Extraction Process Optimization, Structural Characteristics and Gut Microbiota Metabolism Regulatory Effect of...

Edible fungal polysaccharides have been recognized as low-toxic natural candidates for tumor adjuvant therapy by regulating gut microbiota and host metabolism. This study aimed to prepare an S. luteus alkali-extracted (pH = 9) polysaccharide (SLP9) via optimized extraction and systematically elucidate the anti-tumor effects based on polysaccharide structure, genus-level gut microbiota and fecal metabolomics. Structural characterization via high-performance gel permeation chromatography (HPGPC), gas chromatography-mass spectrometry (GC-MS) and Fourier-transform infrared spectroscopy (FTIR) verified that SLP9 possessed abundant β-glycosidic linkages with a Xyl:Man:Glc:Gal molar ratio of 0.52:1.00:0.81:0.57 and an average molecular weight of approximately 1.58 × 10⁷ Da. An in vivo anti-tumor experiment revealed that high-dose SLP9 exhibited obvious tumor inhibition with an inhibitory rate of 40.28% via restoring microbial diversity and selectively enriching the beneficial genus Lactobacillus, which might be relevant with activating three top significant KEGG pathways tropane, piperidine and pyridine alkaloid biosynthesis, arginine biosynthesis, alkaloid biosynthesis from ornithine, lysine and nicotinic acid. Collectively, this study systematically revealed the intrinsic correlations between the SLP9 extraction process, structural characteristics, targeted regulation of intestinal microbial metabolism and anti-tumor activity. These findings provide comprehensive theoretical support for using SLP9 as a new microecological regulator for tumor adjuvant therapy.