Gut microbiota remodeling by Astragalus membranaceus stems and leaves correlates dual modulation of arachidonic acid and tryptophan metabolism to counteract perinatal stress-induced hemometabolic dysregulation in sows

Perinatal stress (PS) commonly occurring in high-yielding sows has gradually become a factor threatening the reproductive and immunoreactive performances by impairing their fecundity. Despite the Astragalus membranaceus, a herb native to northern China, has been applied to relieve PS, it is still unclear whether its aerial parts, i.e., Astragalus membranaceus stems and leaves (AMSL), protects against reproductive damage induced by PS in sows and how it works. Here, we aims to evaluate the novel roles of AMSL in alleviating PS-induced reproductive disorders in sows (n = 45) and their offsprings (n = 45). Amplicon-based microbiota analysis revealed that maternal dietary supplementation of AMSL significantly induced affluent Prevotella, Limosilactobacillus, Rikenellaceae_RC9_gut_group, and Clostridium_sensu_sticto_1 in perinatal sows and was correlated with accelerated maturation of gut microbiota in preweaning piglets. Untargeted metabolomics were used to profile serum and fecal metabolites, and serum arachidonic acid (AA)-related metabolites were markedly diminished on the day of farrowing and from neonatal piglets at birth post AMSL administration in sows. Pearson correlation analyses indicated that enriched indole-related metabolites and fewer kynurenine-related metabolites were strongly positively correlated with these four bacteria. Then, fecal microbiota transplantation (FMT) in pregnant mice were conducted to illustrate whether the protective role of AMSL is mediated by remodeling gut microbiota. PS and immunosuppressive symptoms were both largely ameliorated in mice that had received fecal bacteria of sows pretreated with AMSL. These results support the notion that the beneficial effects of AMSL were primarily achieved via gut microbiota modulation, which related to improved tryptophan metabolism and inhibited the excessive synthesis of AA in blood circulation. Our findings provide new insights into the potential application of AMSL as a sustainable feed additive.