Gut microbial differences are associated with and thought to contribute separately to obesity and to type 1 diabetes development. Obesity is increasingly prevalent in type 1 diabetes, creating management problems and higher rate of diabetes complications. To test how obesity may influence the gut microbiome, we analyzed stool samples for gut microbial and metabolite differences in lean (n=27, BMI: 5-85%) and obese (n=21, BMI: ≥95%) youth with type 1 diabetes. Participants were aged 15.3±2.2 y (42% female, 94% White), with A1c 7.8±1.3% and diabetes duration 5.1±4.4 y. Bacterial community analysis using metagenomic shotgun sequencing showed that within each BMI group, there were no differences in within sample species (α) diversity. There were significant dissimilarities in species (β) diversity between BMI groups (Fig 1A). Linear Discriminant Analysis Effect Size (LEfSe) showed a differential distribution of significantly abundant taxa in either the lean or obese groups (Fig. 1B). Functional profiling showed specific pathways are differentially enriched in the groups (Fig. 1C-D). Interestingly, stool short chain fatty acids (beneficial microbial metabolites) were higher in the obese compared to the lean group (p<0.05). This is a paradoxical finding that warrants further investigation.

In summary, our findings show links between the microbiome and metabolite composition, and obesity in type 1 diabetes and could lead to therapeutic targets in the gut.

Disclosure

H.M. Ismail: Consultant; Rise Therapeutics. D. Perera: None. R.K. Mandal: None. S. Javornik Cregeen: None. L. DiMeglio: Consultant; Abata Therapeutics, Vertex Pharmaceuticals Incorporated. Advisory Panel; Merck & Co., Inc. T.S. Hannon: Advisory Panel; Eli Lilly and Company. C. Evans-Molina: Advisory Panel; Provention Bio, Inc., DiogenX, Avotres Inc., Neurodon, MaiCell Therapeutics. Other Relationship; Isla Technology, Bristol-Myers Squibb Company, Nimbus Therapeutics. Research Support; Lilly, Astellas Pharma Inc. N. Schmidt: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK129799-01A1)

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