Therapeutic potential of oyster peptides against Staphylococcus aureus-induced mastitis via attenuating inflammation, mitochondrial dysfunction and modulating gut microbiota.

Staphylococcus aureus (S. aureus)-induced mastitis represents a significant challenge in dairy production. Oyster peptides (OP), bioactive compounds derived from oysters, exhibit considerable therapeutic value in treating various diseases due to their antibacterial and anti-inflammatory properties. Nevertheless, their role in alleviating mastitis and protecting the blood-milk barrier (BMB) from S. aureus infection remains underexplored. This study reveals that OP effectively attenuates S. aureus-induced inflammation, reduces oxidative stress, and maintains BMB integrity by preserving tight junction protein expression. Mechanistic studies indicate that OP suppresses the S. aureus-induced over-activation of the TLR2-NF-κB and IP3R1/GRP75/VDAC1 signaling pathways, thereby mitigating inflammation and mitochondrial damage. In addition, 16S rDNA sequencing of the gut microbiota demonstrates that OP modulates microbial composition, enhancing the abundance of beneficial bacteria such as Bacteroides acidifaciens while downregulating harmful bacterial populations. Metabolomic analysis also indicates that OP affects intestinal metabolic pathways, increasing the levels of metabolites like 13-Hotre and stearidonic acid. In conclusion, these findings suggest that OP holds promise as a therapeutic agent for the treatment and prevention of S. aureus-induced mastitis.