Altered Intestinal Microbial Flora and Metabolism in Patients with Idiopathic Membranous Nephropathy

<b><i>Introduction:</i></b> Dysbiosis of the intestinal microbiome and related metabolites have been observed in chronic kidney disease, yet their roles in idiopathic membranous nephropathy (IMN) are poorly understood. <b><i>Methods:</i></b> In this study, we describe the variation of intestinal bacteria and fecal metabolites in patients with IMN in Chinese population. Stool samples were collected from 41 IMN patients at the beginning of diagnosis confirmation and 41 gender- and age-matched healthy control (HC). Microbial communities are investigated by sequencing of 16S rRNA genes and functional profiles predicted using Tax4Fun, and the correlation between intestinal bacteria and IMN clinical characteristics is also analyzed. Untargeted metabolomic analysis is performed to explore the relationship between colon’s microbiota and fecal metabolites. <b><i>Results:</i></b> IMN gastrointestinal microbiota demonstrates lower richness and diversity compared to HC, and exhibits a marked taxonomic and inferred functional dysbiosis when compared to HC. Some genera are closely related to the clinical parameters, such as <i>Citrobacter</i> and <i>Akkermansia</i>. Twenty characteristic microbial biomarkers are selected to establish a disease prediction model with a diagnostic accuracy of 93.53%. Fecal metabolomics shows that tryptophan metabolism is reduced in IMN patients but uremic toxin accumulation in feces is not noticeable. Fecal microbiota transplantation demonstrates that gut dysbiosis impairs gut permeability in microbiota-depleted mice and induces NOD-like receptor activation in the kidneys. <b><i>Conclusions:</i></b> Clarifying the changes in intestinal microbiota in IMN patients will help further know the pathogenesis of this disease, and microbiota-targeted biomarkers will provide a potentially powerful tool for diagnosing and treating IMN.