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

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.

Effect of probiotics on postmenopausal bone health: a preclinical meta-analysis

“…To further investigate the effect of probiotic treatment on bone formation, we examined the data from twenty-two selected articles that reported serum bone formation markers levels. Of these, six studies reported on serum osteocalcin (16,25,31,33,34,42) , seven studies on serum Ca (16,25,27,30,31,41,42) and six studies on serum ALP (27,29,30,34,40,41) . Pooled effect analysis was carried out using random effects model due to sufficient heterogeneity among studies.…”

“…However, due to high heterogeneity, meta-analysis could not be performed on Bifidobacterium . Similarly, serum ALP was reported in six articles using Lactobacillus (27,29,30,34,40,41) and only one article using Bifidobacterium (30) , preventing a comparison of the two species.…”

“…A total of 238 ovariectomised rats were used; 95 in control and 143 in experimental group. Among the eleven studies on mice, four studies used Balb/c mice (35)(36)(37)(38) , one used Institute of Cancer Research (ICR) mice (39) , five used C57Bl/6 mice (16,(40)(41)(42)(43) and one used ddy mouse strain (44) . A total of 215 ovariectomised mice were used, of which 88 were in control group and 127 in experimental group.…”

Optimization, fractional characterization, and antioxidant potential of exopolysaccharides from Levilactobacillus brevis NCCP 963 isolated from “kanji”

“…4 Many benecial effects including antioxidant, antimicrobial, anti-inammatory, antiviral, immunomodulatory, antitumor, and cholesterol adsorption activities of LAB-derived EPSs have been reported. 3,5,6 Furthermore, LAB-derived EPSs are used as syneresis-lowering agents, texturizers, viscosiers, and emulsi-ers, and also exhibited lm-making capabilities and pseudoplastic rheological behavior in the food industry. 7 Literature indicates that there are a number of factors such as carbon and nitrogen sources, pH of the culture media, growth medium, incubation temperature, enzyme production, and process conditions that affect the EPS production from LAB.…”

“…4 Many beneficial effects including antioxidant, antimicrobial, anti-inflammatory, antiviral, immunomodulatory, antitumor, and cholesterol adsorption activities of LAB-derived EPSs have been reported. 3,5,6 Furthermore, LAB-derived EPSs are used as syneresis-lowering agents, texturizers, viscosifiers, and emulsifiers, and also exhibited film-making capabilities and pseudoplastic rheological behavior in the food industry. 7…”