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Gut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes: A prospective cohort study
Author(s) -
Harbison Jessica E.,
RothSchulze Alexandra J.,
Giles Lynne C.,
Tran Cuong D.,
Ngui Katrina M.,
Penno Megan A.,
Thomson Rebecca L.,
Wentworth John M.,
Colman Peter G.,
Craig Maria E.,
Morahan Grant,
Papenfuss Anthony T.,
Barry Simon C.,
Harrison Leonard C.,
Couper Jennifer J.
Publication year - 2019
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.12865
Subject(s) - intestinal permeability , dysbiosis , type 1 diabetes , microbiome , medicine , autoimmunity , gut flora , immunology , diabetes mellitus , type 2 diabetes , endocrinology , islet , gastroenterology , physiology , biology , immune system , bioinformatics
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.