Anti-Osteoporotic Effect of Lactobacillus brevis AR281 in an Ovariectomized Mouse Model Mediated by Inhibition of Osteoclast Differentiation

SIMPLE SUMMARY: Osteoporosis-related fractures are among the most common complications found in postmenopausal adults, which results in considerable economic impacts. Most treatments for osteoporosis increase bone formation or decrease bone resorption. While estrogen replacement therapy may be the gold standard for the treatment of osteoporosis, it also carries an increased risk of cardiac events and strokes in women. Thus, it is important to seek a safe and effective treatment method. Gut homeostasis is demonstrably linked to bone health. Probiotics are widely known to modulate gut microbiota, but with large strain differences. Our findings showed a strain of Lactobacillus brevis AR281 with an anti-osteoporotic property in ovariectomized mice, which may provide a new way to prevent osteoporosis. ABSTRACT: Osteoporosis is a global disease characterized by weakened bone microarchitecture, leading to osteoporotic fractures. Estrogen replacement therapy is the traditional treatment for osteoporosis but carries with it an increased risk of cardiac events. In search of a safe and effective treatment, we used Lactobacillus brevis AR281, which has anti-inflammatory properties, to conduct a 7-week experiment, investigating its inhibitory effects on osteoporosis in an ovariectomized (ovx) mouse model. The results demonstrated that AR281 significantly improved bone microarchitecture and biomechanical strength in ovx mice by attenuating bone resorption. AR281 significantly decreased the critical osteoclast activator, the ratio of the receptor activator for nuclear factor kappa B (NF-κB) ligand (RANKL) to osteoprotegerin, and pro-inflammatory osteoclastogenic mediators, such as IL-1, IL-6, and IL-17, which can increase the RANKL expression. Moreover, AR281 modulated intestinal microbiota in ovx mice increased the abundance of Akkermansia, which is responsible for the improvement of gut epithelial barrier integrity. In an in vitro trial, AR281 suppressed the number of osteoclasts differentiated from the osteoclast precursor RAW264.7 cells caused by RANKL through the tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6)/NF-κB/nuclear factor of activated T cells c1 (NFATc1) pathway. Therefore, AR281 may be a natural alternative for combating osteoporosis.