Effects of Menaquinone-7 on the Bone Health of Growing Rats under Calcium Restriction: New Insights from Microbiome-Metabolomics

Insufficient calcium intake during growth is a global public health concern. The aim of this study was to investigate the effects of dietary menaquinone-7 (MK-7) on bone accrual in growing Sprague-Dawley rats under calcium restriction. Following 13 weeks of treatment, various bone quality parameters, including microarchitecture, were measured. Fecal and cecal samples were subjected to microbiome (16S rRNA gene sequencing) analyses, while metabolomics analysis of the cecum and humerus samples was analyzed based on UHPLC-Q/TOF-MS. We found that calcium deficiency diminished the richness of the microbiome and disrupted microbiome composition, accompanied by an elevation in the relative abundance of Parasutterella. Furthermore, calcium insufficiency escalated the level of isovaleric acid and modified the metabolic profiles. MK-7 supplementation significantly increased the cortical thickness, cortical bone area, and the calcium content of the femur. Apart from improving bone calcium deposition and diminishing bone resorption, the mechanisms underlying the beneficial effects of MK on bone quality also involve the modulation of the host's metabolic pathways and the composition of gut microbiota. The gut-bone axis holds promise as an efficacious target for ameliorating calcium deficiency in children's bone quality, and MK-7 is a promising dietary supplement from this perspective.

Automated summary

The study aimed to investigate the effects of dietary menaquinone-7 (MK-7) on bone accrual in growing Sprague-Dawley rats under calcium restriction. It was found that calcium deficiency reduced microbiome richness, disrupted microbiome composition, and increased the relative abundance of Parasutterella. Additionally, calcium insufficiency affected metabolite levels and metabolic profiles. MK-7 supplementation improved bone density, calcium content, and bone quality through modulation of metabolic pathways and gut microbiota composition. The gut-bone axis and MK-7 supplementation show promise in ameliorating calcium deficiency in children's bone quality.