Increased gut permeability with altered gut microbiota and fecal metabolome in rats with adriamycin-induced nephropathy

Primary nephrotic syndrome (PNS) is a common glomerular disease in children and adults. The most common pathological type of childhood PNS is minimal change nephrotic syndrome (MCNS). The underlying mechanism of MCNS is largely unknown. Adriamycin-induced nephropathy rat model has been also widely used for studying MCNS. Meanwhile, it has been shown that the gut-renal axis has been implicated in PNS. However, it remains un-known what is the gut-side profile of gut-renal axis in adriamycin-induced nephropathy rat model. Thus, this study aimed to investigate the gut permeability, gut microbiota and fecal metabolites in rats with adriamycin-induced nephropathy.Our data showed gut permeability increased significantly in rats with adriamycin-induced nephropathy. Accordingly, tight junction in rat ileum was dilated as shown under transmission electron microscopy. The profiles of gut micro-biota at taxonomic levels have changed in rats 6 weeks after adriamycin treatment. Particularly, the concentration of 37 fecal metabolites increased significantly, while 9 fecal metabolites decreased. Conclusions: Our findings suggested that adriamycin-induced nephropathy rat model was marked with increased gut permeability, altered gut microbiota and fecal metabolites. It might help to understand the pathogenesis of MCNS in the aspect of gut-renal axis as well as the pharmacology of Adriamycin.