Epigallocatechin Gallate Alleviates Staphylococcal Enterotoxin A-Induced Intestinal Barrier Damage by Regulating Gut Microbiota and Inhibiting the TLR4-NF-κB/MAPKs-NLRP3 Inflammatory Cascade

Natural phytochemicals have attracted increasing attention because of their promising ability to tackle bacteriotoxin-induced public safety concerns. However, it is unclear how natural phytochemicals regulate the intestinal barrier dysfunction caused by bacteriotoxin, such as staphylococcal enterotoxin A (SEA). This study aims to illustrate the in vitro and in vivo protective mechanism of epigallocatechin gallate (EGCG) on SEA-triggered intestinal barrier damage and inflammation. Results show that EGCG alleviates intestinal barrier damage by effectively inhibiting SEA-induced intestinal permeability increase, tight junction protein and mucin loss, and intestinal cell apoptosis. EGCG also reduces intestinal inflammation by suppressing the TLR4-NF-κB/MAPKs-NLRP3 pathway. Importantly, EGCG reverses gut microbiota dysbiosis and short-chain fatty acid (SCFA) content decrease induced by SEA. It is worth noting that this study also detects the direct interaction between the phytochemical and virulence factors and finds that EGCG effectively not only inhibits the secretion of SEA but also binds with the secreted SEA to attenuate its toxicity. Taken together, EGCG mitigates SEA-induced intestinal barrier dysfunction via gut microbiota SCFA-mediated TLR4-NF-κB/MAPKs-NLRP3 inflammatory cascade inhibition. Overall, this research provides enlightening insight into the application of bacteriotoxin-targeting natural compounds in the field of food safety and human wellness.