Evidence from mendelian randomization identifies several causal relationships between primary membranous nephropathy and gut microbiota.
Renal failure
BACKGROUND:Research has showcased a correlation between disruptions in gut microbiota and primary membranous nephropathy (pMN), giving rise to the concept of the 'gut-kidney axis'. However, the precise relationship between gut microbiota and pMN remains elusive. Hence, this study endeavors to investigate whether a causal relationship exists between gut microbiota and pMN utilizing Mendelian randomization (MR) analysis. METHODS:The primary method employed for MR analysis is the inverse variance weighting method, supplemented by MR-Egger and the weighted median method, to infer causality. This approach was validated within the pMN cohort across two distinct populations. RESULTS:At the species level, the abundance of and was negatively correlated with the risk of pMN. Conversely, pMN was positively associated with abundance at the class level, abundance at the family level, and abundance at the genus level. Specifically, at the species level, pMN was positively correlated with the abundance of , , and CONCLUSION:These findings lay the groundwork for future research exploring the interplay between pMN and the gut microbiota, with substantial implications for the prevention and treatment of pMN and its associated complications.
10.1080/0886022X.2024.2349136
Lactobacillus species ameliorate membranous nephropathy through inhibiting the aryl hydrocarbon receptor pathway via tryptophan-produced indole metabolites.
British journal of pharmacology
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. EXPERIMENTAL APPROACH: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). KEY RESULTS: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.
10.1111/bph.16219
Fecal microbiota transplantation for membranous nephropathy.
Zhou Guanzhou,Zeng Jiaqi,Peng Lihua,Wang Lei,Zheng Wei,Di Wu ,Yang Yunsheng
CEN case reports
Membranous nephropathy is a pathological type of nephrotic syndrome. Current treatments including supportive therapy, corticosteroids, immunosuppressive agents are not effective for all patients. New therapies are needed to treat the disease safely and effectively. Gut microbiota may contribute to the pathogenesis of this disease. Fecal microbiota transplantation (FMT) has made achievements in many diseases. Here, we report a case in which FMT is used to treat a patient with membranous nephropathy and chronic diarrhea, whose symptoms ameliorated and renal function improved.
10.1007/s13730-020-00560-z