Lactobacillus plantarum TWK10 (LP10) is a probiotic known to improve endurance exercise performance. Here, we analyze the proteomics and metagenomic changes in a LP10 supplemented mouse model. Male ICR mice were divided into two groups (n = 8) to receive by oral gavage either vehicle or of LP10 for 6 weeks. Proteins changes by LP10 treatment were subjected to the Ingenuity Pathway Analysis (IPA) to provide corroborative evidence for differential regulation of molecular and cellular functions affecting metabolic processes. Fecal samples were obtained from each mouse, and the microbial community profile analyzed by pyrosequencing of the 16S rRNA genes. Of the 880 identified proteins, 25 proteins were significantly downregulated and 44 proteins were significantly upregulated in the LP10 treated compared to vehicle group. LP10 supplementation shift in the gut microbiota to butyrate-producing members and provided from lipid oxidation since peroxisomal fatty acid oxidation in liver.