Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure.

Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure.
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DOI:
10.1080/19490976.2023.2190304
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发表时间:
2023-01
期刊:
影响因子:
12.2
通讯作者:
--
中科院分区:
医学2区
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随着对肠-骨轴的了解越来越多,越来越多的基于肠道微生物调节绝经后骨质疏松症的治疗研究正在进行。本研究在前期工作的基础上,进一步探讨了鼠李糖乳杆菌(Lactobacillus rhamnosus GG,LGG)对去势大鼠的治疗作用及其免疫学和微生态学机制。我们发现LGG治疗通过改变骨微结构、骨生物力学和CTX-I、PINP、Ca和RANKL表达水平在OVX大鼠中具有保护作用。LGG在促进成骨方面更有优势,这可能是减轻骨质疏松的原因。在纵隔淋巴结和骨髓中,Th 17细胞与Treg细胞失衡,RORγt和FOXP 3表达遵循类似的趋势。结肠和骨髓中TNF-α和IL-17表达增加,TGF-β和IL-10表达降低;但LGG治疗可调节这些变化,并显著改善Th 17/Treg平衡。关于肠屏障,我们发现LGG治疗改善了雌激素缺乏引起的炎症和粘膜损伤,并增加了GLP-2 R和紧密连接蛋白的表达。重要的是,16 S rRNA测序显示雌激素缺乏期间厚壁菌门/拟杆菌门比率显著增加。优势肠道植物群在组成上表现出显著差异; LGG处理调节了OVX中不平衡的各种属,沿着修改了其他组在肠道屏障、炎症发展和胆汁酸代谢方面没有显著变化的那些属。总体而言,LGG通过调节肠道微生物组和肠道屏障以及刺激肠道和骨骼中的Th 17/Treg平衡来改善雌激素缺乏诱导的骨质疏松症。图形摘要。LGG通过调节肠道微生物组和肠道屏障以及改善肠道中Th 17/Treg平衡来减轻卵巢切除大鼠的骨质疏松症。
With increasing knowledge about the gut – bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being conducted. Based on our previous work, this study was conducted to further investigate the therapeutic effects of Lactobacillus rhamnosus GG (LGG) on ovariectomized (OVX) model rats and the immunological and microecological mechanisms involved. We found a protective effect of LGG treatment in OVX rats through changes in bone microarchitecture, bone biomechanics, and CTX-I, PINP, Ca, and RANKL expression levels. LGG was more advantageous in promoting osteogenesis, which may be responsible for the alleviation of osteoporosis. Th17 cells were imbalanced with Treg cells in mediastinal lymph nodes and bone marrow, with RORγt and FOXP3 expression following a similar trend. TNF-α and IL-17 expression in colon and bone marrow increased, while TGF-β and IL-10 expression decreased; however, LGG treatment modulated these changes and improved the Th17/Treg balance significantly. Regarding the intestinal barrier, we found that LGG treatment ameliorated estrogen deficiency-induced inflammation and mucosal damage and increased the expression of GLP-2 R and tight junction proteins. Importantly, 16S rRNA sequencing showed a significant increase in the Firmicutes/Bacteroidetes ratio during estrogen deficiency. Dominant intestinal flora showed significant differences in composition; LGG treatment regulated the various genera that were imbalanced in OVX, along with modifying those that did not change significantly in other groups with respect to the intestinal barrier, inflammation development, and bile acid metabolism. Overall, LGG ameliorated estrogen deficiency-induced osteoporosis by regulating the gut microbiome and intestinal barrier and stimulating Th17/Treg balance in gut and bone. Graphical summary. LGG alleviates osteoporosis in ovariectomized rats by modulating the gut microbiome and intestinal barrier and improving Th17/Treg balance in gut- bone.
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