Fisetin Improves Hyperuricemia-Induced Chronic Kidney Disease via Regulating Gut Microbiota-Mediated Tryptophan Metabolism and Aryl Hydrocarbon Receptor Activation

2021 ◽  
Author(s):  
Qian Ren ◽  
Lu Cheng ◽  
Fan Guo ◽  
Sibei Tao ◽  
Chunle Zhang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Tryptophan Metabolism ◽  
Aryl Hydrocarbon

scholarly journals Identification of endogenous 1‐aminopyrene as a novel mediator of progressive chronic kidney disease via aryl hydrocarbon receptor activation

2020 ◽  
Vol 177 (15) ◽  
pp. 3415-3435 ◽  
Author(s):  
Hua Miao ◽  
Gang Cao ◽  
Xia‐Qing Wu ◽  
Yuan‐Yuan Chen ◽  
Dan‐Qian Chen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Aryl Hydrocarbon

scholarly journals Aryl Hydrocarbon Receptor Activation in Chronic Kidney Disease: Role of Uremic Toxins

Nephron ◽  
2017 ◽  
Vol 137 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jessyca S. Brito ◽  
Natália A. Borges ◽  
Marta Esgalhado ◽  
D''Angelo C. Magliano ◽  
Christophe O. Soulage ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Uremic Toxins ◽  
Aryl Hydrocarbon

scholarly journals Maternal Tryptophan Supplementation Protects Adult Rat Offspring against Hypertension Programmed by Maternal Chronic Kidney Disease: Implication of Tryptophan-Metabolizing Microbiome and Aryl Hydrocarbon Receptor

2020 ◽  
Vol 21 (12) ◽  
pp. 4552 ◽  
Author(s):  
Chien-Ning Hsu ◽  
I-Chun Lin ◽  
Hong-Ren Yu ◽  
Li-Tung Huang ◽  
Mao-Meng Tiao ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Aryl Hydrocarbon Receptor ◽  
Female Rats ◽  
Adult Offspring ◽  
Sprague Dawley ◽  
Aryl Hydrocarbon ◽  
Induced Hypertension ◽  
In Pregnancy

Hypertension and chronic kidney disease (CKD) can originate during early-life. Tryptophan metabolites generated by different pathways have both detrimental and beneficial effects. In CKD, uremic toxins from the tryptophan-generating metabolites are endogenous ligands of the aryl hydrocarbon receptor (AHR). The interplay between AHR, nitric oxide (NO), the renin–angiotensin system (RAS), and gut microbiota is involved in the development of hypertension. We examined whether tryptophan supplementation in pregnancy can prevent hypertension and kidney disease programmed by maternal CKD in adult offspring via the aforementioned mechanisms. Sprague–Dawley (SD) female rats received regular chow or chow supplemented with 0.5% adenine for 3 weeks to induce CKD before pregnancy. Pregnant controls or CKD rats received vehicle or tryptophan 200 mg/kg per day via oral gavage during pregnancy. Male offspring were divided into four groups (n = 8/group): control, CKD, tryptophan supplementation (Trp), and CKD plus tryptophan supplementation (CKDTrp). All rats were sacrificed at the age of 12 weeks. We found maternal CKD induced hypertension in adult offspring, which tryptophan supplementation prevented. Maternal CKD-induced hypertension is related to impaired NO bioavailability and non-classical RAS axis. Maternal CKD and tryptophan supplementation differentially shaped distinct gut microbiota profile in adult offspring. The protective effect of tryptophan supplementation against maternal CKD-induced programmed hypertension is relevant to alterations to several tryptophan-metabolizing microbes and AHR signaling pathway. Our findings support interplay among tryptophan-metabolizing microbiome, AHR, NO, and the RAS in hypertension of developmental origins. Furthermore, tryptophan supplementation in pregnancy could be a potential approach to prevent hypertension programmed by maternal CKD.

Aryl Hydrocarbon Receptor and Uremic Toxins from the Gut Microbiota in Chronic Kidney Disease Patients: Is There a Relationship between Them?

Biochemistry ◽  
2019 ◽  
Vol 58 (15) ◽  
pp. 2054-2060 ◽  
Author(s):  
Jessyca Sousa de Brito ◽  
Natália Alvarenga Borges ◽  
Juliana Saraiva dos Anjos ◽  
Lia Sumie Nakao ◽  
Milena Barcza Stockler-Pinto ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Aryl Hydrocarbon Receptor ◽  
Uremic Toxins ◽  
Aryl Hydrocarbon

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 Aryl hydrocarbon receptor activation mediates kidney disease and renal cell carcinoma

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Hui Zhao ◽  
Lin Chen ◽  
Tian Yang ◽  
Ya-Long Feng ◽  
Nosratola D. Vaziri ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Receptor Activation ◽  
Aryl Hydrocarbon

Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease

2018 ◽  
Vol 93 (4) ◽  
pp. 986-999 ◽  
Author(s):  
Laetitia Dou ◽  
Stéphane Poitevin ◽  
Marion Sallée ◽  
Tawfik Addi ◽  
Bertrand Gondouin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon
Sign in / Sign up

Export Citation Format

Share Document