Abstract
Aberrant microbiota composition and function have been linked to several pathologies, including type 2 diabetes. In animal models, prebiotics induce favourable changes in the intestinal microbiota, intestinal permeability (IP) and endotoxaemia which are linked to concurrent improvement in glucose tolerance. This is the first study to investigate the link between intestinal permeability, glucose tolerance, and intestinal bacteria in human type 2 diabetes. Twenty-nine males with well-controlled type 2 diabetes were randomised to a prebiotic (galactooligosaccharide mixture) or placebo (maltodextrin) supplement (5.5g/day for 12 weeks). Intestinal microbial community structure, IP, endotoxaemia, inflammatory markers and glucose tolerance were assessed at baseline and post-intervention. IP was estimated by the urinary recovery of oral 51Cr-EDTA and glucose tolerance by insulin modified IVGTT. Intestinal microbial community analysis was performed by high-throughput Next-Generation Sequencing of 16S rRNA amplicons and quantitative PCR. Prebiotic fibre supplementation had no significant effects on clinical outcomes or bacterial abundances compared with placebo; however, changes in the bacterial family Veillonellaceae correlated inversely with changes in glucose response and IL-6 levels (r = -0.90, P = 0.042 for both) following prebiotic intake. The absence of significant changes to the microbial community structure at a prebiotic dosage/length of supplementation shown to be effective in healthy individuals is an important finding, We propose that concurrent metformin treatment and the high heterogeneity of human type 2 diabetes may have played a significant role. It is also plausible that prebiotics may play a more important role in prevention rather than in the treatment of human type 2 diabetes.