Effect of a Synbiotic Combination of 2′-Fucosyllactose and Lactobacillus plantarum Hi-188 on Skeletal Growth and Gut Microbial Metabolism in Growing Mice

Background/Objectives: Early-life skeletal growth is critical for achieving optimal peak bone mass. This study aimed to investigate whether synbiotic supplementation with 2′-fucosyllactose (2′-FL) and Lactobacillus plantarum Hi-188 (LPHi-188) influences bone development in growing mice and its potential association with gut microbial modulation. Methods: Three-week-old BALB/c mice were orally supplemented with 2′-FL, LPHi-188, or their combinations at low and medium doses for 7 weeks. Bone length, microarchitecture and mechanical properties were analyzed. Serum bone turnover markers and osteogenic gene expression were analyzed by ELISA and qRT-PCR, respectively. Gut microbiota composition, and short-chain fatty acid (SCFA) production were analyzed by 16S-rRNA sequencing and GC-FID, respectively. Correlation associations among microbial taxa, SCFAs, and skeletal parameters were also assessed. Results: Medium-dose synbiotic supplementation significantly increased tibial and spine length without altering body weight or intestinal histology. Trabecular bone density and volume fraction were elevated, accompanied by reduced trabecular separation and improved mechanical strength. Serum BALP levels were increased and TRACP-5b levels were reduced, together with upregulation of osteogenesis- and matrix-related genes. Synbiotic treatment also modulated gut microbial composition, enriched SCFA-associated taxa, and significantly enhanced total and individual SCFA levels. Correlation analyses revealed selective associations among specific microbial taxa, SCFAs, and skeletal structural and molecular parameters. Conclusions: Medium doses of synbiotic supplementation were associated with improved skeletal growth and bone quality during development, alongside coordinated modulation of bone remodeling and gut microbial metabolic activity. These findings suggest its potential as a functional nutritional strategy for supporting early bone health.