Fecal Enterobacteriales enrichment is associated with increased in vivo intestinal permeability in humans

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

Host-microbiome interactionsin human type 2 diabetes following prebiotic fibre (galactooligosaccharide) intake

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

Gut microbiota in human type 2 diabetes : in-vivo and in-vitro studies.

The gut microbiota plays an important role in the development of type 2 diabetes (T2D), which is an alteration in the diversity and abundance of the gut microbiota, favouring the growth of Gram-negative bacteria. Although a lot of studies have shown this to be the case, most of this work has been done in animal models with few studies in humans. In animal models of T2D, it is known that a high-fat diet alters the gut microbiota in favour of the growth of Gram–negative bacteria. The outer membrane of Gram-negative bacteria contains lipopolysaccharide (LPS) which is an endotoxin that can trigger inflammation leading to metabolic disorders such insulin resistance and T2D, hence T2D is considered a low grade inflammatory disorder. In this thesis, the effect of Galactooligosaccharide (GOS), a prebiotic, on the composition of the gut microbiota was investigated. Next generation sequencing (NGS) of the gut microbiota of T2D and healthy control subjects showed no significant difference at the phylum level between the two groups. Furthermore, T2D patients in the prebiotic group had a significant increase in the level of Firmicutes compared to the placebo group. Also, although not significant, T2D patients on metformin had increased level of Bacteroidetes, Proteobacteria and Actinobacteria compared to those not on metformin. The ability of human faecal water (FW) to distinguish between healthy and T2D patients using an in vitro model of the intestinal mucosa was studied. FW from T2D patients decreased Caco-2 cell monolayer integrity when compared to the healthy controls and in the T2D patients, FW activity in vitro correlated with biological markers of T2D severity measured in vivo. Additionally, cytokines were measured in T2D faecal samples using a human cytokine array. Finally, GOS anti-cytotoxic activity was also assessed in vitro using cell viability assays and the anti-cytotoxic effect of GOS was time and concentration dependent. Together, the thesis explored potential new ways of using faecal samples as biomarker for T2D in vitro and relating it to in vivo parameters of the patients. Also future work in this area may reveal mechanistic insight to the use of FW as a non-invasive biomarker for T2D

Faecal <i>Enterobacteriales</i> enrichment is associated with increased in-vivo intestinal permeability in humans

Type 2 diabetes (T2D) has been linked with increased intestinal permeability, but the clinical significance of this phenomenon is 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, endotoxaemia 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 = 40 0.034) and plasma non-esterified fatty acid levels (P = 0.05) 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 non-diabetic controls. Therefore, enrichment in the gram- negative order Enterobacteriales may characterise impaired colonic permeability prior to/independently from a disruption in glucose tolerance

Faecal <i>Enterobacteriales</i> enrichment is associated with increased in-vivo intestinal permeability in humans

Type 2 diabetes (T2D) has been linked with increased intestinal permeability, but the clinical significance of this phenomenon is 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, endotoxaemia 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 = 40 0.034) and plasma non-esterified fatty acid levels (P = 0.05) 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 non-diabetic controls. Therefore, enrichment in the gram- negative order Enterobacteriales may characterise impaired colonic permeability prior to/independently from a disruption in glucose tolerance

Host-microbiome interactions in human type 2 diabetes following prebiotic dietary fibre (galacto-oligosaccharide) intake

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

Galacto-Oligosaccharide has no Effect on Glucose Tolerance, inflammatory Markers or Intestinal Permeability in Well-controlled Type 2 Diabetes

No abstract available