Early Remodeling of Gut Microbiota and Plasma Metabolome in IgA Nephropathy-Derived Uremic Patients After Kidney Transplantation: A Multi-Omics Study

Background IgA nephropathy (IgAN) is a leading cause of end-stage renal disease (ESRD), with kidney transplantation as the preferred treatment for uremic patients. Gut microbiota dysbiosis is closely associated with IgAN pathogenesis, uremia progression, and post-transplant complications. However, longitudinal data on early post-transplant gut microbiota and metabolome remodeling in IgAN-derived ESRD patients remain scarce. We aimed to characterize these changes and their correlations to inform post-transplant management. Methods We enrolled 28 uremic patients with biopsy-confirmed primary IgAN (Uremia), 20 of whom completed kidney transplantation with paired fecal and plasma samples collected before surgery and on post-kidney transplantation day 15 (KT). Another 28 healthy volunteers were included as controls (Control). All samples were analyzed by 16S rRNA gene amplicon sequencing and plasma non-targeted metabolomics. Results Early after kidney transplantation, patients showed persistently reduced gut microbiota diversity compared with Control, with no significant change in species richness but further decreased microbial evenness versus pre-transplant uremic state. The microbial community structure was significantly restructured, characterized by downregulation of beneficial bacteria and enrichment of opportunistic pathogens. Plasma metabolome was significantly remodeled, with 503 and 371 differential metabolites identified versus Uremia and Control, respectively; uremic toxins such as indoxyl sulfate and creatinine were significantly reduced, while arginine and proline metabolism pathway was persistently altered in both comparisons. Correlation analysis preliminarily identified potential statistical associations between key gut bacterial genera and differential metabolites, as well as between Gemmiger and plasma tacrolimus trough concentration in this cohort. Conclusion This study adopted a early paired self-controlled design to systematically characterize post-transplant gut microbiota and plasma metabolome changes in a cohort of patients with IgAN-derived uremia, and preliminarily depicted their remodeling patterns under standardized perioperative management, providing preliminary correlative evidence and clues for elucidating the gut-kidney axis in kidney transplantation and guiding early postoperative clinical management.