Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microbial Bile Acid Metabolism Shapes Effector T Cell Responses During Inflammation in Mouse and Human

ABSTRACT: Microbial Bile Acid Metabolism Shapes Effector T Cell Responses During Inflammation in Mouse and Human

PROVIDER: PRJNA903184 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR22335649_1.fastq.gz	Fastqsanger.gz
	SRR22335649_2.fastq.gz	Fastqsanger.gz
	SRR22335650_1.fastq.gz	Fastqsanger.gz
	SRR22335650_2.fastq.gz	Fastqsanger.gz
	SRR22335651_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

Microbial Bile Acid Metabolism Shapes T Cell Responses During Inflammation

Project description:Microbial transformation of bile acids (BAs) affects intestinal immune homeostasis but the impact of changes in BA metabolism on T cell-driven pathologies remains largely unknown. Using a mouse model of graft-versus-host disease (GVHD), we found that GVHD decreased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and reduced the levels of microbiota-dependent unconjugated and secondary BAs (SBAs). Several SBAs attenuated farnesoid X receptor (FXR) activity, posing that loss of SBAs may increase FXR activation and exacerbate inflammation. Mortality in GVHD mice increased with pharmacological activation of FXR and decreased with its genetic ablation in donor T cells. Furthermore, patients with GVHD after allogeneic hematopoietic cell transplantation showed similar loss of BSH and the associated reduction in unconjugated and SBAs. Moreover, the FXR antagonist ursodeoxycholic acid reduced the activation of human T cells and was associated with a reduced risk of GVHD-related mortality in patients. We propose that dysbiosis and loss of SBAs may be an important mechanism to amplify T cell-mediated diseases.

2023-06-28 | MSV000092300 | MassIVE

Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during graft-versus-host disease

Project description:Microbial transformation of bile acids affects intestinal immune homeostasis but its impact on inflammatory pathologies remains largely unknown. Using a mouse model of graft-versus-host disease (GVHD), we found that T cell-driven inflammation decreased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and reduced the levels of unconjugated and microbe-derived bile acids. Several microbe-derived bile acids attenuated farnesoid X receptor (FXR) activation, suggesting that loss of these metabolites during inflammation may increase FXR activity and exacerbate the course of disease. Indeed, mortality increased with pharmacological activation of FXR and decreased with its genetic ablation in donor T cells during mouse GVHD. Furthermore, patients with GVHD after allogeneic hematopoietic cell transplantation showed similar loss of BSH and the associated reduction in unconjugated and microbe-derived bile acids. Additionally, the FXR antagonist ursodeoxycholic acid reduced the proliferation of human T cells and was associated with a lower risk of GVHD-related mortality in patients. We propose that dysbiosis and loss of microbe-derived bile acids during inflammation may be an important mechanism to amplify T cell-mediated diseases.

2024-02-09 | GSE253360 | GEO

Microbial Bile Acid Metabolism Shapes Effector T Cell Responses During Inflammation in Mouse and Human

Project description:To comprehensively investigate the effects of graft-versus-host disease on host metabolism, we carried out RNA-sequencing analysis of bulk liver and epithelial cell fractions of the small and large intestines of bone marrow of mice who received bone marrow (BM) only grafts and mice co-transferred with donor T cells (BMT).

2023-09-21 | GSE218343 | GEO

GNPS - Microbial Bile Acid Metabolism Shapes T Cell Responses During Inflammation

2023-06-28 | MSV000092300 | GNPS

Diet Modulation of Bacterial Sulfur and Bile Acid Metabolism and Colon Cancer Risk

Project description:Determine in the context of a controlled crossover diet-intervention trial the role of taurocholic acid metabolism by gut bacteria in African American subjects at elevated risk for colorectal cancer (CRC). Two isocaloric diets, an animal-based diet high in taurine and saturated fat (HT-HSAT) and a plant-based, low in taurine and low saturated fat (LT-LSAT) will be used to determine the extent to which the relationship between diet (independent variable) and mucosal markers of CRC risk including epithelial proliferation, oxidative stress, DNA damage, and primary and secondary bile acid pools and biomarkers of inflammation (dependent variables) is explained by the abundance of sulfidogenic bacteria and hydrogen sulfide (H2S) concentrations &/or deoxycholic acid (DCA) and DCA-producing bacteria clostridium scindens (mediator variables).

| 2274903 | ecrin-mdr-crc

MAFG is a transcriptional repressor of bile acid synthesis and metabolism (ChIP-seq)

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 | GSE77529 | GEO

Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during graft-versus-host disease

Project description:Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during graft-versus-host disease

| PRJNA1065397 | ENA

Insulin controls hepatic bile acid metabolism by the spatial repatterning of gene expression

Project description:Insulin regulation of hepatic gene expression is critical for controlling metabolism and preventing diabetes, atherosclerosis and NAFLD; yet, how insulin regulates gene expression in the spatial context of the liver lobule is largely unexplored. Here, we find that insulin regulates bile acid metabolism by segregating CYP8B1, the enzyme that catalyzes the 12α-hydroxylation of bile acids, from the other enzymes required for bile acid synthesis. When insulin signaling is disrupted, Cyp8b1 and the other bile acid synthesis genes become co-localized within the same zone, and 12α-hydroxylated bile acids, which drive atherosclerosis and NAFLD, are increased. Novel zone-specific genetic manipulations of Cyp8b1 that mimic the effects of insulin result in a more benign bile salt profile. Mechanistically, the zonal effects of insulin are not due to gradients of insulin concentration or signaling, but through insulin crosstalk with positional Wnt signals: Wnt and insulin act together to determine the complement of transcription factors active in the pericentral hepatocytes and thereby regulate Cyp8b1 zonation. Taken together, these data show that by repatterning gene expression in the liver lobule, insulin can transcriptionally regulate the outputs of a metabolic pathway. The spatial dimension of transcriptional regulation represents a novel lens with which to view the control of metabolism that may ultimately lead us to more precise therapies.

2024-09-01 | GSE242823 | GEO

MicroRNA-185 modulates CYP7A1 mediated bile acid metabolism through posttranscriptionally and posttranslationally regulation of FoxO1

Project description:Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate limiting enzyme of bile acid biosynthetic pathway to convert cholesterol to bile acids, which is a major output pathway for cholesterol catabolism. In this study, we aimed to assess the potential regulatory mechanisms of microRNA-185 (miR-185) involved in cholesterol and bile acid homeostasis. This study provides convincing evidences about the critical role of miR-185 in FoxO1 modulation at both posttranscriptional and posttranslational levels, which account for the effects on CYP7A1 gene and its mediated cholesterol-bile acid metabolism. These results suggest an important role of miR-185 as a novel atherosclerosis-protective target for drug discovery.

2023-03-26 | GSE169693 | GEO

Bile acid therapeutics for NASH

Project description:Bile acid therapeutics for NASH

| PRJNA705980 | ENA