Inhibitory Mechanisms of Pentagalloylglucose and Gallotannin Against Clostridium perfringens: A Transcriptomic and Metabolomic Approach with Insights into Intestinal Cell Protection

Clostridium perfringens is a common intestinal bacterium and major foodborn pathogen. In this study, we investigated the inhibitory effects and mechanisms of pentagalloylglucose (PGG) and gallotannin (GT) on C. perfringens utilizing transcriptomics and metabolomics for the first time. The results of ion concentration measurements, flow cytometry, and transmission electron microscopic tests demonstrate that PGG and GT significantly increased Mg2 and K concentration and the percentage of dead and damaged bacteria (P less than 0.05) and disrupted the microstructure of C. perfringens. Both PGG and GT significantly affected C. perfringens at the transcriptional and metabolic levels. Bioinformatics analysis revealed that PGG and GT induced cell membrane damage, amino acid restriction, energy metabolism disruption, and the inability to sense and respond to the external environment in C. perfringens. The protective effects of PGG and GT on intestinal epithelial cells were further explored using an in vitro C. perfringens-infected intestinal cell model. PGG and GT could bind to alpha toxin, significantly reduced the mRNA expression of inflammatory factors, and improved intestinal barrier function and cell viability (P less than 0.05). Compared to PGG, GT exhibited stronger inhibitory activity against C. perfringens and a greater binding ability to alpha toxin. Our results reveal the anti C. prfringens mechanism of PGG and GT and the ability to alleviate the excessive inflammatory response of intestinal epithelial cells through the inhibition of C. perfringens and alpha toxin. This study contributes to the development and application of PGG and GT in food safety.