Low molecular weight chitosan selenium nanoparticles (LCS-SeNPs), a biologically active compound derived from selenium polysaccharides, have demonstrated potential in addressing obesity. However, the mechanism through which LCS-SeNPs alleviate high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) remains unclear. Our results elucidated that LCS-SeNPs significantly inhibited fat accumulation and markedly improved the intestinal barrier by increasing mucus secretion from goblet cells. Moreover, LCS-SeNPs reshaped intestinal flora composition by increasing the abundance of mucus-associated microbiota (Bifidobacterium, Akkermansia, and Muribaculaceae_unclassified) and decreasing the abundance of obesity-contributed bacterium (Anaerotruncus, Lachnoclostridium, and Proteus). The modulation of intestinal microbiota by LCS-SeNPs influenced several metabolic pathways, including bile acid secretion, purine metabolites, and tryptophan derivation. Meanwhile, glycocholic acid and tauro-beta-muricholic acid were significantly reduced in the LCS-SeNP group. Our study suggests the crucial role of intestinal microbiota composition and metabolism, providing a new theoretical foundation for utilizing selenium polysaccharides in the intervention of HFD-induced NAFLD.

Background: The water-soluble Grifola frondosa polysaccharides (GFPs) are the primary bioactive component of the edible and medicinal fungus Grifola frondosa. However, the digestive behavior of GFPs in the human gastrointestinal (GI) tract and their subsequent interaction with gut microbiota (GM) to exert health effects remain unclear. Methods: In this study, GFPs were extracted based on a traditional hot water decoction. An in vitro simulated GI digestion model and a human fecal microbiota fermentation model were established to systematically investigate the digestive stability of GFPs, GM modulation, and metabolite changes. Results: Results showed that GFPs remained structurally stable during in vitro oral, gastric, and small intestinal digestion, allowing them to reach the colon intact for microbial fermentation. During colonic fermentation, GFPs were efficiently degraded by GM, and significantly increased the relative abundance of beneficial bacteria such as Akkermansia, Bacteroides, Parabacteroides, and Lactobacillus while reducing the abundance of pathogenic Escherichia-Shigella. Meanwhile, GFPs enriched metabolites beneficial for intestinal health, among which γ-aminobutyric acid (GABA) was the most significantly upregulated. Single-strain fermentation confirmed that Lactobacillus (L. plantarum) was the core GABA-producing genus. Conclusions: This study highlights the potential of GFPs as prebiotics for GM modulation, expands the understanding of the health-promoting effects of fungal polysaccharides, and provides a theoretical basis for the development of GFP-based functional foods.

The therapeutic landscape for neurodegenerative diseases (NDs), including Alzheimer’s and Parkinson’s disease, remains challenging due to their complex, multifactorial pathogenesis and the limited efficacy of conventional therapies that primarily offer symptomatic relief. The emergence of nanozymes, nanomaterials with intrinsic enzyme-mimicking activities, presents a promising opportunity for multi-targeted intervention. This review comprehensively explores the rational design and therapeutic mechanisms of nanozymes in combating core pathological features of NDs, such as oxidative stress, protein aggregation, and neuroinflammation. We critically assess their remarkable ability to cross the blood–brain barrier and execute synergistic functions, including reactive oxygen species scavenging, misfolded protein degradation, and modulation of microglial activation. Furthermore, we provide a detailed analysis of the application and efficacy of nanozymes across major NDs, alongside a discussion on pharmacokinetics, biosafety, and prevailing challenges. By delineating the structure-enzyme-mimicking activity relationships and cellular-level mechanisms, this review aims to establish a foundational framework for the future development of nanozyme-based neuroprotective strategies, supporting ongoing efforts toward disease-modifying interventions for NDs.