Weissella cibaria-derived dextran alleviates cisplatin-induced kidney injury by remodeling the gut microbiota

Cisplatin, a first-line chemotherapeutic agent, is severely limited by its dose-limiting nephrotoxicity. The gut-kidney axis has emerged as a critical pathway, where cisplatin-induced intestinal injury aggravates renal damage. While exopolysaccharides (EPS) from probiotics are known for health benefits, their role against cisplatin toxicity is unclear. This study aimed to investigate the protective effects and mechanisms of EPS-2, a dextran from Weissella cibaria MW030, against cisplatin-induced acute kidney injury.

Pretreatment with EPS‑2 significantly alleviated renal histopathological damage, apoptosis, oxidative stress, and inflammation, while also restoring intestinal barrier integrity by enhancing mucin and tight junction protein expression. Gut microbiota analysis indicated that EPS‑2 enriched short-chain fatty acids (SCFAs)‑producing bacteria such as unclassified_f_Muribaculaceae and suppressed LPS‑producing potential pathogens including Escherichia‑Shigella. These compositional changes were accompanied by elevated fecal SCFA levels and reduced circulating LPS, which may collectively contribute to the mitigation of renal injury. Notably, these protective effects were abolished in pseudo‑germ‑free mice, underscoring the critical role of the gut microbiota in the action of EPS‑2.

EPS-2 has the potential to be a promising postbiotic for preventing cisplatin-induced AKI, intestinal barrier dysfunction, and gut microbiota dysbiosis.