Similar Datasets
Project description:Gut dysbiosis compromises cancer immunosurveillance by downregulating ileal mucosal addressin cell adhesion molecule 1 (MAdCAM-1) but the metabolic landscape associated with gut dysbiosis remains elusive. Here, we show that antibiotics (ABX) or ABX-associated Enterocloster species, lead to the loss of secondary cholic acid-derived bile acids, BA (DCA) and the accumulation of tauro-conjugated primary BA (TCDCA, T-abo-MCA) in the plasma of patients and mice. DCA/GDCA (glyco-DCA) compensated dysbiosis bile acid abnormalities and circumvented primary resistance to PD-1 blockade. GDCA curtailed ABX-induced MAdCAM-1 downregulation and seemed to have an impact on anti tumor immunity. The single cell RNA sequencing in a mouse model of MCA205 fibrosarcoma helped us to characterize the effect of GDCA or DCA on anti tumor immunity and showed a decrease in T cell exhaustion in the TME.
2026-06-23 | GSE326943 | GEO
Project description:Metabolic products of the microbiota can alter hematopoiesis. However, the contribution and site of action of bile acids is poorly understood. Here we demonstrate that the secondary bile acids, deoxycholic acid (DCA), and lithocholic acid (LCA) increase bone marrow myelopoiesis. Treatment of bone marrow cells with DCA and LCA preferentially expanded immunophenotypic and functional (CFU-GM) granulocyte-monocyte progenitors (GMPs). DCA treatment of sorted hematopoietic stem/progenitor cells (HSPCs) increased CFU-GMs, indicating that direct exposure of HSPCs to DCA sufficed to expand GMPs. We determined that the vitamin D receptor (VDR) was required for the DCA-induced increase in CFU-GMs and GMPs. Finally, single-cell RNA sequencing revealed that DCA significantly upregulated genes associated with myeloid differentiation and proliferation in GMPs. The action of DCA on HSPCs to expand GMPs in a VDR-dependent manner suggests a mechanism for how microbiome-host interactions may directly impact bone marrow hematopoiesis and the severity of infectious and inflammatory disease.
2023-07-01 | GSE215639 | GEO
Project description:The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD) patients. The vermiform appendix is a lymphoid tissue implicated in the storage and regulation of the gut microbiome. Here, we investigate changes in the functional microbiome in the appendix of PD patients relative to controls by metatranscriptomic analysis. In the PD appendix, we find microbial dysbiosis affecting lipid metabolism, particularly an upregulation of bacteria responsible for secondary bile acid synthesis. Likewise, proteomic and transcript analysis in the PD gut corroborates a disruption in cholesterol homeostasis and lipid catabolism. Bile acid analysis in the PD appendix reveals an increase in the microbially-derived, toxic secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA). Synucleinopathy in mice induces similar microbiome alterations to those of PD patients and heightens microbial changes to gut inflammation. As observed in PD, the mouse model of synucleinopathy has elevated DCA and LCA. Raised levels of DCA and LCA can lead to liver injury, and an analysis of blood markers of liver dysfunction shows evidence of biliary abnormalities in PD patients, including elevated alkaline phosphatase and bilirubin. Increased bilirubin levels are also evident before PD diagnosis, in individuals at-risk of developing PD. In sum, microbially-derived toxic bile acids are heightened in PD and biliary changes may even precede the onset of overt motor symptoms.
2021-01-28 | PXD020988 | Pride
Project description:The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD) patients. The vermiform appendix is a lymphoid tissue implicated in the storage and regulation of the gut microbiome. Here, we investigate changes in the functional microbiome in the appendix of PD patients relative to controls by metatranscriptomic analysis. In the PD appendix, we find microbial dysbiosis affecting lipid metabolism, particularly an upregulation of bacteria responsible for secondary bile acid synthesis. Likewise, proteomic and transcript analysis in the PD gut corroborates a disruption in cholesterol homeostasis and lipid catabolism. Bile acid analysis in the PD appendix reveals an increase in the microbially-derived, toxic secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA). Synucleinopathy in mice induces similar microbiome alterations to those of PD patients and heightens microbial changes to gut inflammation. As observed in PD, the mouse model of synucleinopathy has elevated DCA and LCA. Raised levels of DCA and LCA can lead to liver injury, and an analysis of blood markers of liver dysfunction shows evidence of biliary abnormalities in PD patients, including elevated alkaline phosphatase and bilirubin. Increased bilirubin levels are also evident before PD diagnosis, in individuals at-risk of developing PD. In sum, microbially-derived toxic bile acids are heightened in PD and biliary changes may even precede the onset of overt motor symptoms.
2021-08-01 | GSE156647 | GEO
Project description:Effect of bile acids (TCA LCA TUDCA DCA) on isolated bacteria
Ruminococcus bromii, Bacteroides fragilis, and Lactobacillus paracasei
2022-07-29 | MSV000090024 | GNPS
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
2019-02-09 | PXD010525 | Pride
Project description:iPOND Mass spectrometry (iPOND-MS) was performed to identify replication fork proteome in wild type (WT) and ABARAXAS KO (ABX KO) HEK293T cells treated with 1 µM CPT in combination with 250 nM ATM inhibitor (AZD0156). An additional set of control cells were kept for no-click (NC) negative control. The experiment was done with 5 repeats and the samples were designated as: WT/1, WT/2, WT/3, WT/4, WT/5, ABX KO/1, ABX KO/2, ABX KO/3, ABX KO/4, ABX KO/5, NC/1, NC/2, NC/3, NC/4, NC/5.
2026-06-15 | PXD077767 | Pride
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.
2019-02-12 | PXD010514 | Pride
Project description:Comparsion of gene expression in scWAT/pgVAT of Ctrl, ABX and SZ-ABX mice.
2018-11-01 | GSE117843 | GEO