Tupistra chinensis polysaccharides remitted intestinal inflammation induced by LPS via regulating gut microbiota

Natural products are increasingly regarded as alternatives to antibiotics due to rising concerns about antimicrobial resistance (AMR). As a result, we investigated the therapeutic effects of Tupistra chinensis (TC) polysaccharides in lipopolysaccharide (LPS)-challenged mice. Thirty ICR mice were divided into three groups: control (DB), LPS- LPS-challenged (LB), and TC-treated (KB). The KB group received oral TC polysaccharides (1 g/kg/day) for 14 days, followed by the LPS challenge. Histopathological analysis revealed that TC polysaccharides restored intestinal mucosal integrity and splenic architecture to near-normal levels following LPS-induced damage. High-throughput 16 s rRNA sequencing demonstrated that LPS significantly (p < 0.05) reduced alpha(α)-diversity (Shannon and Pielou indices), with distinct clustering observed between the LPS- and TC-treated groups regarding beta(β)-diversity. At the phylum level, beneficial Verrucomicrobiota, Firmicutes, and Campylobacterota increased while pathogenic Proteobacteria decreased in the TC group. At the genus level, Paramuribaculum, Prevotella, Alloprevotella, and Duncaniella (anti-inflammatory) were elevated in the TC-treated group, while LPS-induced pathogens (Bacteroides_H, UBA 3263, and Erysipelatoclostridium) were diminished. LeFSe analysis indicated TC-associated taxa, including Campylobacterota, Helicobacter-D, and COE 1, linked to inflammation resolution. Regarding metabolic pathways, TC upregulated vitamin K2 biosynthesis pathways and energy metabolism, mitigating oxidative stress, while LPS increased pathways related to the degradation of amino acids (L-arginine, L-threonine), which TC counteracted. In conclusion, the restoration of gut microbiota diversity and metabolic homeostasis underscores TC's potential as an antibiotic alternative for treating enteritis through microbiota-targeted mechanisms.