Project description:Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. In a healthy physiological state of the gut (eubiosis), E. faecalis is a subdominant species in the intestinal microbiota. When the intestinal homeostasis is disrupted (dysbiosis), it becomes dominant species and can cause infections. The taurocholate bile acid (TCA) becomes prominent during dysbiosis. This experiment aimed to better understand how E. faecalis adapts to TCA. We showed that TCA reprograms genes involved in the pool management of amino acids and nucleotides.
Project description:bsh-expressing E. coli cultured with bile acids (TCA, TDCA, TLCA) and drug for 48 h. Samples were run on a Kinetex (Phenomenex) polar C18 column (100 x 2.1 mm, 2.6 um 100A).
Project description:Intestinal lipid absorption, the entry point for fats into the body, requires the coordinated actions of bile acids and lipases. Here, we uncover distinct yet cooperative roles of bile acids in driving the differential uptake of dietary fatty acids. We first decreased the bile acid pool size by disrupting the rate-limiting enzyme in bile acid synthesis, Cyp7a1, using liver-directed gene editing in mice. Compared with lipase inhibition, reduced bile acids prevented diet-induced obesity, increased anorectic hormones, suppressed excessive eating, and improved systemic lipid metabolism. Remarkably, decreasing bile acids selectively reduced the absorption of saturated fatty acids but preserved polyunsaturated fatty acids. By targeting additional bile acid enzymes, we identified specific functions of individual bile acid species. Mechanistically, we show that cholic acid preferentially solubilizes polyunsaturated fatty acids into mixed micelles for intestinal uptake. Our studies demonstrate that bile acids can selectively control fatty acid uptake, revealing insights for future interventions in metabolic diseases.
Project description:Tumor organoids of a patient with microsatellite stable (MSS) colorectal cancer were co-incubated with primary bile acids (CA, GCA, TCA; 100 µM) to analyze the effect of bile acids on tumorigenesis of colorectal cancer.
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:Cholestasis is caused by autoimmune reactions, drug-induced hepatotoxicity, viral infections of the liver and the obstruction of bile ducts by tumours or gallstones. Cholestatic conditions are associated with impaired innate and adaptive immunity, including alterations of the cellular functions of monocytes, macrophages, NK cells and T-cells. Bile acids act as signalling molecules, affecting lipopolysaccharide (LPS)-induced cytokine expression in primary human macrophages. The present manuscript investigates the impact of bile acids, such as taurolithocholic acid (TLC), on the transcriptome of human macrophages in the presence or absence of LPS. While TLC itself has almost no effect on gene expression under control conditions, this compound modulates the expression of 202 out of 865 transcripts in the presence of LPS. Interestingly, pathway analysis revealed that TLC specifically supressed the expression of genes involved in mediating pro-inflammatory effects, phagocytosis, interactions with pathogens and autophagy as well as the recruitment of immune cells, such as NK cells, neutrophils and T cells. These data indicate a broad influence of bile acids on inflammatory responses and immune functions in macrophages. These findings may contribute to the clinical observation that patients with cholestasis present a lack of response to bacterial or viral infections.