Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics
Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics
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DOI：
10.1172/jci86062
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发表时间：
2016-06-01
影响因子：
15.9
通讯作者：
Pacifici, Roberto
中科院分区：
文献类型：
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作者：
Li, Jau-Yi;Chassaing, Benoit;Pacifici, Roberto
一个益生菌群影响后生动物宿主的许多生理过程，包括发育和肠道内稳态。在这里，我们已经表明，肠道微生物群调节性类固醇缺乏引起的炎症反应，导致骨小梁丢失。在小鼠模型中，性类固醇缺乏增加了肠道通透性，扩增了Th 17细胞，并上调了小肠和BM中的破骨细胞生成细胞因子TNF α（TNF）、RANKL和IL-17。在无菌（GF）小鼠中，性类固醇缺乏未能增加破骨细胞生成细胞因子的产生，刺激骨吸收，并导致骨小梁丢失，这表明肠道微生物群在性类固醇缺乏诱导的骨小梁丢失中处于中心地位。此外，我们证明了每周两次用益生菌鼠李糖乳杆菌GG（LGG）或市售益生菌补充剂VSL#3治疗性类固醇缺乏小鼠可降低肠道通透性，抑制肠道和BM炎症，并完全防止骨质流失。相反，补充非益生菌E.大肠杆菌或突变型LGG不能产生保护性。总之，这些数据突出了肠道微生物群和增加的肠道通透性在触发炎症途径中的作用，这些炎症途径对于诱导性类固醇缺乏小鼠的骨质流失至关重要。我们的数据进一步表明，降低肠道通透性的益生菌有可能作为绝经后骨质疏松症的治疗策略。
A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNF alpha (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency-induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid-deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss. In contrast, supplementation with a nonprobiotic strain of E. coli or a mutant LGG was not protective. Together, these data highlight the role that the gut luminal microbiota and increased gut permeability play in triggering inflammatory pathways that are critical for inducing bone loss in sex steroid-deficient mice. Our data further suggest that probiotics that decrease gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis.