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The aim is to establish a non\u2010invasive diagnostic model of MN using differential gut microbiome analysis, and to explore the relationship between the gut microbiome and MN pathogenesis in vivo. 825 fecal samples from MN patients and healthy participants are collected from multiple medical centers across China. Key operational taxonomic units (OTUs) obtained through 16S rRNA sequencing are used to establish a diagnostic model. A rat model of MN is developed to explore the relationship between the gut microbiome and the pathogenesis of MN. The diversity and richness of the gut microbiome are significantly lower in patients with MN than in healthy individuals. The diagnostic model based on seven OTUs achieves an excellent efficiency of 98.36% in the training group and also achieves high efficiency in cross\u2010regional cohorts. In MN rat model, gut microbiome elimination prevents model establishment, but fecal microbiome transplantation restores the phenotype of protein urine. Gut microbiome analysis can be used as a non\u2010invasive tool for MN diagnosis. The onset of MN depends on the presence of naturally colonized microbiome. Early intervention in the gut microbiome may help reduce urinary protein level in MN.<\/jats:p>","DOI":"10.1002\/advs.202201581","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T03:13:04Z","timestamp":1660705984000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Gut Microbiome Analysis Can Be Used as a Noninvasive Diagnostic Tool and Plays an Essential Role in the Onset of Membranous Nephropathy"],"prefix":"10.1002","volume":"9","author":[{"given":"Jin","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan 450052 China"},{"name":"Zhengzhou University  Zhengzhou Henan 450000 P. R. 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