High-Dose Inulin Ameliorates Renal Function and Lipid Disorders but Does Not Optimize Gut Microecology in C57BL/6J Mice with Chronic Kidney Disease

Abstract Based on our clinical trial benefits of soluble dietary fibre in chronic kidney disease (CKD), we investigated the effects of 20% high-dose inulin (INU) in adenine-induced CKD mice. As expected, INU alleviated renal injury, reduced serum creatinine, and downregulated renal expression of inflammatory, fibrotic and STING-related molecules. It also improved serum lipid profiles, upregulated renal lipid metabolism genes, and remodelled serum lipidomic composition. Notably, inulin failed to elevate the main short-chain fatty acids (SCFAs) levels or beneficially reshape gut microbiota, and even enriched potential opportunistic pathogens. Therefore, the renoprotective and lipid-regulating effects of high-dose inulin are not primarily mediated by the gut microbiota-SCFAs axis. High-dose inulin ameliorates renal and lipid damage but shows limitations in optimizing gut microecology, providing experimental evidence for rational prebiotic application in CKD.