Background
Studies in animal models and humans with type 1 diabetes mellitus (T1DM) have shown that probiotic supplementation leads to decreased pro‐inflammatory cytokines (responsible for damaging β‐cells of the pancreas), improved gut barrier function, and induction of immune tolerance.
Objective
To study the effect of supplementation of probiotics in children with T1DM on glycemic control, insulin dose, and plasma C‐peptide levels.
Methods
A single‐centered, double‐blinded, and randomized placebo‐controlled pilot trial was conducted in children (2–12 years) with new‐onset T1DM. Ninety‐six children were randomized and allocated to Placebo or Intervention groups. The intervention included high dose (112.5 billion viable lyophilized bacteria per capsule) multi‐strain probiotic De Simone formulation (manufactured by Danisco‐Dupont) sold as Visbiome® in India. The probiotic was supplemented for 3 months and HbA1c, fasting C‐peptide, blood sugar records, and insulin dose was recorded at baseline and 3 months.
Results
A total of 90 patients (45 in each group) were analyzed for outcome parameters. We found a significant decrease in HbA1c (5.1 vs. 3.8; p = 0.021) and a significant decline in total and bolus insulin dose (U/kg/day; p = 0.037 and 0.018, respectively) in the intervention group when compared with the placebo group. A significantly higher (p = 0.023) number of children achieved remission in the treatment group. We did not notice adverse effects in either of the study groups.
Conclusion
Children with newly diagnosed T1DM managed with standard treatment along with probiotics showed better glycemic control and a decrease in insulin requirements; however, more extensive studies are further warranted.
Type-1 diabetes (T1D) is an autoimmune disease caused by progressive loss of insulin-producing beta cells in the pancreas. Butyrate is a commensal microbial-derived metabolite, implicated in intestinal homeostasis and immune regulation. Here, we investigated the mechanism of diabetes remission in non-obese diabetic (NOD) mice following butyrate administration. Sodium butyrate (150 mM) was administered to female NOD mice in drinking water after the onset of hyperglycemia (15–25 weeks age) and at 4 weeks of age (early-intervention group). Butyrate administration reduced the progression of hyperglycemia in diabetic mice and delayed onset of diabetes in the early-intervention group with a reduction in insulitis. Butyrate administration increased regulatory T cells (Tregs) in the colon, mesenteric lymph nodes, Peyer’s patches, and its protective effects diminished upon depletion of Tregs. Further, an increase in α4β7, CCR9, and GPR15 expressing Tregs in the pancreatic lymph nodes (PLN) and pancreas in butyrate-treated mice suggested migration of gut-primed Tregs towards the pancreas. Finally, the adoptive transfer experiments demonstrated that induced Tregs from gut-associated lymphoid tissue can migrate towards the pancreas and PLN and delay the onset of diabetes. Our results thus suggest that early administration of butyrate can restore immunological tolerance during T1D via induction of Tregs with migratory capabilities.
Our study shows that PPI-specific CD8+ T cells can be detected in both JOT1D and AOT1D subjects over a period of time with reliable consistency in frequency but variable pathophysiological characteristics. Insulin therapy seems to reduce the PPI-specific T subsets; however, the PPI-specific T cells continue to persist as attractive targets for immunotherapy.
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