Intestinal microflora changes in patients with immunoglobulin A nephropathy and membranous nephropathy

Abstract:

[Background] There is increasing evidence that intestinal imbalance is associated with immune-mediated disease. However, the mechanistic link between intestinal flora and immune-mediated kidney disease remains unclear. [Objective] To compare the intestinal flora by using high throughput 16S ribosomal RNA (rRNA) gene sequencing between patients with immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) and healthy people. [Methods] Fresh fecal samples from patients with IgAN and MN who underwent renal biopsy in the Department of Nephrology of Gansu Provincial Hospital from September 2020 to December 2021 were retrospectively selected and divided into an IgAN group and a MN group, and the fecal samples from healthy people in the physical examination center were collected as a healthy control group, with 10 cases in each group. The 16S rRNA gene V3−V4 region of all bacteria in fecal samples was sequenced by high-throughput sequencing technology, and then biodiversity analysis was performed, including operational taxonomic units (OTU) analysis, species classification analysis, alpha diversity analysis, beta diversity analysis, etc., to compare the intestinal flora differences among the three groups. [Results] As compared with the healthy control group, Proteobacteria and Actinobacteria at phylum level in the IgAN group were significantly increased (18% vs. 4% and 18.3% vs. 5%, respectively). The abundance of Escherichia-Shigella and Bifidobacterium at genus level was significantly higher in the IgAN group (14.1% vs. 2.1% and 17.5% vs. 4.7%, respectively), while the abundance of Faecalibacterium (11% vs. 20.5%), Bacteroides (8.0% vs. 21%), and Megomonas (1.8% vs. 8.0%) was significantly lower. The abundance of Proteobacteria at phylum level increased in the MN group as compared with the healthy control group (20% vs. 4%). At genus level, the abundance of Escherich-Shigella increased in the MN group (13.8% vs 2.1%), the abundance of Bifidobacteria (3.2% vs. 4.7%), Faecalibacterium (18% vs. 20.5%), Bacteroides (14.3% vs. 21%), and Megomonas (1% vs. 8%) decreased. Alpha diversity analysis showed that the richness index of the IgAN and MN groups was lower than that of the healthy control group, and the diversity index was higher than that of the healthy control group. Principal coordinates analysis (PCoA) showed statistically significant differences in the composition of intestinal flora between the IgAN group and the healthy control group (ANOISM, R=0.19, P=0.013). There were differences in the composition of intestinal flora between the MN group and the healthy control group, but the results were not statistically significant (ANOISM, R=0.08, P=0.08). Linear discriminant analysis (LDA) for differential contribution revealed that 14 species had significant differences among the three groups. [Conclusion] The intestinal microbiome characteristics of patients with IgAN and MN are different from those of healthy people.