Acetylated and butyrylated high amylose starch (HAMS-AB) is a prebiotic shown to be effective in type 1 diabetes (T1D) prevention in mouse models and is safe in adults with established T1D. HAMS-AB alters the gut microbiome profile with increased bacterial fermenters that produce short chain fatty acids (SCFAs) with anti-inflammatory and immune-modulatory effects. We performed a pilot study using a cross-over design to assess the safety and efficacy of 4 weeks of oral HAMS-AB consumption by recently diagnosed (< 2 years of diagnosis) youths with T1D. Seven individuals completed the study. The mean(SD) age was 15.0 (1.2) yrs., diabetes duration 19.5 (6.3) months, 5 of the 7 were female and 4/7 were White, all with a BMI of < 85th%. The prebiotic was safe. Following prebiotic intake, gut microbiome changes were seen, including a notable increase in the relative abundance of fermenters such as Bifidobacterium and Faecalibacterium. Treatment was also associated with changes in bacterial functional pathways associated with either improved energy metabolism (upregulation of tyrosine metabolism) or anti-inflammatory effects (reduced geraniol degradation). Stool SCFA analyses showed increased butyrate levels post-prebiotic [8.1(9.8) vs 22.6(6.4)mmol SCFA/kg fecal material, p=0.047]. Plasma metabolites associated with improved glycemia, such as hippurate, were significantly increased after treatment and there were positive and significant changes in the immune regulatory function of mucosal associated invariant T cells. There was a significant decrease in the area under the curve glucose but not C-peptide, as measured during a mixed meal tolerance testing, following the prebiotic consumption. In summary, the prebiotic HAMS-AB was safe in adolescents with T1D with positive and promising effects on the gut microbiome composition, function and immune regulatory function.

The authors have declared no competing interest.

NCT04114357

https://pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-023-01373-4

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 approved by Indiana University's Institutional Review Board on November 21st 2019 under protocol number 1907172784. The authors have obtained assent from participants and consent from their legal guardians to take part in the present study and with results being published.

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