Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and Beta-cell Function in Youth with Newly-Diagnosed Type 1 Diabetes: Protocol of a Randomized Controlled Trial

IntroductionData show that disturbances in the gut microbiota play a role in glucose homeostasis, type 1 diabetes (T1D) risk and progression. The prebiotic high amylose maize starch (HAMS) alters the gut microbiome profile and metabolites favorably with an increase in bacteria producing short chain fatty acids (SCFAs) that have significant anti-inflammatory effects. HAMS also improves glycemia, insulin sensitivity and secretion in healthy non-diabetic adults. Additionally, a recent study testing an acetylated and butyrylated form of HAMS (HAMS-AB) that further increases SCFA production prevented T1D in a rodent model without adverse safety effects. The overall objective of this human study will be to assess how daily HAMS-AB consumption impacts the gut microbiome profile, SCFA production, {beta}-cell heath, function and glycemia as well as immune responses in newly-diagnosed T1D youth. Methods and AnalysisWe hypothesize that HAMS-AB intake will improve the gut microbiome profile, increase SCFA production, improve {beta}-cell health, function and glycemia as well as modulate the immune system. We describe here a pilot, randomized crossover trial of HAMS-AB in 12 newly-diagnosed T1D youth with residual {beta}-cell function. In Aim 1, we will determine the effect of HAMS-AB on the gut microbiome profile and SCFA production; in Aim 2, we will determine the effect of HAMS-AB on {beta}-cell health, function and glycemia; and in Aim 3, we will determine the peripheral blood effect of HAMS-AB on frequency, phenotype and function of specific T cell markers. We anticipate beneficial effects from a simple, inexpensive, and safe dietary approach. Ethics and DisseminationThe Institutional Review Board at Indiana University approved the study protocol. The findings of this trial will be submitted to a peer-reviewed pediatric journal. Abstracts will be submitted to relevant national and international conferences. Trial registration numberNCT04114357; Pre-results. Article SummaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIThe study design (randomized controlled trial, RCT) is the most robust methodology to assess the effectiveness of therapeutic interventions. C_LIO_LIThe findings of this RCT, whether positive or negative, will contribute to the formulation of further recommendations on the use of high amylose maize starch that has been acetylated and butyrylated for improving beta-cell function in children with newly diagnosed type 1 diabetes (T1D). C_LI