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.