Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota

Objective The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. Methods The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a glucooligosaccharide (GOS)-supplemented HFD (HFD+GOS). Results Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. Conclusions The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet

In vitro screening of probiotics and synbiotics according to anti-inflammatory and anti-proliferative effects

International audienceThere is emerging evidence of the efficiency of probiotic, prebiotic and synbiotic treatments in inflammatory bowel diseases (IBDs) and one of their long-term complications, colorectal cancer (CRC). In this study, various strains of probiotic lactic acid bacteria, prebiotic glucooligosaccharides (GOS) or a synbiotic combination of the two were screened for anti-inflammatory and anti-proliferative effects in different in vitro models in the context of such diseases. To mimic IBD response to Gram negative bacteria, HT-29 cells were sensitised to inflammatory response to lipopolysaccharide (LPS) by IFN gamma which increased expression of TLR4, the LPS biosensor, and were then treated by probiotics, prebiotics and synbiotics. Secreted IL-8 and activated NF-kappa B were monitored as inflammation biomarkers. A selection of active strains were then subjected to a second inflammatory cell culture model consisting of inflammatory activated transgenic Caco-2 cells transfected by a reporter gene under the control of NF-kappa B inducible promoter. Quantification of reporter gene expression allowed us to demonstrate some probiotic inhibitory properties or to confirm such characteristics in two different models. Proliferation of cancerous HT-29 cells was monitored by XTT assay. Only three probiotic strains induced a proliferation decrease, but with a lack of reproducibility. Binary or ternary probiotic associations, complemented or not by prebiotic GOS, significantly decreased proliferation, especially with a synbiotic association of Bifidobacterium breve, Lactococcus lactis and oligoalternan. a GOS. This combination was selected for the following experiments. We showed the involvement of both bacterial and carbohydrate compounds of this synbiotic in the observed effect by dose range tests. We demonstrated that this decrease in proliferation may be due to an induction of a differentiated phenotype, as shown by the up-regulation of intestinal alkaline phosphatase, a biomarker of differentiation, monitored by real-time RT-PCR in HT-29 cells treated by the selected synbiotics. Thus, this study demonstrates the ability of probiotics to exert anti-inflammatory effects and shows some anti-proliferative characteristics for a specific synbiotics. These products should be further evaluated in animal models to confirm the in vitro results. (C) 2010 Elsevier B.V. All rights reserved