We aimed to characterise the gut microbiome and small intestinal permeability in children with islet autoimmunity and type 1 diabetes (T1D). 88 participants, median age 11.8 (IQR 8.1-13.3) years at baseline were followed 6 monthly for a median of 13 months (range 2-34). 18 had islet autoimmunity, 29 recent-onset T1D, and 41 were age and gender-matched unrelated or sibling controls. Stool samples were collected (Omnigene kit) for 16S rRNA gene sequencing. Small intestinal permeability was measured by blood lactulose:rhamnose ratio (L/R), 90 minutes after drinking a 5gm lactulose/1gm rhamnose solution. Antibodies to insulin, GAD, IA2 and ZnT8 were assayed using IASP standardized radiobinding assays. Statistical analysis used linear mixed models. Differential abundance analysis used limma with total-sum scaling.

Children with islet autoimmunity or T1D had gut microbiome dysbiosis with reduced α diversity and different β diversity compared with controls. Progressors from islet autoimmunity to T1D had lower observed richness (OTUs) (p=0.01) and different β diversity (Adonis, P=0.004), compared with non-progressors. Genus Prevotella, with anti-inflammatory properties, was less abundant in children with T1D (p<0.005) or ≥ 2 islet antibodies (p<0.005) than in controls. Diet did not explain this difference. L/R was higher in T1D than sibling controls (mean difference +3.03±1.02, p=0.003). Progressors had higher L/R than non-progressors (+4.74±1.97, p=0.01) and sibling controls (+4.62±1.69, p=0.006). There was a trend towards a relationship between higher L/R and lower observed richness in the microbiome over time in children with ≥ 2 islet antibodies or T1D (coeff -0.0617, 95% CI -0.1254, 0.002 P=0.058).

Australian children progressing from islet autoimmunity to T1D have gut dysbiosis and increased intestinal permeability. This observation supports a mechanism underlying progression to T1D.


J.E. Harbison: None. A.J. Roth-Schulze: None. S.C. Barry: None. C.D. Tran: None. K. Ngui: None. M.A. Penno: None. J. Wentworth: None. P.G. Colman: None. R. Thomson: None. M.E. Craig: None. A.T. Papenfuss: None. L. Giles: None. L.C. Harrison: None. J. Couper: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.