Obesity is increasingly prevalent in type 1 diabetes (T1D) and is associated with management problems and higher risk for diabetes complications. Gut microbiome changes have been described separately in each of T1D and obesity, however, it is unknown to what extent gut microbiome changes are seen when obesity and T1D concomitantly occur. Objective: To describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized significant gut microbial and metabolite differences between T1D youth who are lean (BMI: 5-<85%) vs. those with obesity (BMI: ≥95%). Methods: We analyzed stool samples for gut microbial (using metagenomic shotgun sequencing) and short-chain fatty acid (SCFA) metabolite differences in lean (n=27) and obese (n=21) T1D youth. The mean+/-SD age was 15.3+/-2.2yrs, A1c 7.8+/-1.3%, diabetes duration 5.1+/-4.4yrs, 42.0% females, and 94.0% were White. Linear discriminant analysis (LDA) effect size (LEfSe) was used to identify taxa that best discriminated between the BMI groups. Results: Bacterial community composition showed differences in species type (β-diversity) by BMI group (p=0.013). At the genus level, there was a higher ratio of Prevotella to Bacteroides in the obese group (p=0.0058). LEfSe analysis showed a differential distribution of significantly abundant taxa in either the lean or obese groups, including increased relative abundance of Prevotella copri, among other taxa in the obese group. Functional profiling showed that pathways associated with decreased insulin sensitivity were upregulated in the obese group. Stool SCFAs (acetate, propionate and butyrate) were higher in the obese compared to the lean group (p<0.05 for all). Conclusions: Our findings identify gut microbiome, microbial metabolite and functional pathways differences associated with obesity in T1D. These findings could be helpful in identifying gut microbiome targeted therapies to manage obesity in T1D.

The authors have declared no competing interest.

This study received support from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, Grant Numbers, KL2TR002530 (A Carroll, PI), and UL1TR002529 (A. Shekhar, PI). We also acknowledge support from the Board of Directors of the Indiana University Health Values Fund for Research Award and the Indiana Clinical and Translational Sciences Institute funded, in part by Grant U54TR002529 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award; the Indiana Clinical and Translational Sciences Institute funded, in part by Award Number ULITR002529 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award; the Pilot and Feasibility Grant from the Indiana Center for Diabetes and Metabolic Diseases (P30DK097512); the National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under Award Number K23DK129799, the Doris Duke Charitable Foundation through the COVID‐19 Fund to Retain Clinical Scientists Collaborative Grant Program (Grant 2021258) and The John Templeton Foundation (Grant 62288). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funding agencies.

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This study was reviewed by the Indiana University Institutional Review Board who approved the protocol, number 1908640459.

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