Polysaccharide from <i>Ribes nigrum L.</i> Ameliorates Diabetic Kidney Injury in Mice by Modulating the GUDCA/GPBAR1 Axis through the Remodeling of the Gut Microbiota

Diabetic nephropathy (DN) is a major microvascular complication of diabetes, requiring effective therapies. This study showed polysaccharide from <i>Ribes nigrum L.</i> (blackcurrant polysaccharides (BCP)) exerted therapeutic effects in high-fat diet/streptozotocin-induced diabetic mice, improving glucose homeostasis and alleviating renal inflammation and fibrosis. 16S rRNA sequencing revealed BCP altered gut microbiota and notably enriched <i>Akkermansia muciniphila</i>, which was validated via fecal microbiota transplantation and exogenous <i>A. muciniphila</i> administration. Combined 16S rRNA sequencing and metabolomic analysis identified a positive correlation between <i>A. muciniphila</i> and glycoursodeoxycholic acid (GUDCA). Exogenous <i>A. muciniphila</i> supplementation significantly increased the level of serum GUDCA in DN mice. Elevated GUDCA activated the bile acid receptor GPBAR1 in the kidney, suppressing NF-κB/NLRP3 inflammasome and TGF-β-mediated fibrosis. BCP improves renal outcomes by regulating bile acid metabolism through gut microbiota modulation, supporting its potential as a novel dietary strategy for DN.