Dietary inulin mediates the molecular mechanism of intestinal metabolites to alleviate high salt diet-induced chronic kidney disease in mice.

It is recognized that excessive dietary salt intake is a critical factor contributing to chronic kidney disease (CKD). A high-salt diet (HSD) disrupts the balance of the gut microbiota, but the molecular mechanisms linking gut dysbiosis to target organ damage remain unclear. This study identified dietary prebiotic inulin (INU) as a potent regulator of the gut-short-chain fatty acid-kidney axis, capable of counteracting HSD-induced CKD. Sequencing analysis showed that INU selectively enriched Bifidobacterium and Faecalibaculum while downregulating Desulfovibrio. This microbiome shift restored intestinal tight junction proteins and reduced serum lipopolysaccharide (LPS) levels, thereby inhibiting TLR4/NF-κB-mediated renal inflammation. Notably, the effects of direct SCFA supplementation align with the renal protective effects of INU, confirming the critical role of the gut-kidney axis. Our study reveals INU as a dietary strategy that combats HSD-induced CKD via SCFAs produced by the microbiota, offering new insights into the gut-SCFAs-kidney axis as a therapeutic target.