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 IP, glucose tolerance and intestinal bacteria in human type 2 diabetes. In all, twenty-nine men with well-controlled type 2 diabetes were randomised to a prebiotic (galacto-oligosaccharide mixture) or placebo (maltodextrin) supplement (5·5 g/d 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 intravenous glucose tolerance test. 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. The current study does not provide evidence for the role of prebiotics in the treatment of type 2 diabetes.

Type 2 diabetes (T2D) has been linked with increased intestinal permeability, but the clinical significance of this phenomenon remains unknown. The objective of this study was to investigate the potential link between glucose control, intestinal permeability, diet and intestinal microbiota in patients with T2D. Thirty‐two males with well‐controlled T2D and 30 age‐matched male controls without diabetes were enrolled in a case–control study. Metabolic parameters, inflammatory markers, endotoxemia, and intestinal microbiota in individuals subdivided into high (HP) and normal (LP) colonic permeability groups, were the main outcomes. In T2D, the HP group had significantly higher fasting glucose (P = 0.034) and plasma nonesterified fatty acid levels (P = 0.049) compared with the LP group. Increased colonic permeability was also linked with altered abundances of selected microbial taxa. The microbiota of both T2D and control HP groups was enriched with Enterobacteriales. In conclusion, high intestinal permeability was associated with poorer fasting glucose control in T2D patients and changes in some microbial taxa in both T2D patients and nondiabetic controls. Therefore, enrichment in the gram‐negative order Enterobacteriales may characterize impaired colonic permeability prior to/independently from a disruption in glucose tolerance.

The effect of maternal low protein diet in pregnancy on the function of offspring cerebral cytochrome c oxidase (CcO) was investigated in vitro immediately before and after birth, using fetal and neonatal rat pup forebrain tissue. Pregnant rat dams were fed either a control (C, 18% casein n = 22) or low protein (LP, 9% casein n = 14) diet. Cerebral tissues were harvested from pups the day before (E21) and after (P1) birth. A Clarke electrode chamber was used to determine O 2 consumption in brain tissue homogenate, under baseline conditions with and without the mitochondrial electron transport chain inhibitor myxothiazol and in the presence of incremental doses of the electron donor N ',N ',N ',N '-tetramethyl-p-phenylenediamide (TMPD) with myxothiazol. Maximal stimulated CcO activity (V O 2 max ) was less in LP versus C pups at both E21 (P < 0.001) and P1 (P < 0.05). At E21 only, sensitivity to electron flux (pEC 50 ) was greater (P < 0.001) in LP compared to C offspring. In addition,V O 2 max was reduced and pEC 50 was greater after birth (i.e. P1 versus E21) in C (P < 0.001) but not in LP pups. This is the first report of the effects of maternal dietary imbalance in pregnancy on offspring cerebral metabolic function. The effects may form part of a developmental adaptive response to reduce energy consumption and promote perinatal survival, or to confer advantage in a postnatal environment predicted to be nutritionally poor.

Aberrant microbiota composition and function have been linked to several intestinal and systemic pathologies, including obesity, the metabolic syndrome and type 2 diabetes (1) . In animal models, prebiotics improve glucose tolerance which may be linked to concurrent favourable changes in the intestinal microbiota, intestinal permeability and endotoxaemia (2) . This is the first study to investigate the link between intestinal permeability, glucose tolerance, and intestinal bacteria in human type 2 diabetes. 30 males with well-controlled type 2 diabetes were randomised to a prebiotic, galacto-oligosaccharide (GOS, 5 g/day), or placebo (maltodextrin) supplementation for 12 weeks. Glucose tolerance, intestinal permeability, endotoxaemia, inflammatory markers and intestinal bacterial composition were assessed at baseline and post-intervention. Intestinal permeability was measured by urinary excretion of 51 Cr-EDTA and glucose tolerance by insulin modified IVGTT. Gut microbial community analysis was performed by high-throughput Next-Generation Sequencing of 16S rRNA amplicons and quantitative PCR.GOS had no significant effects on glucose tolerance, intestinal permeability or inflammatory markers compared with placebo. Non-metric Multi-dimensional Scaling analysis suggested GOS affected intestinal bacterial composition differently to the placebo; however, there were no significant differences in bacterial abundances between treatment groups at any taxonomic level. Nevertheless, changes in the bacterial family Veillonellaceae correlated inversely with glucose response (r = −0·90, P = 0·042) and IL-6 (r = −0·90, P = 0·042) in the GOS group. Changes in fasting serum lipopolysaccharide binding protein concentration correlated with fasting blood glucose (r = 0·79, P = 0·0026) in the placebo group.Lack of effect of GOS in this study may be due to the low dose and the short duration of the supplementation, although concurrent metformin treatment may have masked the effects of GOS. Furthermore, whilst the high heterogeneity of human diabetes compared to animal models may also have played a 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. However, the small sample size was a limitation of this study.