Metagenomic Analysis Reveals Gut Microbiota Features in Membranous Nephropathy

Membranous nephropathy (MN) is one of the most common forms of primary glomerulonephritis worldwide and is closely associated with immune dysregulation. Increasing evidence suggests that the gut microbiota plays a critical role in regulating renal disease through the gut-renal axis. However, the use of metagenomic sequencing to analyze changes in the gut microbiota in patients with MN has not yet been reported.

This study employed a metagenomic approach to comprehensively analyze the gut microbiota in patients with MN (n = 10) and normal controls (NCs; n = 10). Shotgun metagenomic sequencing was performed on fecal samples. Microbial diversity, taxonomic composition, and functional pathways were assessed, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In addition, correlations between gut microbial characteristics and clinical indicators were also evaluated.

The gut microbial community in the MN group showed distinct differences from the control group, particularly with an increased abundance in phylum: Proteobacteria, Firmicutes_C, and Cyanobacteria; the genera Dialister, Selenomonadales, Clostridium, Bacillus, Megamonas, Romboutsia, and Inesitibacter; the species Bilophila_wadsworthia, Enterococcus_C, Megamonas funiformis, and Clostridium_perfringens. Furthermore, Bacillus_A showed a significant positive correlation with both serum creatinine and the protein-to-creatinine ratio. Conversely, higher levels of Victivallis were associated with lower blood urea nitrogen, while increased Fusicatenibacter was correlated with lower phospholipase A2 receptor levels. KEGG analysis indicated that the MN gut microbiota was enriched for pathways related to tryptophan metabolism, oxidative phosphorylation, and pathogenic Escherichia coli infection. Additionally, receiver operating characteristic analysis revealed that a four-genus model comprising enriched Dialister, Enterococcus_C, and Clostridium_P, and reduced Fusicatenibacter yielded an area under the curve of 0.90 ± 0.12, suggesting promising discriminatory potential that warrants further validation.

These findings demonstrate alterations in the composition and functional potential of the gut microbiota in patients with MN compared with the control group. Given the cross-sectional design of this study, these observations should be interpreted as associative, and further studies are required to validate these findings and explore any associated biological relevance.