The probiotic Bifidobacterium longum subsp. longum 35624® (B. longum 35624®), with its surface exopolysaccharide (EPS624), has previously been demonstrated to induce immunoregulatory responses in the host and may, therefore, be a novel approach to prevent bone loss in inflammatory conditions such as post-menopausal osteoporosis (PMO). The aim of this study was to investigate the effect of EPS624 on osteoclast and osteoblast differentiation and to assess the potential of B. longum 35624® to prevent bone loss in vivo. In vitro cell assays were used to assess the impact of EPS624 on osteoclast and osteoblast differentiation. The potential of two probiotic B. longum 35624® strains, including an EPS-deficient strain, for preventing ovariectomy (Ovx)-induced bone loss was assessed in a murine model. EPS624 prevented osteoclast formation from murine bone marrow precursors under both normal and TNFα-induced inflammatory conditions and modestly increased mineralized matrix deposition in osteogenic cell cultures. However, in the presence of an anti-TLR2 blocking antibody, or in MyD88^−/− osteoclast precursors, the inhibitory effect of EPS624 on osteoclast formation was diminished or completely prevented, respectively. Moreover, EPS624 induced IL-10 production in osteoclast precursors in a TLR2-dependent manner, although IL-10 was dispensable in the EPS624-mediated inhibition of osteoclast formation. In addition, EPS624-producing B. longum 35624® partially prevented bone loss in Ovx mice when administered by oral gavage. This study introduced EPS624 as a potential anti-resorptive therapy, although optimal in vivo delivery of the probiotic strain for treating low-grade inflammatory diseases such as PMO remains to be determined.

益生菌长双歧杆菌亚种。longum 35624® ( B. longum 35624® ) 及其表面胞外多糖 (EPS624) 之前已被证明可在宿主体内诱导免疫调节反应，因此可能是一种预防炎症条件下骨质流失的新方法，例如绝经期骨质疏松症（PMO）。本研究的目的是研究 EPS624 对破骨细胞和成骨细胞分化的影响，并评估长双歧杆菌 35624®预防体内骨质流失的潜力。体外细胞试验用于评估 EPS624 对破骨细胞和成骨细胞分化的影响。两种益生菌的潜力B. longum 35624®在小鼠模型中评估了用于预防卵巢切除术 (Ovx) 引起的骨质流失的菌株，包括 EPS 缺陷菌株。EPS624 在正常和 TNFα 诱导的炎症条件下阻止鼠骨髓前体形成破骨细胞，并适度增加成骨细胞培养物中的矿化基质沉积。然而，在抗 TLR2 阻断抗体存在下，或在 MyD88 ^-/- 破骨细胞前体中，EPS624 对破骨细胞形成的抑制作用分别减弱或完全阻止。此外，EPS624 以 TLR2 依赖性方式诱导破骨细胞前体中 IL-10 的产生，尽管 IL-10 在 EPS624 介导的破骨细胞形成抑制中是可有可无的。此外，产生 EPS624 的B. longum 35624®当通过口服管饲给药时，部分预防了 Ovx 小鼠的骨质流失。这项研究将 EPS624 介绍为一种潜在的抗再吸收疗法，尽管用于治疗低度炎症性疾病（如 PMO）的益生菌菌株的最佳体内递送仍有待确定。