ER body and indole glucosinolate modulaing microbiota assembly
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ABSTRACT:
PROVIDER: PRJEB54088 | ENA |
REPOSITORIES: ENA
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Project description:The microbiota generates diverse metabolites to modulate host physiology and disease, but their protein targets and mechanisms of action have not been fully elucidated. To address this challenge, we focused on microbiota-derived indole metabolites and develop photoaffinity chemical probes for proteomic studies. We identified many potential indoleinteracting proteins, including metabolic enzymes, transporters, immune sensors, and Gprotein coupled receptors. Notably, we discovered aromatic monoamines can activate - arrestin recruitment by the orphan receptor GPRC5A. Metabolomic and functional profiling of microbiota species revealed specific aromatic amino acid decarboxylaseexpressing bacteria producing monoamine agonists for GPRC5A. Structure-activity relationship studies of synthetic aromatic monoamines identified 7-fluorotryptamine as a more potent activator of -arrestin recruitment by GPRC5A. Our results highlight the utility of chemoproteomics to identify novel microbiota metabolite-interacting proteins and discover potential microbiota-derived small molecule agonists for orphan receptors.
2023-05-31 | PXD040163 | Pride
Project description:RNA seq experiment was perfomed in the presence and absence of 500uM indole
2019-01-05 | GSE119440 | GEO
Project description:The intestinal microbiota has been identified as an environmental factor that markedly impacts energy storage and body fat accumulation, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells and the amplitude of the circadian oscillation is controlled by the microbiota through type 3 innate lymphoid cells (ILC3), STAT3, and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.
2017-09-26 | GSE100339 | GEO
Project description:Indole signaling at the host-microbiota-pathogen interface
| PRJNA489260 | ENA
Project description:Altered tryptophan catabolism has been identified in inflammatory diseases like rheumatoid arthritis (RA) and spondyloarthritis (SpA), but the causal mechanisms linking tryptophan metabolites to disease are unknown. Using the collagen-induced arthritis (CIA) model we identify alterations in tryptophan metabolism, and specifically indole, that correlate with disease. We demonstrate that both bacteria and dietary tryptophan are required for disease, and indole supplementation is sufficient to induce disease in their absence. When mice with CIA on a low-tryptophan diet were supplemented with indole, we observed significant increases in serum IL-6, TNF, and IL-1β; splenic RORγt+CD4+ T cells and ex vivo collagen-stimulated IL-17 production; and a pattern of anti-collagen antibody isotype switching and glycosylation that corresponded with increased complement fixation. IL-23 neutralization reduced disease severity in indole-induced CIA. Finally, exposure of human colon lymphocytes to indole increased expression of genes involved in IL-17 signaling and plasma cell activation. Altogether, we propose a mechanism by which intestinal dysbiosis during inflammatory arthritis results in altered tryptophan catabolism, leading to indole stimulation of arthritis development. Blockade of indole generation may present a novel therapeutic pathway for RA and SpA.
2023-11-13 | GSE241655 | GEO
Project description:Root exudates are composed of primary and secondary metabolites known to modulate the rhizosphere microbiota. Glucosinolates are defense compounds present in the Brassicaceae family capable of deterring pathogens, herbivores and biotic stressors in the phyllosphere. In addition, traces of glucosinolates and their hydrolyzed byproducts have been found in the soil, suggesting that these secondary metabolites could play a role in the modulation and establishment of the rhizosphere microbial community associated with this family. We used Arabidopsis thaliana mutant lines with disruptions in the indole glucosinolate pathway, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and 16S rRNA amplicon sequencing to evaluate how disrupting this pathway affects the root exudate profile of Arabidopsis thaliana, and in turn, impacts the rhizosphere microbial community. Chemical analysis of the root exudates from the wild type Columbia (Col-0), a mutant plant line overexpressing the MYB transcription factor ATR1 (atr1D) which increases glucosinolate production, and the loss-of-function cyp79B2cyp79B3 double mutant line with low levels of glucosinolates confirmed that alterations to the indole glucosinolate biosynthetic pathway shifts the root exudate profile of the plant. We observed changes in the relative abundance of exuded metabolites. Moreover, 16S rRNA amplicon sequencing results provided evidence that the rhizobacterial communities associated with the plant lines used were directly impacted in diversity and community composition. This work provides further information on the involvement of secondary metabolites and their role in modulating the rhizobacterial community. Root metabolites dictate the presence of different bacterial species, including plant growth-promoting rhizobacteria. Our results suggest that alterations in the indole glucosinolate pathway cause disruptions beyond the endogenous levels of the plant, significantly changing the abundance and presence of different metabolites in the root exudates of the plants as well as the microbial rhizosphere community.
2023-05-31 | MSV000092068 | MassIVE
Project description:Purpose: The goal of this study was to identify transcriptional changes in HCT-8 cells treated with indole for 4 or 12 hours. Methods: Confluent HCT-8 monolayers were infected with excysted Cryptosporidium parvum sporozoites for 4 h, after which cells were washed to remove extracellular parasites. Cells were then treated with 1% DMSO in cell culture medium with or without 880 uM indole. RNA was collected in triplicate for each treatment type after 4 h and 12 h of treatment (8 and 16 hours post infection, respectively). Results: When the two time points were combined, indole significantly upregulated 57 genes and downregulated 11 genes. Of the upregulated genes,16 genes were primarily upregulated in cells exposed to indole for 4 h and then went back down by 12 h of exposure. These genes were primarily involved in pathways related to ER stress and the unfolded protein response (UPR). Conversely, 41 genes had higher gene expression after 12 h of indole exposure and were predominantly involved in membrane transport of carboxylic acids and amino acids. Conclusions: Indole treatment causes ER stress and upregulation of membrane transporters in a human adenocarcinoma cell line infected with Cryptosporidium parvum.
2021-10-13 | GSE185652 | GEO
Project description:Indole-3-carbinol (I3C) is a natural anti-carcinogenic compound found at high concentrations in Brassica vegetables. ER-positive cell lines demonstrated the greatest sensitivity to the anti-tumor effects of I3C compared to ER-negative breast cancer cell lines. Gene expression analysis was performed to identify genes and pathways that accounted for sensitivity to I3C. Microarray analysis performed using Illumina HT-12 v4 expression arrays
2014-08-12 | GSE55897 | GEO
Project description:Indole-3-pyruvate (I3P), an endogenous metabolite derived from tryptophan by gut microbiota and IL4I1 enzyme in humans can potentially activate the transcriptional activity of the Aryl Hydrocarbon receptor. Here we test this by stimulating AHR proficient U-87MG cells with I3P alone or in combination with the AHR antagonist SR1.
2020-08-19 | GSE143240 | GEO