Project description:The intestinal microbiota has been identified as an environmental factor that markedly impacts energy storage and body fat accumulation, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells and the amplitude of the circadian oscillation is controlled by the microbiota through type 3 innate lymphoid cells (ILC3), STAT3, and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.
Project description:A study aiming to determine if mice humanized by different donors have different gut microbiota and colonic gene expression patterns in response to the administration of a commonly prescribed, broad-spectrum antibiotic (co-amoxiclav). Male, germ-free mice were humanized by one of two healthy, unrelated human donors. 56 days later, gut microbiota and colonic transcriptome samples were analyzed at baseline, by 454 pyrosequencing and Agilent microarray, respectively. Antibiotics were then administered for 7 days, following by repeated sampling of both the microbiota and colonic RNA at days 8, 11 and 18. Results of the microbiota analysis revealed marked shifts in the composition of one donor group in response to antibiotics and not the other donor group. Transcriptomics revealed a more conserved response, however the magnitude of the effect was greater in the donor group that had a greater shift in the microbiota.
Project description:The intra sub-species diversity of six strains of Lactococcus lactis subsp. lactis was investigated at the genomic level and in terms of phenotypic and transcriptomic profiles in UF-cheese model. Six strains were isolated from various sources, but all are exhibiting a dairy phenotype. Our results showed that, the six strains exhibited small phenotypic differences since similar behaviour in terms of growth was obtained during cheese ripening while only different acidification capability was detected. Even if all strains displayed high genomic similarities, sharing a high core genome of almost two thousands genes, the expression of this core genome directly in the cheese matrix revealed major strain-specific differences. This strains with the same dairy origin.
Project description:RNA-seq was used in combination with various analytical chemistry approaches to identify the chemical and genetic basis of pigment production of the bacterium Glutamicibacter arilaitensis when growing on cheese. This bacterium commonly found in cheese rinds where it co-occurs with Penicillium species and other molds. Pinkish-red pigments are produced by the bacterium in response to growth with Penicillium. Both chemical analyses and RNA-seq point to coproporphyrin III as the major metabolite leading to pigment formation.
Project description:We studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis. Keywords: Diet intervention study Nine-week-old C57Bl/6J mice were fed a low-fat diet (LF-PO) and three different types of high-fat diet, based on palm oil (HF-PO; P/S1.0), olive oil (HF-OO; P/S4.6) and safflower oil (HF-SO; P/S10.1) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. After 2 weeks of diet intervention, 6 mice per high-fat diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on mucosal scrapings.
Project description:A mucus layer covers and protects the intestinal epithelial cells from direct contact with microbes. This mucus layer not only prevents inflammation but also plays an essential role in microbiota colonization, indicating the complex interplay between mucus composition-microbiota and intestinal health. However, it is unknown whether the mucus layer is influenced by age or sex and whether this contributes to reported differences in intestinal diseases in males and females or with ageing. Therefore, in this study we investigated the effect of age on mucus thickness, intestinal microbiota composition and immune composition in relation to sex. The ageing induced shrinkage of the colonic mucus layer was associated with bacterial penetration and direct contact of bacteria with the epithelium in both sexes. Additionally, several genes involved in the biosynthesis of mucus were downregulated in old mice, especially in males, and this was accompanied by a decrease in abundances of various Lactobacillus species and unclassified Clostridiales type IV and XIV and increase in abundance of the potential pathobiont Bacteroides vulgatus. The changes in mucus and microbiota in old mice were associated with enhanced activation of the immune system as illustrated by a higher percentage of effector T cells in old mice. Our data contribute to a better understanding of the interplay between mucus-microbiota-and immune responses and ultimately may lead to more tailored design of strategies to modulate mucus production in targeted groups.
Project description:The goal of this project was to use a randomized, cross over design to determine the amino acid blood and muscle response to the acute ingestion of cheddar cheese in comparison to that of bovine milk and to investigate the skeletal muscle mTORC1 response.