scholarly journals POS-431 ALTERED REGULATION OF TRYPTOPHAN METABOLISM AND ARYL HYDROCARBON RECEPTOR DISTRIBUTION IN RODENT POLYCYSTIC KIDNEYS

2021 ◽  
Vol 6 (4) ◽  
pp. S187
Author(s):  
S. Nagao ◽  
K. Kumamoto ◽  
M. Kugita ◽  
A. Yoshimura ◽  
R. Murakami ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Tryptophan Metabolism ◽  
Polycystic Kidneys ◽  
Aryl Hydrocarbon ◽  
Altered Regulation ◽  
Receptor Distribution

scholarly journals A42 MICROBIAL METABOLISM OF DIETARY TRYPTOPHAN ENHANCES ARYL HYDROCARBON RECEPTOR ACTIVATION: IMPLICATIONS FOR IBD

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 50-51
Author(s):  
L Rondeau ◽  
A V Clarizio ◽  
J Jury ◽  
D L Gibson ◽  
P Bercik ◽  
...  
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
Aryl Hydrocarbon Receptor ◽  
Healthy Subjects ◽  
Tryptophan Metabolism ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Aryl Hydrocarbon ◽  
Deficient Mice ◽  
Activation Capacity

Abstract Background Intestinal immune homeostasis is maintained by the interplay between microbiota and the mucosal immune system. Changes in gut microbiota have been associated with chronic intestinal conditions, such as inflammatory bowel disease (IBD). The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by dietary and environmental stimuli to control immune responses in the gut and homeostatic mechanisms at mucosal surfaces. In IBD, AhR expression is downregulated. Major agonists of AhR in the gut include microbial tryptophan metabolites such as indole derivatives, which are decreased in IBD patients. The mechanisms involved in tryptophan metabolism by bacteria and their implications in AhR activation and thus IBD pathogenesis are not well understood. Aims To investigate whether tryptophan metabolism by intestinal bacteria participates in AhR activation and IBD pathogenesis. Methods Microbiota profiles (16S rRNA Illumina) and activation of AhR (luciferase reporter assay) were determined in fecal samples from IBD patients (n=10) and healthy volunteers (n=10). Germ-free C57BL/6 mice were colonized with fecal slurries of 2 healthy subjects and 4 IBD patients (n=4 mice/donor) by oral gavage (humanized-mice). All mice were fed irradiated tryptophan diets with 0.1% or 1% tryptophan content for 14 days. Simultaneously, SPF Mucin 2 (Muc2) deficient mice (C57BL/6 background), which develop colitis spontaneously, were fed tryptophan diets (0.1%, 0.3% and 1% content). Activation of AhR was measured in feces using an AhR luciferase reporter assay. Inflammation was determined by immunohistochemistry and the characterization of immune infiltrate in colon cross-sections. Bacteria from human and mouse fecal samples were isolated and screened for their ability to produce indoles using biochemical reagents. Positive bacteria were identified by colony PCR and 16S rRNA Sanger sequencing. Results IBD patients had an altered fecal microbiota with a lower capacity to activate AhR compared to healthy subjects. Colonization of mice with microbiota from healthy subjects induced greater activation of AhR compared to mice colonized with microbiota from patients with IBD. Furthermore, increasing dietary tryptophan composition rescued the capacity to activate AhR. In Muc2 deficient mice, dietary tryptophan treatment enhanced AhR activation capacity and reduced infiltration of innate immune cells before the onset of colitis. Several AhR agonist producing bacterial species were identified and will be used in future experiments. Conclusions Activation of AhR is dependent on the gut microbiota and disease status of the donor. Dietary intervention with tryptophan enhances AhR activation capacity and may be a potential therapeutic avenue in IBD individuals with intestinal dysbiosis. Funding Agencies Farncombe Family Digestive Health Research Institute, Biocodex Microbiota Foundation

scholarly journals Investigation of the aryl hydrocarbon receptor and the intrinsic tumoral component of the kynurenine pathway of tryptophan metabolism in primary brain tumors

2018 ◽  
Vol 139 (2) ◽  
pp. 239-249 ◽  
Author(s):  
Anthony R. Guastella ◽  
Sharon K. Michelhaugh ◽  
Neil V. Klinger ◽  
Hassan A. Fadel ◽  
Sam Kiousis ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Aryl Hydrocarbon Receptor ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Primary Brain Tumors ◽  
Aryl Hydrocarbon

scholarly journals Aryl hydrocarbon receptor activation by Lactobacillus reuteri tryptophan metabolism alleviates Escherichia coli-induced mastitis in mice

