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The development of chronic kidney disease (CKD) and its progression to end-stage renal disease (ESRD), have been a major source of reduced quality of life and significant premature mortality. Previously, we have identified that levels of specific microbial species were significantly altered across early to advanced stages of CKD.
In the present study, we tested whether these is a causal effect of one such bacterial candidate, Phocaeicola plebeius (formerly Bacteroides plebeius), on renal health by manipulating the gut microbiota in a mouse model of CKD.
We showed that colonization of P. plebeius in the mouse model of CKD by oral gavage ameliorated the morphological and functional changes in the kidney. In particular, oral administration of P. plebeius reduced the levels of proteinuria and podocyte foot process effacement as monitored through the urine albumin to creatinine ratio and electron microscopic analysis, respectively. Further examination of the renal tissues from P. plebeius-treated CKD mice by using RNA sequencing revealed an involvement of altered immune responses in the mouse kidney. Specifically, the elevation in the expression levels of genes associated with renal inflammation by systematic metabolic abnormalities was reversed by gut colonization of P. plebeius. Moreover, gene expression profiles of colon tissues from P. plebeius-treated CKD mice showed that genes related to endotoxic shock responses were differentially expressed, highlighting a role of the gut-kidney axis in renal impairment.
These experimental findings implicate P. plebeius as a promising live biotherapeutic product for CKD, providing potential avenues for microbiome-based modality of renal insufficiency.