Xanthine oxidase-lactoperoxidase system: Dose-dependent antibacterial effects and global gene expression changes in infant oral microbiota

Xanthine oxidase (XO) and lactoperoxidase (LPO) are highly abundant enzymes in milk. Their substrates, xanthine and thiocyanate, are found in elevated amounts in infant saliva, leading to a proposed interaction between milk and saliva referred to as the XO-LPO system. This system is suggested to generate reactive oxygen and nitrogen species with potential antibacterial effects. The antibacterial activity of the XO-LPO system was assessed on bacteria cultured from the oral cavities of five infants, where a reduction in bacterial growth rate was observed at 40 µg mL⁻¹ of each enzyme and with complete inhibition achieved at 200 µg mL⁻¹. Gene expression analysis showed that XO-LPO treatment led to downregulation of several reactive oxygen species-related genes, suggesting a transient bacterial stress response. The study also observed downregulation of key glycolytic enzymes, indicating that XO-LPO treatment affects bacterial metabolism at transcriptional level, suggesting a possible mechanism of action for the XO-LPO system. Collectively, these findings offer new insights into the XO-LPO system, revealing novel aspects of the interaction between lactation and microbiome influence.