Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/119605
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Type: Journal article
Title: Gut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes: a prospective cohort study
Author: Harbison, J.
Roth-Schulze, A.
Giles, L.
Tran, C.
Ngui, K.
Penno, M.
Thomson, R.
Wentworth, J.
Colman, P.
Craig, M.
Morahan, G.
Papenfuss, A.
Barry, S.
Harrison, L.
Couper, J.
Citation: Pediatric Diabetes, 2019; 20(5):574-583
Publisher: Wiley Online Library
Issue Date: 2019
ISSN: 1399-543X
1399-5448
Statement of
Responsibility: 
Lynne C. Giles, Cuong D. Tran ... Megan A. Penno, Rebecca L. Thomson ... Simon C Barry ... Jennifer J. Couper ... et al.
Abstract: AIMS/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.
Keywords: gut microbiome; intestinal permeability; islet autoimmunity; short chain fatty acids; type 1 diabetes
Rights: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
RMID: 0030114951
DOI: 10.1111/pedi.12865
Appears in Collections:Paediatrics publications

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