Project description:Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is unknown. We investigated the effect of dietary lipid composition on human microbiota in an observational study and combined diet experiments with microbiota transplants to study lipid-microbiota interactions and liver status in mice. In humans, low intake of saturated fatty acids (SFA) was associated with increased microbial diversity independent of fiber intake. In mice, cecum levels of SFA correlated negatively with microbial diversity and were associated with a shift in butyrate and propionate producers. Mice fed poorly absorbed SFA had improved metabolism and liver status. These features were transmitted by microbial transfer. Diets enriched in n-6- and/or n-3-polyunsaturated fatty acids were protective against steatosis but had minor influence on the microbiota. In summary, we find that unabsorbed SFA correlate with microbiota features that may be targeted to decrease liver steatosis.
Project description:We have previously demonstrated that the gut microbiota can play a role in the pathogenesis of conditions associated with exposure to environmental pollutants. It is well accepted that diets high in fermentable fibers such as inulin can beneficially modulate the gut microbiota and lessen the severity of pro-inflammatory diseases. Therefore, we aimed to test the hypothesis that hyperlipidemic mice fed a diet enriched with inulin would be protected from the pro-inflammatory toxic effects of PCB 126.
Project description:Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism. Mice were infused in cecum with stably-labelled isotopes of the three main short chain fatty acids or control solution. After 6 hrs, livers were removed and pooled RNA samples were subjected to gene expression profiling.
Project description:The mouse stool samples were collected from different diets fed mice and bacterial cells were harvest for metaproteomic analysis for understanding the role ofdiet on gut microbiota.