Bifidobacterium longum subsp. infantis CCFM1445 Promotes Bone Growth in Growing Mice Via Modulating Gut Microbiota and Arginine Metabolism Pathway.

Bifidobacterium has been shown to regulate bone metabolism and maintain bone homeostasis. This study investigated the effects of Bifidobacterium longum subsp. infantis on bone growth in juvenile mice. Treatment with B. longum subsp. infantis CCFM1445 increased femur length, bone volume fraction, and cortical bone area in both female and male mice. Bone histomorphometry indicated that CCFM1445 elevated the height of the femoral growth plate, increased osteoblast numbers, and decreased osteoclast numbers. Furthermore, B. longum subsp. infantis CCFM1445 raised serum concentrations of bone formation markers, including osteoprotegerin (OPG), procollagen type I N-terminal propeptide (PINP), and bone alkaline phosphatase (BALP). Concurrently, it suppressed the levels of tartrate-resistant acid phosphatase type 5b (TRACP5b) and cross-linked N-telopeptide of type I collagen (NTX). Additionally, CCFM1445 upregulated the transcriptional network of key genes involved in osteogenesis and bone matrix synthesis. And intervention with CCFM1445 also significantly increased the relative abundance of Bifidobacterium, Alistipes, and [Eubacterium] xylanophilum group in the gut microbiota. Targeted metabolomic analysis showed that CCFM1445 modulated the arginine biosynthesis and metabolic pathway, characterized by decreased citrulline and increased levels of arginine and its downstream metabolites. Together, these results demonstrate that B. longum subsp. infantis CCFM1445 enhances bone formation, suppresses bone resorption, modulates gut microbiota composition, and influences arginine metabolism, thereby promoting longitudinal bone growth and increasing bone mass in growing mice.