2021 ◽  
Vol 17 (7) ◽  
pp. e1009774
Author(s):  
Caijun Zhao ◽  
Xiaoyu Hu ◽  
Lijuan Bao ◽  
Keyi Wu ◽  
Lianjun Feng ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Aryl Hydrocarbon Receptor ◽  
Intestinal Microbiota ◽  
Lactobacillus Reuteri ◽  
Underlying Mechanism ◽  
Receptor Activation ◽  
Tryptophan Metabolism ◽  
Dependent Manner ◽  
Aryl Hydrocarbon ◽  
Novel Therapeutic Strategies

The intestinal microbiota has been associated with the occurrence and development of mastitis, which is one of the most serious diseases of lactating women and female animals, but the underlying mechanism has not yet been elucidated. Aryl hydrocarbon receptor (AhR) activation by microbiota tryptophan metabolism-derived ligands is involved in maintaining host homeostasis and resisting diseases. We investigated whether AhR activation by microbiota-metabolic ligands could influence mastitis development in mice. In this study, we found that AhR activation using Ficz ameliorated mastitis symptoms, which were related to limiting NF-κB activation and enhancing barrier function. Impaired AhR activation by disturbing the intestinal microbiota initiated mastitis, and processed Escherichia coli (E. coli)-induced mastitis in mice. Supplementation with dietary tryptophan attenuated the mastitis, but attenuation was inhibited by the intestinal microbiota abrogation, while administering tryptophan metabolites including IAld and indole but not IPA, rescued the tryptophan effects in dysbiotic mice. Supplementation with a Lactobacillus reuteri (L. reuteri) strain with the capacity to produce AhR ligands also improved E. coli-induced mastitis in an AhR-dependent manner. These findings provide evidence for novel therapeutic strategies for treating mastitis, and support the role of metabolites derived from the intestinal microbiota in improving distal disease.

scholarly journals The Aryl Hydrocarbon Receptor: A Review of Its Role in the Physiology and Pathology of the Integument and Its Relationship to the Tryptophan Metabolism

2015 ◽  
Vol 8 ◽  
pp. IJTR.S19985 ◽  
Author(s):  
Rowland Noakes
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Immune Regulation ◽  
Presidential Elections ◽  
Therapeutic Agent ◽  
Tryptophan Metabolism ◽  
Low Molecular Weight ◽  
Aryl Hydrocarbon ◽  
Cellular Oxidation ◽  
Cytosolic Receptor

The aryl hydrocarbon receptor (AHR) is a cytosolic receptor for low molecular weight molecules, of which the most widely recognized ligand is 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), and the most widely recognized effect, chloracne. Adverse effects of manipulation were most recently and graphically demonstrated by the poisoning of Viktor Yushchenko during the Ukrainian presidential elections of 2004. However, recent research has revealed a receptor with wide-ranging, and at times, paradoxical actions. It was arguably among the first biological receptors to be utilized by dermatologists, dating from the time of topical tar preparations as a therapeutic agent. I provide a review outlining the role AHR plays in the development, cellular oxidation/antioxidation, responses to ultraviolet light, melanogenesis, epidermal barrier function, and immune regulation and its relationship to tryptophan metabolism. Finally, I will review the role of AHR in diseases of the integument.

scholarly journals Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas

Nature Cancer ◽  
2021 ◽  
Author(s):  
Mirco Friedrich ◽  
Roman Sankowski ◽  
Lukas Bunse ◽  
Michael Kilian ◽  
Edward Green ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Late Stage ◽  
Cell Response ◽  
Isocitrate Dehydrogenase ◽  
Myeloid Cells ◽  
T Cell Response ◽  
Tryptophan Metabolism ◽  
Aryl Hydrocarbon ◽  
Single Cell Profiling ◽  
Altered Metabolism

AbstractThe dynamics and phenotypes of intratumoral myeloid cells during tumor progression are poorly understood. Here we define myeloid cellular states in gliomas by longitudinal single-cell profiling and demonstrate their strict control by the tumor genotype: in isocitrate dehydrogenase (IDH)-mutant tumors, differentiation of infiltrating myeloid cells is blocked, resulting in an immature phenotype. In late-stage gliomas, monocyte-derived macrophages drive tolerogenic alignment of the microenvironment, thus preventing T cell response. We define the IDH-dependent tumor education of infiltrating macrophages to be causally related to a complex re-orchestration of tryptophan metabolism, resulting in activation of the aryl hydrocarbon receptor. We further show that the altered metabolism of IDH-mutant gliomas maintains this axis in bystander cells and that pharmacological inhibition of tryptophan metabolism can reverse immunosuppression. In conclusion, we provide evidence of a glioma genotype-dependent intratumoral network of resident and recruited myeloid cells and identify tryptophan metabolism as a target for immunotherapy of IDH-mutant tumors.

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