Dendrobium officinale polysaccharide–spermidine hydrogels attenuate high-fat diet-induced obesity by increasing Bifidobacterium

The synergistic anti-aging effects of Dendrobium officinale polysaccharides (DOP) and spermidine (Spd) via metabolic regulation have been reported in Caenorhabditis elegans . Notably, DOP and Spd spontaneously formed a DOP–Spd hydrogel (DS) at a DOP:Spd ratio of 18:2. However, whether and how DS influences the gut microbiota and host metabolism remains unclear. In this study, an in vitro colonic fermentation model was used to investigate the effects of DOP and DS on gut microbial composition and metabolite profiles. Compared to the control group, DS significantly promoted the growth of Bifidobacterium and Lactobacillus by 6.69-fold and 3.75-fold, respectively. Compared with DOP alone, DS showed greater enrichment of Prevotella _2 (+111.06%), short-chain fatty acids (SCFAs; +34.16%), NAD + (27.83-fold), and adenosine (2.89-fold). PICRUSt-based KEGG functional prediction revealed downregulation of lipid metabolism, accompanied by a relative increase in amino acid and nucleotide metabolism pathways. To verify these effects in vivo , high-fat-diet (HFD)–induced metabolic disorder mice were used. Compared with the model group, DS treatment significantly reduced epididymal (−18.66%) and subcutaneous (−26.46%) fat indices, improved glucose tolerance, and enhanced hepatic antioxidant capacity with CAT activity and GSH level increasing by 48.53% and 77.43%, respectively. Moreover, DS reshaped the gut microbiota increasing Lactobacillus and Bifidobacterium while suppressing Helicobacter , elevated fecal SCFA levels, and increased metabolites (α-linolenic acid, nicotinic acid) involved in unsaturated fatty acid biosynthesis and purine metabolism. Spearman correlation analysis showed that Bifidobacterium was associated with the largest number of metabolites and biochemical indicators, being significantly positively correlated with hepatic GSH, propionic acid, and adenosine, and significantly negatively correlated with hepatic TG. In conclusion, DS ameliorates lipid metabolic disturbances and oxidative stress by modulation of the gut microbiota and key metabolites (SCFAs, nicotinic acid, NAD + ), highlighting its potential as a functional food ingredient for supporting glucose and lipid metabolic health.