Project description:FLORINASH - The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD) EU FP7-HEALTH, project number 241913<br>Florinash examined the role on the gut microbiota in NAFLD. Metagenomic, proteomic, metabolomic and transcriptomic data were integrated to give provide a systems biology approach to disease-associated studies. Liver biopsies were obtained from patients undergoing bariatric surgery; one was used to diagnose NAFLD, the other was used to examine the host transcriptome in NAFLD. This dataset is part of the TransQST collection.
Project description:Bile and its individual components, mainly bile acids, are important for digestion and drive bacteria community dynamics in the upper gastrointestinal tract of chickens. However, specific responses to bile acids have been characterized in only a few commensal bacteria, and it is unclear how other members of the microbiota respond to biliary stress. Here, we used label-free LC-MS/MS to assess the proteomic response of a common inhabitant of the chicken upper intestinal tract, Turicibacter spp. MMM721, to 24 hours of growth in anaerobic growth media supplemented with 0.1% whole chicken bile, 0.1% taurochenodeoxycholic acid, or 0.1% taurocholic acid. 70, 46, and 8 differentially expressed proteins were identified in Turicibacter spp. MMM721 cultured with supplements of whole chicken bile, TCDCA, and TCA, respectively, when compared to unsupplemented controls. Many of the differentially expressed proteins were involved in ribosomal processes, post-translational modifications and chaperones, and modifications to the cell surface. To our knowledge, this work represents the first description of the Turicibacter spp. MMM721 proteomic response to bile and bile acid exposure. Ultimately, the T. bilis MMM721 response to whole bile and bile acids is highly complex, with numerous proteins from a variety of functional categories being induced.
Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA in shock experiments as well as during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection.
Project description:Liver sinusoidal endothelial cells (LSEC) are unique endothelial cell typelining the sinusoids of the liver and we have shown that these cells respond in a unique matter when exposed to saturated and unsaturated free fatty acids (FFA) and bile acids. We used microarray to analyze the transcriptional differences between the LSEC exposed to free fatty acids and bile acid receptor agonists to further shed light on their role in non-alcoholic fatty liver disease. The Murine Liver Sinusoidal Endothelial Cell Line (TSEC) was treated with palmitic and oleic acid or the bile acid receptor agonist INT-767 for 8 hours. Total RNA was then harvested to determine transcriptional differences.
Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection
Project description:Scope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
Project description:Liver sinusoidal endothelial cells (LSEC) are unique endothelial cell typelining the sinusoids of the liver and we have shown that these cells respond in a unique matter when exposed to saturated and unsaturated free fatty acids (FFA) and bile acids. We used microarray to analyze the transcriptional differences between the LSEC exposed to free fatty acids and bile acid receptor agonists to further shed light on their role in non-alcoholic fatty liver disease.