A Comparative Study of the Gut Microbiota Associated With Immunoglobulin a Nephropathy and Membranous Nephropathy Original paper

What Was Studied?

This study investigated the association between gut microbiota composition and two glomerular diseases: Immunoglobulin A Nephropathy (IgAN) and Membranous Nephropathy (MN). By comparing 44 patients with IgAN, 40 patients with MN, and 30 healthy controls, the researchers analyzed fecal microbiota using 16S rDNA sequencing to identify microbial taxa associated with these diseases and their potential as biomarkers for diagnosis and contributors to pathogenesis.

Who Was Studied?

The study included 44 IgAN patients, 40 MN patients, and 30 healthy controls. All participants were biopsy-confirmed, and none had taken antibiotics, probiotics, or immunosuppressive therapy prior to sampling. Demographic factors, such as age, sex, and body mass index (BMI), were matched across groups. Patients with secondary glomerulonephritis, gastrointestinal disorders, pregnancy, or other autoimmune diseases were excluded.

What Were the Most Important Findings?

The study revealed distinct gut microbial signatures in patients with Immunoglobulin A Nephropathy (IgAN) and Membranous Nephropathy (MN) compared to healthy controls. In IgAN, there was an enrichment of Escherichia-Shigella and Defluviitaleaceae_incertae_sedis, alongside a depletion of butyrate-producing genera such as Roseburia and Faecalibacterium. Notably, Klebsiella, Citrobacter, and Fusobacterium negatively correlated with serum albumin levels, while Prevotella showed a positive correlation.

In MN, patients exhibited increased abundances of Escherichia-Shigella, Peptostreptococcaceae_incertae_sedis, Streptococcus, and Enterobacteriaceae_unclassified, with a concurrent reduction in Lachnospira and Clostridium_sensu_stricto_1. Interestingly, Akkermansia muciniphila showed a protective association, correlating with lower IgG4 deposition in the subepithelial tissue.

Both IgAN and MN demonstrated shared alterations, including an increased prevalence of Proteobacteria at the phylum level and reduced butyrate-producing bacteria, which suggest common pathways involving inflammation and intestinal epithelial barrier dysfunction. However, there were distinct differences between the two diseases. IgAN had higher levels of Bilophila and Megasphaera, while MN patients exhibited greater abundances of Klebsiella, Enterococcus, and Streptococcus.

Correlation analyses further emphasized these differences. For instance, in IgAN, specific microbial genera were linked to clinical parameters, such as Prevotella correlating positively with serum albumin levels and Klebsiella and Citrobacter correlating negatively. In MN, Escherichia-Shigella negatively correlated with proteinuria, while Bacteroides showed a positive correlation with disease stage.

What Are the Greatest Implications?

The findings highlight gut microbial dysbiosis as a significant factor in the pathogenesis of IgAN and MN, supporting the concept of a gut-kidney axis. Further, these findings underline the potential for using microbial signatures as biomarkers for disease differentiation and as targets for therapeutic interventions. Major microbial associations (MMAs) such as Escherichia-Shigella and Roseburia, could serve as biomarkers or therapeutic targets. Butyrate-producing bacteria, depleted in both conditions, underline the potential for microbiota-targeted interventions (MBTIs), such as fecal microbiota transplantation (FMT) or targeted pre/probiotics, in managing these diseases. Furthermore, these microbial profiles offer insight into disease-specific mechanisms, opening avenues for precision medicine in nephrology. This study examined gut microbiota alterations in IgAN and MN, identifying unique and shared microbial changes linked to disease pathology. The findings suggest potential biomarkers and therapeutic targets through the gut-kidney axis.