Lactobacillus species ameliorate membranous nephropathy through inhibiting the aryl hydrocarbon receptor pathway via tryptophan-produced indole metabolites.
Br J Pharmacol
; 181(1): 162-179, 2024 01.
Article
en En
| MEDLINE
| ID: mdl-37594378
ABSTRACT
BACKGROUND AND PURPOSE:
Membranous nephropathy (MN) is an immune-mediated glomerular disease in adults. Antibody- and antigen-bonding mechanisms have been largely clarified, but the subepithelium immune complex deposition-mediated downstream molecular mechanisms are currently unresolved. Increasing evidence has suggested that gut microbiota contribute to MN pathogenesis. EXPERIMENTALAPPROACH:
In this study, we identified alterations in faecal gut microbiota and serum metabolites that mediate an aryl hydrocarbon receptor (AhR) mechanism in cationic bovine serum albumin (CBSA)-induced MN rats and in patients with idiopathic MN (IMN). KEYRESULTS:
Impaired renal function correlated with the relative abundance of reduced faecal probiotics, Lactobacillus and Bifidobacterium, and altered serum levels of tryptophan-produced indole derivatives (TPIDs) in MN rats. Further results showed that reduced relative abundance of five probiotics, namely Lactobacillus johnsonii, Lactobacillus murinus, Lactobacillus vaginalis, Lactobacillus reuteri and Bifidobacterium animalis, positively correlated with decreased levels of indole-3-pyruvic acid, indole-3-aldehyde and tryptamine and negatively correlated with increased levels of indole-3-lactic acid and indole-3-acetic acid in serum of MN rats. Altered five probiotics and five TPIDs also were observed in patients with IMN. Further studies showed that MN rats exhibited a significant increase in intrarenal mRNA expression of AhR and its target genes CYP1A1, CYP1A2 and CYP1B1, which were accompanied by protein expression of down-regulated cytoplasmic AhR, but up-regulated nuclear AhR, in MN rats and IMN patients. CONCLUSION AND IMPLICATIONS Activation of the intrarenal AhR signalling pathway may involve five TPIDs. These data suggest that gut microbiota could influence MN through TPIDs that engage host receptors.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_zoonosis
Asunto principal:
Glomerulonefritis Membranosa
/
Receptores de Hidrocarburo de Aril
/
Microbioma Gastrointestinal
/
Indoles
/
Lactobacillus
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Br J Pharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China