The causal association of specific gut microbiota on the risk of
membranous nephropathy: a Mendelian randomization study
Abstract
Gut microbiota transplantation has been reported to improve the renal
function of membranous nephropathy (MN). However, whether there is a
causal effect of gut microbiota on MN remained unclear. We performed
two-sample Mendelian randomization (MR) analysis. The inverse variance
weighted (IVW) method was used as the main approach to evaluate the
causal relationship between gut microbiota and MN. Additional methods
including MR-Egger regression, weighted median, and MR-weighted mode
were also conducted. Cochrane’s Q test, MR-Egger regression, and
MR-PRESSO were employed to detect heterogeneity and pleiotropy,
respectively. A total of 196 gut microbiota were examined. After IVW and
sensitivity analysis, eight gut bacteria taxa were observed causal
effects on the risk of MN. Specifically, Genus. Oscillibacter was a
protective factor (OR: 0.57; 95%CI: 0.328-0.979; P = 0.042), while
Class. Melainabacteria (OR: 1.51; 95% CI: 1.004-2.277; P = 0.048),
Genus. Butyricicoccus (OR: 2.16; 95% CI: 1.005-4.621; P = 0.048),
Genus. Catenibacterium (OR: 1.49; 95% CI: 1.043-2.134; P = 0.028),
Genus.Ruminiclostridium5 (OR: 1.74; 95% CI: 1.053-2.862; P = 0.030),
Genus. Ruminococcaceae UCG-003 (OR: 1.73; 95% CI: 1.110-2.692; P =
0.015), Order. Bacillales (OR: 1.52; 95% CI:1.135-2.025; P = 0.0048)
and Order. Gastranaerophilales (OR: 1.45; 95% CI: 1.010-2.085; P =
0.044) were risk factors. Heterogeneity was not significant for most
single-nucleotide polymorphisms, and no statistical difference in
pleiotropy. This study first indicated the causal association between
specific gut microbiota and MN, which would be of great significance to
guide clinical prevention and treatment in MN.