show Abstracthide AbstractXanthine 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 regulation analysis showed 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.