Heat-KilledHY2782 Attenuates Chronic Kidney Disease by Suppressing Inflammation and Selectively Modulating the Gut Microbial Community.

Abstract

Chronic kidney disease (CKD) is a progressive disorder characterized by renal dysfunction, chronic inflammation, and gut microbial dysbiosis. In this study, we investigated the protective effect of heat-killedHY2782 (HY2782) in an adenine-induced CKD mouse model. Mice were evaluated for serum renal function markers, renal histopathology, inflammatory and barrier-related gene expression, and gut microbial composition. Oral administration of HY2782 significantly reduced serum blood urea nitrogen and creatinine levels and ameliorated renal histopathological damage, including tubular dilatation, cast formation, composite kidney injury, and mononuclear cell infiltration. In kidney tissue, HY2782 suppressed the CKD-associated upregulation of pro-inflammatory cytokine- and TLR4/NF-κB-related genes. In colon tissue, HY2782 attenuated the expression of pro-inflammatory cytokines and inflammatory signaling-related genes and showed a partial recovery trend in tight junction-related gene expression. Gut microbiota analysis revealed no significant changes in alpha diversity, whereas beta diversity was significantly altered by HY2782 treatment, indicating selective restructuring of the microbial community. At the taxonomic level, HY2782 significantly reducedabundance and showed a recovery trend in, and correlation analysis further indicated that these taxa were associated with renal dysfunction and inflammatory markers. Collectively, these findings suggest that heat-killed HY2782 attenuates adenine-induced CKD in association with suppression of renal and intestinal inflammation and selective modulation of gut microbiota, supporting its potential as a postbiotic candidate for CKD management.