Project description:Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR.
Project description:the commensal gut microbiota modulates multiple sclerosis with unknown mechanisms. Commensal bacteria producing bile acid-deconjugating enzymes are fundamental to generate secondary bile acid metabolites (BAM) with immunoregulatory function. We show that immune regulatory BAM prevent autoimmunity in the central nervous system by inducing immune tolerance at the intestinal level and peripherally limiting effector function and aggressiveness of myelin-reactive T cells. We validated the key role of microbiota-induced BAM in humans by showing that relapsing-remitting multiple sclerosis patients have significantly reduced level of an important immune regulatory BAM (deoxycholic acid) and lower abundance of BAM-producing bacteria that correlate with increased percentages of peripheral effector Th17 cells. Our data indicate that the immune regulatory biliary network is crucial for the prevention of central nervous system autoimmunity.
2025-03-17 | GSE233771 | GEO
Project description:Human biliary microbiota
| PRJNA580086 | ENA
Project description:Explore the effect of endoscopic retrograde cholangiopancreatography on biliary microbiota and metabolite: New insights into the occurrence of recurrent choledocholithiasis
Project description:Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR
2016-02-04 | GSE77507 | GEO
Project description:gut microbiota in biliary atresia
| PRJNA880450 | ENA
Project description:Gut microbiota of biliary atresia