Inonotus obliquus polysaccharides improve hyperlipidemia with respect to lipid synthesis and intestinal flora modulation.

Chronic high-fat diet can lead to fatty liver metabolism, hyperlipidemia disorders, and other diseases. Polysaccharides are natural lipid-lowering agents. Nevertheless, the lipid-lowering mechanism of Inonotus obliquus polysaccharides (IOP) needs to be clarified. This study extracted polysaccharides from Inonotus obliquus, and their physicochemical properties and hypolipidemic activity were investigated. Structural characterization by scanning electron microscopy and Fourier transform infrared spectroscopy indicated that IOP displayed functional groups and morphological features typical of polysaccharides. The primary monosaccharides were mannose, ribose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose, xylose, and fucose. The molecular weight of IOP was 9.637 kDa and belonged to the α-pyranose configuration. In high-fat diet mice, IOP administration had significant regulatory effects on multiple metabolic parameters. It improved serum lipid profiles and attenuated pro-inflammatory cytokine expression, effectively reducing lipid deposition in both hepatic tissues and adipocytes. Molecular analyses revealed its capacity to downregulate key genes associated with hepatic lipogenesis. The intervention exhibited gut microbiota-modulating properties, evidenced by enhanced production of short-chain fatty acids and structural optimization of microbial communities. Notably, administration of IOP induced significant changes in the composition of the intestinal flora, particularly increasing the abundance of Akkermansia, norank_f_Muribaculaceae, Lactobacillus, Ruminococcac, Lachnospiraceae_UCG-006 and Prevotellaceae_UCG- 001 and reduced abundance of Blautia, Desulfovibrio and norank_f__ Lachnospiraceae. These results suggest that IOPs are natural polysaccharides, which may serve as potential functional food ingredients for preventing or treating hyperlipidemia.