Astragalus polysaccharide alleviates mastitis disrupted by Staphylococcus aureus infection by regulating gut microbiota and SCFAs metabolism.

Polysaccharides, key bioactive compounds derived from Chinese herbs, are increasingly recognized for their therapeutic potential in modulating gut microbiota to treat various diseases. However, their efficacy in alleviating mammary inflammation and oxidative stress and protecting the blood-milk barrier (BMB) compromised by Staphylococcus aureus (S. au) infection remains uncertain. As evidence for the gut-mammary axis grows, identifying natural prebiotic components that affect this axis is crucial. This study reveals that Astragalus polysaccharide (APS), the primary active constituent of Astragalus, effectively mitigates S. au infection in murine mammary glands, suppresses inflammatory responses, reduces oxidative stress, and restores BMB integrity. The involvement of APS in modulating gut microbiota was substantiated through gut microbial depletion experiments and fecal microbiota transplantation (FMT). Notably, APS uniquely enriched Ruminococcus bromii (R. bromii) in the gut, facilitating the metabolism of short-chain fatty acids (SCFAs), particularly acetate and butyrate, which are pivotal to APS's protective effects. Collectively, these results propose a novel therapeutic approach for the treatment and prevention of S. au-induced mastitis, leveraging APS and R. bromii as prebiotics and probiotics, respectively.