Gut microbiota-derived tryptophan metabolism mediates renal fibrosis by aryl hydrocarbon receptor signaling activation.

Abstract

The gut microbiota has a crucial effect on regulating the intestinal mucosal immunity and maintaining intestinal homeostasis both in health and in disease state. Many effects are mediated by gut microbiota-derived metabolites and tryptophan, an essential aromatic amino acid, is considered important among many metabolites in the crosstalk between gut microbiota and the host. Kynurenine, serotonin, and indole derivatives are derived from the three major tryptophan metabolism pathways modulated by gut microbiota directly or indirectly. Aryl hydrocarbon receptor (AHR) is a cytoplasmic ligand-activated transcription factor involved in multiple cellular processes. Tryptophan metabolites as ligands can activate AHR signaling in various diseases such as inflammation, oxidative stress injury, cancer, aging-related diseases, cardiovascular diseases (CVD), and chronic kidney diseases (CKD). Accumulated uremic toxins in the body fluids of CKD patients activate AHR and affect disease progression. In this review, we will elucidate the relationship between gut microbiota-derived uremic toxins by tryptophan metabolism and AHR activation in CKD and its complications. This review will provide therapeutic avenues for targeting CKD and concurrently present challenges and opportunities for designing new therapeutic strategies against renal fibrosis.

• Authors: Jing-Ru Liu, Hua Miao, De-Qiang Deng, Nosratola D Vaziri, Ping Li, Ying-Yong Zhao
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 78 Issue 3 Pg. 909-922 (Feb 2021) ISSN: 1420-9071 [Electronic] Switzerland
• PMID: 32965514 (Publication Type: Journal Article, Review)

Chemical References

• Biological Products
• Indoleacetic Acids
• Polycyclic Aromatic Hydrocarbons
• Receptors, Aryl Hydrocarbon
• indoleacetic acid
• Tryptophan
• Cytochrome P-450 CYP2E1

Topics

• Biological Products (chemistry, metabolism)
• Cytochrome P-450 CYP2E1 (metabolism)
• Gastrointestinal Microbiome
• Humans
• Indoleacetic Acids (chemistry, metabolism)
• Polycyclic Aromatic Hydrocarbons (chemistry, metabolism)
• Receptors, Aryl Hydrocarbon (agonists, antagonists & inhibitors, metabolism)
• Renal Insufficiency, Chronic (metabolism, pathology)
• Signal Transduction
• Tryptophan (metabolism)