<i>Angelica sinensis</i> Polysaccharide Alleviates <i>Staphylococcus aureus</i>-Induced Mastitis by Regulating The Intestinal Flora and Gut Metabolites

The modulation of intestinal flora by various polysaccharides has been shown to mitigate disease progression. Recent research reveals a significant link between intestinal flora and the progression of mastitis. This study demonstrates that the oral administration of <i>Angelica sinensis</i> polysaccharide (ASP) reduces mammary inflammation and blood-milk barrier (BMB) damage induced by <i>Staphylococcus aureus</i> in mice, primarily through the modulation of intestinal flora. The beneficial effects of ASP were negated when antibiotics disrupted the gut microbiota in mice. Furthermore, fecal microbiota transplantation (FMT) from ASP-treated mice to recipients markedly alleviated symptoms of <i>S. aureus</i>-induced mastitis. Oral ASP not only enhances gut microbial diversity but also shifts its composition, increasing the abundance of <i>Lachnospiraceae_NK4A136</i> while reducing <i>Erysipelatoclostridium</i>. Metabolomic analysis revealed that ASP alters intestinal metabolic pathways, elevating levels of metabolites, such as tabersonine and riboflavin. Notably, tabersonine was found to ameliorate <i>S. aureus</i>-induced mastitis. These results suggest that targeting intestinal flora and metabolism through polysaccharides could serve as a promising strategy for mastitis intervention and potentially for other infectious diseases, as well.