Meiyu Yuan, Yihong Li, Zixuan Zhou, Wanting Dai, Xian Cui, Shuang Bi, Xiaoxiao Song
ABSTRACT Selenium (Se) exists in various chemical forms, including inorganic Se, organic Se, and Se nanoparticles (SeNPs). However, the mechanisms underlying the interaction between Se and gut microbiota remain unclear. This study systematically evaluated the effects of different polysaccharide‐stabilized Se nanoparticles (PS‐SeNPs) using an in vitro colonic fermentation model. The results indicate that the molecular properties of polysaccharides (PS) are key factors influencing the gut microbiota‐modulating effects of PS‐SeNPs. Specifically, high molecular weight and positively charged PS enhance the microbial utilization of SeNPs. Chitosan‐based Se nanoparticles (CS‐Se) and chitosan quaternary ammonium salt‐based Se nanoparticles (HACC‐Se) can specifically enrich beneficial bacterial communities, such as Lactobacillus and Bacteroidales , which possess both acid production and Se metabolism capabilities. This enrichment significantly promotes the accumulation of short‐chain fatty acids and the generation of selenocystine (SeCys 2 ) and Se‐Methylselenocysteine (MeSeCys). Metabolomics analysis further showed significant activation of amino acid biosynthetic pathways. Chitosan oligosaccharide‐based Se nanoparticles (COS‐Se) and carboxymethyl cellulose‐based Se nanoparticles (CMC9‐Se) can enrich beneficial microorganisms. However, their bioavailability and microbial assimilation efficiency remain relatively limited. The H 2 SeO 3 group significantly promoted the proliferation of microorganisms such as Enterobacteriaceae, Escherichia‐Shigella, and Klebsiella . Our findings could improve understanding of the interaction between Se and gut microbiota.