Nucleotides　(NTs)　are　extremely　important　low-molecular-weight　compounds　in　organisms,　and　play　an　important　role　in　cell　metabolism,　energy　and　functional　regulation.　Our　previous　study　found　that　NTs　regulated　the　intestinal　flora　of　rapid-aging　mice　(senescence-accelerated　mouse　prone-8,　SAMP-8)　and　played　a　significant　role　in　promoting　the　growth　of　Lactobacillus　casei.　However,　the　mechanism　by　which　NTs　promote　the　antagonization　of　intestinal　pathogens　by　probiotics　remains　unclear.　Therefore,　we　explored　the　mechanism　by　which　NTs　promote　the　antagonization　of　intestinal　pathogens　by　L.　casei　via　in　vitro　coculture.　The　results　showed　that　NTs　promoted　the　growth　of　L.　casei,　while　negatively　affecting　Salmonella　enterica.　NTs　increased　the　antagonism　of　S.　enterica　biofilm　formation,　swimming,　swarming,　and　secretion　of　siderophore　by　L.　casei.　This　antagonism　was　probably　due　to　NTs　activating　the　LuxS　protein　in　L.　casei,　which　closely　combines　with　NTs,　promoting　the　secretion　of　AI-2　signaling　molecule　and　triggering　the　expression　of　genes　related　to　the　quorum　sensing　system,　enabling　L.　casei　to　produce　specific　physiological　activities.　This　study　provides　a　theoretical　basis　for　exploring　using　NTs　as　potential　prebiotics.　©　2023　The　Authors