Introduction

Aging-related osteoporosis is considered as a serious public health concern for middle-aged and elderly people, with an intricated pathogenesis including the recently identified aging-induced immunological dysfunction and gut microbial disorder. The intervention based on dietary prebiotics is recommended to retain bone health and postpone the progression of osteoporosis.

Objectives

As a well-defined prebiotic, 2′-fucosyllactose (2′-FL) has been thoroughly validated with positive effect on systemic health and was proposed in this study to unveil its intervention on aging-related osteoporosis, as well as the underlying mechanisms involving the gut microecology and innate immunity.

Methods

The effects of dietary 2′-FL on osteoporosis phenotypes were identified by evaluating the severity of bone loss and microstructure damage in natural aging mice. The mechanisms relying on innate immune profile, intestinal barrier function, and gut microbial homeostasis, were analyzed to elucidate the signaling axis. The detailed molecular signaling was validated based on LPS-stimulated RAW 264.7 murine macrophages.

Results

The results indicated that 12-week 2′-FL intervention retrieved bone loss and microstructure damage in natural aging mice. Also, 2′-FL alleviated aging-induced colonic inflammation, gut barrier dysfunction, and abnormal expression of intestinal tight-junction protein. The impact of 2′-FL treatment on the aging-induced gut microbial dysbiosis was validated by restoring gut microbiota diversity, recovering the abundance of Bifidobacterium, Prevotellaceae and Akkermansia, and inhibiting the growth of Stenotrophomonas. Flow cytometry analysis revealed changes in dendritic cell (DC) and macrophage subsets with age, and a decrease in M1-polarized macrophages was observed in 2′-FL-treated aged mice and RAW264.7 cells potentially through the interaction with toll-like receptor 4 (TLR4) to suppress NF-κB signaling and the secretion of proinflammatory factors.

Conclusion

These findings highlight the preventive effect of 2′-FL on aging-associated osteoporosis by regulating gut microbial homeostasis and innate immune responses.

中文翻译：

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2'-岩藻糖基乳糖通过恢复肠道微生物和先天免疫稳态来改善与衰老相关的骨质疏松症

 介绍

衰老相关骨质疏松症被认为是中老年人严重的公共卫生问题，其发病机制错综复杂，包括最近发现的衰老诱导的免疫功能障碍和肠道微生物疾病。建议基于膳食益生元的干预以保持骨骼健康并延缓骨质疏松症的进展。

 目标

作为一种定义明确的益生元，2'-岩藻糖基乳糖 （2'-FL） 已得到全面验证，对全身健康有积极影响，并在本研究中提出，以揭示其对衰老相关骨质疏松症的干预，以及涉及肠道微生态和先天免疫的潜在机制。

 方法

通过评估自然衰老小鼠骨质流失和微观结构损伤的严重程度，确定饮食 2′-FL 对骨质疏松症表型的影响。分析依赖于先天免疫谱、肠道屏障功能和肠道微生物稳态的机制，以阐明信号轴。基于 LPS 刺激的 RAW 264.7 小鼠巨噬细胞验证了详细的分子信号传导。

 结果

结果表明，为期 12 周的 2'-FL 干预可挽救自然衰老小鼠的骨质流失和微观结构损伤。此外，2′-FL 减轻了衰老诱导的结肠炎症、肠道屏障功能障碍和肠道紧密连接蛋白的异常表达。通过恢复肠道微生物群多样性、恢复双歧杆菌、Prevotellaceae 和 Akkermansia 的丰度以及抑制 Stenotrophomonas 的生长，验证了 2′-FL 处理对衰老诱导的肠道微生物失调的影响。流式细胞术分析显示树突状细胞 （DC） 和巨噬细胞亚群随年龄变化，在 2′-FL 处理的老年小鼠和 RAW264.7 细胞中观察到 M1 极化巨噬细胞的减少，这可能是通过与 toll 样受体 4 （TLR4） 相互作用抑制 NF-κB 信号传导和促炎因子的分泌。

 结论

这些发现强调了 2′-FL 通过调节肠道微生物稳态和先天免疫反应对衰老相关骨质疏松症的预防作用。