Modulating the intestinal flora involves the effect of Atractylodis macrocephalae Rhizoma polysaccharide on spleen...

Atractylodis macrocephalae Rhizoma (AM), a widely used Chinese herb for treating spleen deficiency diarrhea (SDD), is rich in polysaccharides. However, the precise mechanism underlying the antidiarrheal effects of Atractylodis macrocephalae Rhizoma polysaccharide (AMP) remains unclear. In this study, AMP, with a molecular weight of 69 kDa, is isolated from AM and consists of Glc, Gal, and Ara in a molar ratio of 84.16:6.51:9.33. FTIR and NMR analyses indicate that AMP features a linear backbone of →4,6)-α-D-Glcp-(1→ with branches of →3)-β-D-Glcp-(1→, terminating in →2,4)-β-D-Galp-(1→. Animal models of SDD induced by Folium sennae demonstrate that AMP alleviates diarrhea symptoms, mitigates colon damage, and enhances spleen index, thymus index, and the expression of CD4⁺CD25⁺Foxp3⁺Treg cells. Further, the potential mechanisms for AMP's antidiarrheal action are explored through the comprehensive approach integrating intestinal flora, polysaccharide utilization loci, short-chain fatty acids (SCFAs), and metabolomics. AMP reduces the abundance of pathogenic c_Clostridia while promoting beneficial o_Bacteroidales and f_Muribaculaceae, influencing SCFAs production via its strong binding affinities with SusD, GH2, and GH43. This modulation is linked to alterations in linoleic acid metabolism, alpha-linolenic acid metabolism, and primary bile acid biosynthesis. In conclusion, AMP demonstrates significant potential as a therapeutic agent for SDD.