Prebiotics May Improve Outcomes in Children with Type 1 Diabetes

A recent study displayed improvements in diabetic markers including C-peptide and gut microbiota from treatment with prebiotics versus placebo over a 3-month study period.

A recent study identified the positive impact prebiotics may have on patients with type 1 diabetes. Study results were published in The Journal of Clinical Endocrinology & Metabolism.

Current therapy for patients with type 1 diabetes revolves around multiple daily doses of insulin accompanied by around-the-clock glucose monitoring. An oral supplement that could aid in glycemic control would be of great value to millions of patients.

Prebiotics are a type of fiber that can be considered as “food” for probiotics in the gut, which together encourage a healthy microbiome to support digestion and immunity. Previous studies have shown that patients with type 1 diabetes have an altered gut microbiota, or dysbiosis, that can potentially be harming glycemic control and intestinal permeability and therefore reducing insulin sensitivity. More specifically, patients with type 1 diabetes have displayed lower abundance of Bifidobacterium and higher abundance of Gram-negative bacteria. Evidence from animal studies has shown that a dysbiotic gut microbiota generates high levels of lipopolysaccharides (LPS) which causes inflammation of the intestinal mucosa, loss of tight junction integrity between epithelial cells, and increased intestinal permeability. Under this condition, LPS will cross the epithelium and enter circulation causing systemic inflammation, insulin resistance and poor glycemic control. Studies have also shown that type 1 diabetes is linked to increased intestinal permeability, which may encourage disease progression, systemic inflammation and poor metabolic control. The purpose of this trial was to determine the effect of prebiotics on glycemic control, gut microbiota and intestinal permeability in children with type 1 diabetes.

This single center, randomized, double-blind, placebo-controlled study recruited 38 children aged 8 to 17 years old from a tertiary care diabetes clinic in Canada. Participants must have been diagnosed with type 1 diabetes for at least 12 months but were excluded if A1C was greater than 10% in the previous 6 months, or if they had a chronic medical condition that could alter the gut microbiota (Crohn’s disease, cystic fibrosis, irritable bowel disease). Participants were randomized 1:1 to prebiotic (oligofructose-enriched inulin 8g orally/day) or placebo group (maltodextrin 3.3 g orally/day). The treatment period lasted 12 weeks, followed by a 12-week washout period. Data was collected at baseline, 3 months and 6 months, including: C-peptide, A1C, serum inflammatory markers (IL-6, IFN-gamma, TNF-alpha, and IL-10), GLP1, GLP2, intestinal permeability test by measurement of urine lactose to mannitol ratio, and stool samples for bacterial DNA analyses.

The prebiotic group showed a significant preservation in C-peptide protein levels during the 3-month intervention period while the placebo group showed a drop in C-protein levels. Intestinal permeability test displayed a decrease in the prebiotic group, whereas the placebo group showed an increase in intestinal permeability, although statistically nonsignificant (p=0.076). Regarding gut microbiota, the prebiotic group showed a significant increase in Bifidobacterium and Actinobacteria and Coriobacteriales. At 3 months, placebo had significantly higher relative abundance of Streptococcus, Roseburia inulinovorans, Terrisporobacter and Faecalitalea, compared to prebiotic. The bacterial presence in the placebo group did not remain after the 3-month washout period, whereas the prebiotic group continued to show increase in Coriobacteriales over placebo. All other measures did not show significant differences.

Although there was no observed decrease in A1C within this study, the preservation of C-peptide shows potential increased beta cell function which could lead to improved glycemic control, long-term. With a short duration of intervention of only 3 months, it is probable that the study period was not long enough to show a change in A1C. With evidence from animal studies suggesting improved insulin sensitivity, increased beta-cell proliferation and pancreatic insulin content, and increase in fecal Bifidobacterium from oral prebiotic therapy, this study further supports prebiotics’ potential for benefit in human patients with type 1 diabetes. Further studies with longer duration of intervention and larger population size, including adult patients, should be conducted.

Practice Pearls:

• A recent study on children with type 1 diabetes displayed a potential for improvement in glycemic control by a significant decrease in C-peptide and alteration of gut microbiota.
• Further studies with larger population size and longer duration of intervention need to be conducted to conclude the clinical correlation between prebiotics and type 1 diabetes progression and glycemic control.
• Prebiotic treatment may be a promising adjunctive treatment for glycemic control in patients with type 1 diabetes.

Ho, Josephine, et al. “Effect of Prebiotic on Microbiota, Intestinal Permeability and Glycemic Control in Children with Type 1 Diabetes.” The Journal of Clinical Endocrinology & Metabolism, 2019, doi:10.1210/jc.2019-00481.

Amber Satz, PharmD Candidate, LECOM School of Pharmacy