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

Abstract

ObjectiveThe 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.MethodsThe 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 gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS).ResultsDespite 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.ConclusionsThe gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.

Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation

“…As previously described, HFD-induced dysbiosis was characterized by an increase in Gram-negative bacteria and, most important, by a general decrease of total bacteria concentration [40]. In turn, it has been described that differences in gut microbial composition can determine response to HFD in mice [29,41], which would explain the wide spectrum of NAFLD observed in our study in accordance with the individual metabolic phenotype, as corroborated by results obtained from correlation analysis.…”

Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

“…Both are known to colonize the intestinal mucus and have been found in liver, in the latter case even in bile (Fox et al, 1995(Fox et al, , 2011. As a consequence of HFD-induced obesity, the abundance of phylum Deferribacteres increased in the gut microbiome, especially the abundance of the genus Mucispirillum (Ravussin et al, 2012;Serino et al, 2012). The highly abundant OTU belonging to Mucispirillum schaedleri seems to be an important factor in the metabolism of C57N mice.…”

High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

“…Taken together, these findings suggest that a fat-enriched diet is central to the loss of epithelial barrier integrity, which in turn directly or indirectly affects the microbiota, causing a dysbiosis that further alters epithelial homeostasis. Several studies have addressed the long-term effects of HF diet in such pathologies (40)(41)(42). Interestingly, most studies have characterized the fecal or cecal luminal microbiota; however, very few have attempted to characterize the mucosa-associated microbiota in the upper digestive segments, even though basic functions performed by the SI need to be tightly preserved to maintain health.…”