Prebiotic Effects of Lycium barbarum Polysaccharides on Gut Microbiota and Short‐Chain Fatty Acids Production in Wilson's Disease: An In Vitro Fermentation Study

ABSTRACT Wilson's disease (WD) is a rare autosomal recessive disorder characterized by impaired copper metabolism and progressive multi‐organ damage. Emerging evidence suggests that gut microbiota dysbiosis and reduced microbial fermentation capacity may contribute to the progression of liver diseases. However, whether the gut microbiota can serve as a therapeutic target in WD remains unclear. This study aimed to investigate the modulatory effects of Lycium barbarum polysaccharides (LBPs), a bioactive component of the traditional Chinese medicine Gan‐Dou‐Fu‐Mu decoction, on gut microbiota composition and short‐chain fatty acids (SCFAs) production in WD, and to explore their potential as microbiota‐targeted prebiotic interventions. WD‐associated microbiota exhibited decreased microbial diversity and significantly lower SCFAs production, particularly acetic acid and total SCFAs, compared to healthy controls. LBPs supplementation significantly increased the relative abundances of beneficial genera, including Lactobacillus , Lacticaseibacillus , and Paraeggerthella , as well as SCFAs‐producing species such as Bacteroides fragilis and Lactobacillus delbrueckii . Notably, LBPs markedly enhanced acetic acid and total SCFA concentrations in WD microbiota, outperforming the standard treatment agent penicillamine. These findings highlight the promising prebiotic potential of LBPs and support their application as a novel microbiota‐targeted adjunctive therapy for WD.