Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gut microbiota-induced perturbations in bile acids alter keratinocyte lipid metabolism via FXR-NQO1 signaling in psoriasis

ABSTRACT: Emerging evidence has shown that microbiota dysbiosis and aberrant bile acids (BAs) profiles are correlated with disease progression. This study elucidates dysregulated BAs metabolism in psoriasis patients and imiquimod-treated female mice, coupled with increased expression of the farnesoid X receptor (FXR) in keratinocytes. Activation of FXR by glycochenodeoxycholic acid (GCDCA) ameliorates psoriatic symptoms by enhancing lipid metabolism, particularly fatty acid oxidation. Mechanistically, the FXR-mediated enhancement of antioxidant capacity by upregulating NAD(P)H quinone dehydrogenase 1 (NQO1) expression underlies its regulatory role in lipid metabolism, offering an insight into FXR’s role in oxidative stress and lipid metabolism. Conversely, keratinocyte-specific FXR ablation exacerbates psoriasis severity. Gut microbiota dysbiosis is further identified as a pivotal contributor to perturbations in BA profiles in psoriasis. These findings support a mechanistic model linking gut microbiota and BA alterations to FXR signaling in keratinocytes and psoriasis-associated metabolic dysregulation, suggesting therapeutic potential for microbiota-targeted interventions.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse-phase

PROVIDER: MTBLS14183 | MetaboLights | 2026-03-29

REPOSITORIES: MetaboLights

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	a_MTBLS14183_LC-MS_alternating_reverse-phase.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS14183_LC-MS_alternating_reverse-phase_v2_maf.tsv	Tabular
	s_MTBLS14183.txt	Txt

Items per page:

1 - 4 of 4

Similar Datasets

Gut microbiota-induced perturbations in bile acids alter keratinocyte lipid metabolism via FXR-NQO1 signaling in psoriasis

Project description:Emerging evidence has shown that microbiota dysbiosis and aberrant bile acids (BAs) profiles are correlated with disease progression. This study elucidates dysregulated BAs metabolism in psoriasis patients and imiquimod-treated female mice, coupled with increased expression of the farnesoid X receptor (FXR) in keratinocytes. Activation of FXR by glycochenodeoxycholic acid (GCDCA) ameliorates psoriatic symptoms by enhancing lipid metabolism, particularly fatty acid oxidation. Mechanistically, the arrow_drop_downmore

2026-03-31 | MTBLS14191 | MetaboLights

Altered mRNA expression profile of GW4064 treated mouse livers compared to vehicle control

2014-07-24 | GSE57305 | GEO

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 mRNA expression profile of GW4064 treated mouse livers compared to vehicle control

Project description:Farnesoid X receptor (FXR) is a ligand activated nuclear receptor belonging to the nuclear receptor superfamily. Bile acids (BAs) are the endogenous ligand for FXR. FXR is a master regulator of BA homestasis, including BA synthesis, metabolism, transport, and enterohepatic circulation of BAs. Besides, FXR is involved in regulating diverse physioligical function in both humans and mice. GW4064 is a synthetic FXR agonist which selectively activates FXR and induce the transcription of FXR target genes. In this study, we treated wild type C57BL/6J mice with GW4064 at 100mg per kg body weight or vehicle control. Mice were treated three times, first dose at 8 am, second dose at 6 pm, third dose at 8 am the second day. Mice were sacrificed 2 hours after the last dose, and liver tissues were harvested for analysis. Animal protocols and procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Kansas Medical Center. Total RNA from livers was prepared with TRIzol Reagent (Invitrogen, CA), and the whole transcription expression levels were determined using Mouse Gene 1.0 ST Array system manufactured by Affymetrix, Inc..

2014-07-24 | E-GEOD-57305 | biostudies-arrayexpress

Prevention of cholestatic liver disease through BCL6-FXR enterohepatic crosstalk [ChIP-seq]

Project description:Bile acid (BA) metabolism must be tightly regulated because BAs serve as metabolic signaling molecules but become cytotoxic at high levels. The farnesoid X receptor (FXR) is a crucial bile acid sensor, but our understanding of its regulation and coordination with other transcription factors is limited. Here, we found that B cell lymphoma 6 (Bcl6) functions along with FXR to control bile acid levels. We found that mice lacking hepatic BCL6 (Bcl6LKO) had increased BA synthesis and serum levels. In line with this, Bcl6LKO mice had elevated serum cholesterol, the upstream substrate for BA synthesis, as well as reduced expression of the hepatic BA re-uptake transporter sodium-taurocholate cotransporting polypeptide (NTCP). Furthermore, loss of BCL6 reduced hepatic fibroblast growth factor 4 (FGFR4) expression, causing dysregulated entero-hepatic BA feedback signaling. To better understand the relative contribution of BCL6 and FXR in regulating BA homeostasis, we generated mice with a combined deletion of hepatic BCL6 and FXR (Bcl6LKOFxrKO). Critically, combined deletion of FXR and hepatic BCL6 caused massive elevations in BA synthesis/levels compared to loss of Fxr or Bcl6 alone, which resulted in cholestatic liver damage. Mechanistically, we found that Bcl6LKO FxrKO mice had an almost complete loss of hepatic Shp expression, causing high levels of the rate-limiting BA synthesis enzyme CYP7A1. Together, these findings demonstrate that BCL6 and FXR function together to limit BA synthesis and protect the liver from cholestatic injury.

