<i>Bifidobacterium longum</i> increases serum vitamin D metabolite levels and modulates intestinal flora to alleviate osteoporosis in mice

The elderly population is prone to osteoporosis, owing to the deterioration of the skin, liver, and kidney functions. Vitamin D (VD) supplementation has a limited effect, and VD deficiency is mostly treated with medication. Several studies have shown that the gut microbiota alters intestinal VD metabolism and that probiotic supplements can influence circulating VD levels. Therefore, in the present study, we screened a strain of <i>Bifidobacterium longum</i> FSHHK13M1 that can increase the level of VD metabolites in the fermented supernatant species <i>in vitro</i> by modeling fecal bacterial fermentation. The results showed that FSHHK13M1 intervention significantly increased the serum levels of 1,25-dihydroxy VD and osteocalcin. It activated the expression of the VDR, OPG, Wnt10b/β-catenin, and Runx2/Osterix pathways and inhibited the expression of RANKL/RANK pathway. Furthermore, there was an enhancement in the quantity of bone trabeculae and the proportion of bone volume. Concurrently, the gut microbiota in mice with osteoporosis exhibited signs of imbalance. FSHHK13M1 intervention increased the relative abundance of specific bacteria, such as <i>Faecalibaculum rodentium</i>, <i>Limosilactobacillus fermentum</i>, <i>Bifidobacterium pseudolongum</i>, and <i>Akkermansia muciniphila</i>. These results suggest that <i>B. longum</i> FSHHK13M1 alleviates retinoic acid-induced osteoporosis symptoms by modulating related genes, regulating the intestinal flora and increasing the level of active VD.IMPORTANCEOsteoporosis is a systemic metabolic disease in which the patient's bone mass decreases for a variety of reasons, and the microstructure of the bone tissue is altered, leading to an increase in bone brittleness and susceptibility to fracture. Osteoporosis is almost always present in the elderly population, and fractures from falls are an important predisposing factor for mortality risk in the elderly population. Supplementation is quite limited for them as they are not able to utilize vitamin D well due to declining liver, kidney, and skin functions. In the present study, a strain of <i>Bifidobacterium longum</i> probiotic was found to increase the levels of the active form of vitamin D and ameliorate osteoporosis. This may play an important role in preventing osteoporosis and reducing fracture risk in the elderly.