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Pediatr Diabetes. 2019 May 12. doi: 10.1111/pedi.12865. [Epub ahead of print]

Gut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes : a prospective cohort study.

Author information

1
Women's & Children's Hospital, South Australia.
2
Robinson Research Institute, University of Adelaide, South Australia.
3
Walter and Eliza Hall Institute of Medical Research, Victoria.
4
CSIRO, Health and Biosecurity, South Australia.
5
Department of Medical Biology, University of Melbourne.
6
Royal Melbourne Hospital, Victoria.
7
The Children's Hospital at Westmead & University of Sydney, New South Wales.
8
Harry Perkins Institute of Medical Research, Western Australia.

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 analysed 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% CI 1.21, 9.07, p=0.006), lower within-sample (alpha) microbial diversity (31.3 [11.2], 95% CI 9.3, 53.3, p=0.005), and lower abundance of SCFA-producing bacteria. Alpha diversity (observed richness) correlated with plasma acetate levels in all groups combined (regression coeff [SE] 0.57 [0.21], 95% CI 0.15, 0.99 p=0.008).

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. This article is protected by copyright. All rights reserved.

KEYWORDS:

Gut microbiome; Intestinal permeability; Islet autoimmunity; Short chain fatty acids; Type 1 diabetes

PMID:
31081243
DOI:
10.1111/pedi.12865

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