Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.RegIIIγ | LPS | gut permeability | Lactobacillus plantarum | antimicrobial peptides G ut microbiota were once characterized as bystanders in the intestinal tract, but their active role in intestinal physiology is now widely investigated. In particular, the mutualism that exists between gut microbiota and the host has received much attention. Obesity and type 2 diabetes are characterized by altered gut microbiota (1), inflammation (2), and gut barrier disruption (3-5). We recently demonstrated an association of obesity and type 2 diabetes with increased gut permeability, which induced metabolic endotoxemia and metabolic inflammation (3-5). Unequivocal evidence demonstrates that gut microbiota influence whole-body metabolism (1, 6) by affecting the energy balance (6), gut permeability (4, 5), serum lipopolysaccharides [i.e., metabolic endotoxemia (7)], and metabolic inflammation (3-5, 7) that are associated with obesity and associated disorders. However, the microbial composition and the exact mechanisms of interaction between these two partners that affect host-gut barrier function and metabolism remain unclear.The intestinal epithelium is the interface for the interaction between gut microbiota and host tissues (8). This barrier is enhanced by the presence of a mucus layer an...

We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities

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The diversity of mucin-degrading bacteria in the human intestine was investigated by combining culture and 16S rRNA-dependent approaches. A dominant bacterium, strain Muc T , was isolated by dilution to extinction of faeces in anaerobic medium containing gastric mucin as the sole carbon and nitrogen source. A pure culture was obtained using the anaerobic soft agar technique. Strain Muc T was a Gram-negative, strictly anaerobic, non-motile, non-spore-forming, oval-shaped bacterium that could grow singly and in pairs. When grown on mucin medium, cells produced a capsule and were found to aggregate. Strain Muc T could grow on a limited number of sugars, including N-acetylglucosamine, N-acetylgalactosamine and glucose, but only when a protein source was provided and with a lower growth rate and final density than on mucin. The G+C content of DNA from strain Muc T was 47?6 mol%. 16S rRNA gene sequence analysis revealed that the isolate was part of the division Verrucomicrobia. The closest described relative of strain Muc T was Verrucomicrobium spinosum (92 % sequence similarity). Remarkably, the 16S rRNA gene sequence of strain Muc T showed 99 % similarity to three uncultured colonic bacteria.

OBJECTIVETo investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice.RESEARCH DESIGN AND METHODSGenetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.RESULTSIn ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat–fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters.CONCLUSIONSWe conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.