Background

Osteoporosis (OP) is a systemic metabolic bone disease characterized by decreased bone mass and destruction of bone microstructure, which tends to result in enhanced bone fragility and related fractures. The postmenopausal osteoporosis (PMOP) has a relatively high proportion, and numerous studies reveal that estrogen-deficiency is related to the imbalance of gut microbiota (GM), impaired intestinal mucosal barrier function and enhanced inflammatory reactivity. However, the underlying mechanisms remain unclear and the existing interventions are also scarce.

Methods

In this study, we established a mouse model induced by ovariectomy (OVX) and conducted fecal microbiota transplantation (FMT) by gavage every day for 8 weeks. Subsequently, the bone mass and microarchitecture of mice were evaluated by the micro computed tomography (Micro-CT). The intestinal permeability, pro-osteoclastogenic cytokines expression, osteogenic and osteoclastic activities were detected by the immunohistological analysis, histological examination, enzyme-linked immunosorbent assay (ELISA) and western blot analysis accordingly. Additionally, the composition and abundance of GM were assessed by 16S rRNA sequencing and the fecal short chain fatty acids (SCFAs) level was measured by metabolomics.

Results

Our results demonstrated that FMT inhibited the excessive osteoclastogenesis and prevented the OVX-induced bone loss. Specifically, compared with the OVX group, FMT enhanced the expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin) and suppressed the release of pro-osteoclastogenic cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)). Furthermore, FMT also optimized the composition and abundance of GM, and increased the fecal SCFAs level (mainly acetic acid and propionic acid).

Conclusions

Collectively, based on GM-bone axis, FMT prevented the OVX-induced bone loss by correcting the imbalance of GM, improving the SCFAs level, optimizing the intestinal permeability and suppressing the release of pro-osteoclastogenic cytokines, which may be an alternative option to serve as a promising candidate for the prevention and treatment of PMOP in the future.

The translational potential of this article

This study indicates the ingenious involvement of GM-bone axis in PMOP and the role of FMT in reshaping the status of GM and ameliorating the bone loss in OVX-induced mice. FMT might serve as a promising candidate for the prevention and treatment of PMOP in the future.

中文翻译：

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粪便微生物群移植通过调节肠道微生物群和代谢功能改善卵巢切除术引起的骨质疏松小鼠的骨质流失

背景

骨质疏松症（osteoporosis，OP）是一种以骨量减少和骨微结构破坏为特征的全身代谢性骨病，往往导致骨脆性增加和相关骨折。绝经后骨质疏松症（PMOP）比例较高，大量研究表明雌激素缺乏与肠道菌群（GM）失衡、肠黏膜屏障功能受损和炎症反应增强有关。然而，潜在的机制仍不清楚，现有的干预措施也很少。

方法

在这项研究中，我们建立了卵巢切除术（OVX）诱导的小鼠模型，并每天通过管饲法进行粪便微生物群移植（FMT），持续 8 周。随后，通过微型计算机断层扫描（Micro-CT）评估小鼠的骨量和微结构。通过免疫组织学分析、组织学检查、酶联免疫吸附试验（ELISA）和蛋白质印迹分析检测肠道通透性、促破骨细胞因子表达、成骨和破骨细胞活性。此外，通过 16S rRNA 测序评估 GM 的组成和丰度，并通过代谢组学测量粪便短链脂肪酸 (SCFA) 水平。

结果

我们的研究结果表明，FMT 抑制了过度的破骨细胞生成并防止了 OVX 诱导的骨质流失。具体而言，与 OVX 组相比，FMT 增强了紧密连接蛋白（zonula occludens protein 1 (ZO-1) 和 Occludin）的表达，并抑制了促破骨细胞因子（肿瘤坏死因子-α (TNF-α) 和白细胞介素-1β（IL-1β））。此外，FMT 还优化了 GM 的组成和丰度，提高了粪便 SCFAs 水平（主要是乙酸和丙酸）。

结论

总的来说，基于 GM 骨轴，FMT 通过纠正 GM 的失衡、提高 SCFAs 水平、优化肠道通透性和抑制促破骨细胞因子的释放来预防 OVX 引起的骨丢失，这可能是一种替代选择作为未来预防和治疗PMOP的有希望的候选者。

本文的翻译潜力

该研究表明 GM 骨轴巧妙地参与 PMOP 以及 FMT 在重塑 GM 状态和改善 OVX 诱导的小鼠骨丢失中的作用。FMT可能成为未来预防和治疗PMOP的有希望的候选者。