2026-02-11 | GSE290307 | GEO

Prevention of cholestatic liver disease through BCL6-FXR enterohepatic crosstalk

2026-02-11 | GSE296552 | GEO

Prevention of cholestatic liver disease through BCL6-FXR enterohepatic crosstalk [RNA-seq]

2026-02-11 | GSE290309 | GEO

Gene expression analysis of FXR null, SHP null, and double FXR/SHP null mice

Project description:Bile acid (BA) homeostasis is maintained through a feedback loop operated by the nuclear hormone receptors FXR and SHP. Here we show that contrary to the current models placing FXR upstream of SHP in a linear regulatory pathway, the phenotypic consequence of the combined loss of both receptors is much more severe than the relatively modest impact of the loss of either Fxr or Shp alone. This is highlighted by the dramatic elevation of hepatic and serum BA levels in the double knockout (DKO) mice as early as three weeks of age coupled with a commensurate increase in Cyp7A1 expression and alterations in BA homeostatic genes. In addition, we find several genes necessary for C21 steroid biosynthetic pathway as novel targets for FXR and SHP. The elevated BAs result in severe hepato-pathology but the DKO mice surprisingly do not develop complete liver failure and live for over a year. Their survival is accompanied by an adaptive proliferation of the resident liver progenitor cell population, known as oval cells. Overall, these data demonstrate that FXR and SHP function coordinately to maintain BA homeostasis, and identify DKO mice as a novel genetic model for juvenile cholestatic disorders and for oval cell activation. Liver samples collected from FXR-/-, SHP-/-, and FXR-/-/SHP-/- animals at 3 or 5 weeks were hybridized to Illumina mouse REF-8 v1.1 arrays in duplicate.

2010-12-10 | E-GEOD-20599 | biostudies-arrayexpress

Activation of FXR by bile acids in hepatic stellate cells plays a critical role in liver cirrhosis

Project description:Cirrhosis is a late stage of fibrosis impairing liver function. Genetic animal models for cirrhosis are lacking, and molecular mechanisms remain unknown. We report the first murine genetic model recapitulating human cirrhosis induced by hepatocyte-specific elimination of MCRS1, a member of NSL and INO80 chromatin-modifier complexes. MCRS1 loss in hepatocytes modulates the expression of bile acid (BA) transporters, with a pronounced NTCP downregulation, concentrating BAs in liver sinusoids, thereby activating hepatic stellate cell (HSC) via FXR. Consistently, genetic FXR ablation in HSCs suppresses fibrotic marks in mice and in vitro cell culture. Mechanistically, deletion of a putative SANT domain from MCRS1 evicts HDAC1 from its H3 anchoring sites, increasing histone acetylation of BA transporter genes, modulating their expression and perturbing BA flow. Accordingly, human cirrhosis displays loss of nuclear MCRS1 and decreased NTCP expression. Thus, histone acetylation-mediated dysregulation of BA transporters, and consequently FXR activation by BAs in HSCs represent a central and universal signaling event in cirrhosis. The data is from single-nuclei RNA-seq of whole-liver collected during autopsy of 4 individuals with COVID-19 and PMI < 4.5 hours

2023-07-03 | GSE179548 | GEO

An FXR-Casp6 axis-mediated bile acid/gut microbiota sensing modulates neonatal β-cell mass expansion [scATAC-Seq]

Project description:Weaning diet switch brings gut microbiome maturation along with postnatal formation of sufficient matured β-cell mass. The matured gut microbiota elevated agonistic components of bile acid (BA) pool towards farnesoid X receptor (FXR) that was paralleling with the declined β-cell FXR expression. To investigate whether BA/FXR could link postnatal β-cell development and gut microbiota maturation, we forced persistent FXR expression in β cells (βFxrKI) and found decreased neonatal β-cell mass growth and increased glycemia in weaned βFxrKI mice, which could be partially recovered by ablating gut microbiota before weaning. scRNA and scATAC seq analysis showed different β cell growth trajectories with suppressed intrinsic cell proliferation and elevated cell apoptosis in βFxrKI. Caspase-6 was then identified as a dominant β-cell FXR downstream effector to mediate its regulation. The negative regulation of the FXR-Casp6 axis on postnatal β-cell mass expansion reflected a programmed cellular response to gut microbiota maturation in neonatal mice.

2025-11-13 | GSE241406 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data