This study describes the influence of Lactobacillus plantarum CCFM8610 on the host by employing transcriptome and untargeted metabolomics. According to the enrichment analysis, three pathways, including the complement and coagulation cascade pathway, antigen processing and presentation pathways, and protein processing in the endoplasmic reticulum pathway, were affected by L. plantarum CCFM8610 colonization. According to partial least squares-discriminant analysis, five metabolites, L-methionine, D-tryptophan, indoleacrylic acid, DL-acetylcarnitine, and L-norleucine, were identified as key metabolites in the serum. Furthermore, integrative analysis of the metabolome and transcriptome revealed connections between enriched pathways and differential metabolites, and the regulation strategy of choline by affecting gene expression was proposed. Overall, the effects of L. plantarum CCFM8610 on host health were investigated after excluding the influence of gut microbes, which provides a valuable reference for studying the potential mechanisms of the effect of probiotics on host health.