PracticeUpdate: Conference Series | ADC 2018

Research Uncovers Potential Role of Gut Microbiome in T1D Pathogenesis BY THE PRACTICEUPDATE EDITORIAL TEAM

A n "unbalanced" gut microbiome may play a role in the pathogenesis of type 1 diabetes (T1D), say research- ers who found that children with islet autoimmunity or T1D had gut dysbiosis. They also discovered that children who presented with islet autoantibodies, who then progressed to T1D, had increased intestinal permeability compared with those who did not progress to T1D. " The discovery of a low abundance of anti- inflammatory species in type 1 diabetes and at-risk children require deeper sequencing to look at the potential for bespoke probiotic development to reduce the progression rate to T1D. " This longitudinal study was the first to characterize the gut microbiome and small intestinal permeability in Southern Hemisphere children with multiple islet autoantibodies and T1D, said Professor Jennifer Couper, Head of Paediatrics at the University of Adelaide in Adelaide, South Australia. “Intestinal permeability was previously shown to be high in type 1 diabetes … but what hadn’t previously been shown is that intestinal permeability is higher in patients who progressed to diabetes” than those who did not progress to dia- betes, Professor Couper said.

Professor Couper and her colleagues followed a small cohort of 88 children every 6 months for a median of 13 months (range, 2–34 months) to characterize gut microbiome, bacterial products, and small intestinal permeability in children with islet autoimmunity. Of these children, 18 had islet autoim- munity, while 29 had recent-onset T1D. The study included 41 age- and gen- der-matched unrelated or sibling controls. Participants’ stool samples were collected for 16S rRNA gene sequencing. Small intestinal permeability was measured using the blood lactulose:rhamnose (L/R) ratio 90 minutes after drinking a 5% lac- tulose/1% rhamnose solution. A higher L/R ratio indicates higher permeability. Short-chain fatty acids were measured by gas chromatography, and checks for progression to T1D were performed using a glucose tolerance test or postprandial glucose test every 6 months. The partici- pants’ dietary intake was evaluated using the Australian Child and Adolescent Food Frequency Questionnaire.

In terms of the gut microbiome, the alpha diversity (ie, the diversity within a sample) showed no differences among children with islet autoimmunity, T1D, and controls. However, children with two or more islet antibodies who progressed to T1D ("progressors") had lower alpha diversity (observed richness) and different beta diversity (ie, a measure of the dissimilar- ity between each sample pair) compared with those who did not progress to T1D ("non-progressors"). The relative abundance of bacteria showed there was a deficit in the anti-in- flammatory bacteria Butyricimonas and Prevotella in children with two or more islet antibodies or T1D. There was no sig- nificant difference in diet that could have explained the difference in bacteria. Progressors also had a higher L/R ratio than non-progressors. Lower alpha diver- sity related weakly to a higher L/R ratio. To the researchers’ surprise, plasma acetate – a short-chain fatty acid – was related to lower observed richness.

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