Gut microbiota and metabolic profiles alteration during in vitro fecal fermentation of an immunostimulatory polysaccharide from Astragalus membranaceus

Astragalus membranaceus polysaccharides have shown promising immune activities; however, their interactions with gut microbiota and metabolites remain largely unclear. This study utilized an in vitro human fecal fermentation model to examine the degradation properties, modulation of intestinal flora and metabolites, and alterations of immune activity by an immunostimulatory AMP fraction, AMP40. After 48 h-fermentation, total sugar content and pH decreased, while acetic acid production increased significantly due to utilization of AMP40. Additionally, AMP40 stimulated the proliferation of beneficial gut bacteria, particularly Bifidobacterium and Bacteroides, while inhibiting potentially harmful bacteria, Peptoclostridium and Bilophila. Bioinformatics analysis suggested that the L-histidine metabolism may be the key pathway mediating AMP40's health-regulating effects, with Bifidobacterium as the major contributing genus. Fermented AMP40 further enhanced the immunostimulatory activity on RAW264.7 macrophages. In summary, AMP40 harbors high potential to be a novel prebiotic strategy for enhancing host immunity via modulation of gut microbiota and their metabolites.