Super Astragalus polysaccharide in specific gut microbiota metabolism alleviates chronic unpredictable mild stress-induced cognitive deficits mice

Chronic stress affects intestinal microbiota. Astragaloside IV (AS), called super Astragalus polysaccharide, is a monomer component of traditional herbs Astragalus membranaceus which belongs to medicinal food homology (MFH), exerts a neuroprotection effect, but the underlying mechanism has not yet been elucidated. Intestinal flora is also involved in the biotransformation of the active ingredients of MFH species, thus affecting their physiological and pharmacological properties. In this study, we found that AS improved CUMS-induced cognitive impairment, inhibited neuroinflammation, and restored intestinal barrier damage, but the improvement was suppressed by the elimination of gut microbiota, suggesting a key regulatory role for the microbiota. The results of 16S rDNA sequencing showed that AS treatment significantly increased the relative abundance of Lactobacillus reuteri ( L. reuteri) and Bacteroides acidifaciens. Furthermore, supplementation of L. reuteri rather than Lactobacillus plantarum restored the effect of AS-supplied dysbiosis mice via inhibition of inflammatory repose and the maintenance of the intestinal epithelial barrier, indicating that dietary AS requires L. reuteri to ameliorate cognitive injury. These findings provide evidence for new therapeutic strategies to treat chronic stress and support the role of specific bacteria in the intestinal environment that metabolizes the AS.