Effect of on Caries Prevention and the Oral-Gut Microbiome In Vivo.

While has shown promise against cariogenic pathogens, its in vivo effects on caries prevention remain unexplored. This study used a rat model to investigate the effect of early-life oral inoculation on oral and gut microbiomes, host immune responses, and serum metabolites. Forty 14-day Sprague-Dawley rat pups were randomly allocated into 5 groups: (1) blank control, (2) colonization alone, (3) and co-colonization, (4) precolonization before and exposure, and (5) 2-wk treatment of after and exposure. Dynamic colonization of , , and in saliva and plaque was assessed using a culture-dependent method. Saliva, plaque, and fecal microbiomes were assessed using 16S ribosomal RNA gene sequencing. Caries scoring was performed using Keyes' scoring system and microcomputed tomography. Serum metabolite and immune markers were assessed through liquid chromatography tandem mass spectrometry untargeted metabolomics and multiplex immune profiling. We found that 3-d inoculation established stable colonization in the oral cavity of young rats. Inoculation timing of was critical for caries prevention. precolonization significantly reduced caries lesions compared with the and group, whereas 2 wk of postexposure treatment did not demonstrate a protective effect. precolonization led to distinct microbial shifts in saliva, plaque, and gut microbiomes, with an increased abundance of beneficial bacteria, such as , , , and , and a decrease in preinoculation also influenced metabolic profiles, with 1 metabolite upregulated and 24 downregulated, although immune marker differences were minimal. In conclusion, oral colonization before host exposure to oral cariogenic pathogens effectively reduced caries and modulated the profile of oral and gut microbiomes and serum metabolic profile.