Renoprotective Effect of <i>Coix lachryma‐jobi</i> L. Seed Polysaccharides in Adenine‐Induced Chronic Renal Failure by Blocking Gut Urea Metabolism

ABSTRACT Dietary soluble fiber may alleviate renal damage in chronic kidney disease (CKD) by promoting intestinal urea excretion, though the underlying mechanisms remain unclear. This study investigated the digestion, fermentation, and renoprotective effects of Coix lachryma‐jobi L. seed polysaccharides (CP) using in vitro systems and adenine‐induced CKD mice. CP resisted gastric and small intestinal digestion but was effectively fermented by human gut microbiota, exhibiting effective urease inhibitory activity and reducing ammonia production in vitro. In CKD mice, CP treatment ameliorated renal histopathology, reduced serum creatinine, phosphorus, calcium, and fecal p ‐cresol, indole, while increasing urinary and fecal urea excretion and decreasing fecal ammonia. CP reshaped the gut microbiota, reducing Parabacteroides, Anaeroplasma, and other genera linked to amino acid metabolism (all p &lt; 0.05), which positively correlated with p ‐cresol and serum creatinine. Conversely, Lactobacillus were enriched (p &lt; 0.01) and negatively correlated with toxin levels, while positively correlated with the excretion of urea and ammonia in urine. These findings suggested CP improved renal function by modulating gut microbiota to suppress urease activity and aromatic amino acid metabolism, thereby reducing uremic toxin production and enhancing nitrogenous waste elimination via the gut–kidney axis.