ABSTRACT Atractylodes macrocephala polysaccharides (AMPs) are known to exert metabolic regulatory and immunomodulatory activities, yet their protective effects across multiple organs in diabetes and the mechanisms involving gut‐organ crosstalk have not been fully elucidated. In this study, we investigated the multi‐organ benefits of AMPs in high‐fat diet/streptozotocin‐induced diabetic male C57BL/6 mice, with a particular focus on the gut microbiota‐intestinal barrier‐metabolite axis. Diabetic mice were treated with saline, losartan (30 mg/kg), metformin (100 mg/kg), or AMPs (100 or 300 mg/kg) for 8 weeks. Metabolic parameters, renal dysfunction, and hepatic injury were evaluated by measuring blood glucose, creatinine, proteinuria, and serum ALT/AST levels, together with histopathological examination. Inflammatory and fibrotic responses were assessed using qPCR, Western blotting, and immunostaining, while colonic barrier integrity was determined by the expression of the tight junction proteins ZO‐1 and occludin. In addition, gut microbial composition was analyzed by 16S rRNA sequencing, and cecal metabolic profiles were characterized using LC–MS‐based metabolomics. AMP treatment markedly improved glucose homeostasis and attenuated kidney and liver injury, as evidenced by reduced creatinine, proteinuria, ALT/AST levels, and tissue damage. These benefits were accompanied by decreased macrophage infiltration and suppression of inflammasome activation and fibrotic signaling. AMPs also alleviated colonic injury and restored intestinal barrier‐associated proteins. Furthermore, AMP administration improved microbial diversity and altered the metabolic profile, with 134 differential metabolites identified, including several unsaturated fatty acids. Collectively, these findings suggest that AMPs protect the gut‐liver‐kidney axis, at least in part, by remodeling the gut microbiota, strengthening intestinal barrier function, and partially correcting disturbances in unsaturated fatty acid metabolism, highlighting their potential as an adjunctive therapeutic strategy for diabetic kidney disease and fatty liver disease.
Wu et al. (Mon,) studied this question.