Introduction
Membranous nephropathy (MN) has been the most frequent pathological type
of nephrotic syndrome in adults [1]. Over decades, the rapid
development of immunomodulatory therapy has achieved remarkable results
in delaying the progression of the disease. Nevertheless, the
accompanying adverse reactions have also become challenging problems
that many scholars need to solve urgently. Therefore, it is necessary to
find better approaches to prevent and intervene in MN in clinical
practice.
Gut bacteria are integral parts of the human body, acquired at birth and
changed dynamically with the increase of age [2]. In recent years,
intestinal flora imbalance has been reported to participate in a variety
of diseases such as metabolic-related diseases, tumors, aging, etc.
[3-5]. Of note, there is an increasing literature evidence that gut
bacteria are also related to various kidney diseases, such as
immunoglobulin A nephropathy, diabetic kidney disease, etc. [6, 7].
In addition, the concept of the gut-kidney axis further indicated a
close relationship between gut bacteria and the kidney [8].
Recently, Zhou et al reported the successful use that fecal microbiota
transplantation improved renal function in a MN patient with chronic
diarrhea [9], which suggests the mysterious association of gut
microbiota on MN. However, whether there is a causal link between
intestinal flora imbalance and the risk of MN is currently still
unclear.
Mendelian randomization (MR) analysis is a recently proposed research
method that is based on Mendel’s second law to simulate randomized
controlled trials. The causal correlation between exposure and outcomes
could be confirmed at the genetic level by using single-nucleotide
polymorphisms (SNPs) as instrumental variables and are not interfered by
confounding variables [10]. Compared with observational research, MR
analysis has more accurate to analyze the causal relationship between
exposure and outcomes.
Given above, we conducted this MR analysis aiming to clarify the
potential causal effects of gut microbiota on the risk of MN and to
reveal the specific bacterial taxa, which would be of great significance
for more precise targeted regulation of bacteria to prevent and
intervene the MN.