12865-
dc.relation.grantNHMRC-
pubs.publication-statusPublished-
dc.identifier.orcidGiles, L.C. [0000-0001-9054-9088]-
dc.identifier.orcidTran, C.D. [0000-0001-9220-2715]-
dc.identifier.orcidPenno, M.A. [0000-0002-9617-0826]-
dc.identifier.orcidThomson, R.L. [0000-0002-7807-4144]-
dc.identifier.orcidBarry, S.C. [0000-0002-0597-7609]-
dc.identifier.orcidCouper, J.J. [0000-0003-4448-8629]-
Appears in Collections:Aurora harvest 4
Paediatrics publications

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