Lobetyolin重塑肠道微生物群和胆汁酸代谢，以改善小鼠雄激素驱动的PCOS表型
Lobetyolin reshapes gut microbiota and bile acid metabolism to improve androgen-driven PCOS phenotypes in mice.
摘要(中文译文)
为阐明党参炔苷（lobetyolin，LT）通过调节肠道菌群-胆汁酸轴，多靶点调控高雄激素血症、胰岛素抵抗、慢性低度炎症及子宫内膜功能障碍，从而打破恶性循环、改善多囊卵巢综合征（polycystic ovary syndrome，PCOS）病理表型的分子机制，进而为LT作为PCOS系统性治疗药物的开发奠定理论基础并提供实验验证。采用脱氢表雄酮（DHEA）诱导的PCOS小鼠模型，给予LT腹腔注射28天。监测血清激素水平、葡萄糖耐量及动情周期。通过qPCR评估卵巢类固醇合成酶表达（CYP11A1、CYP17A1和CYP19A1），通过ELISA定量炎症标志物（IL-6、TNF-α、TLR4和NF-κB）。进行16S rRNA测序分析肠道菌群，并开展靶向胆汁酸代谢组学分析。通过血管内皮生长因子A（VEGFA）/血管内皮生长因子受体（VEGFR2）、金属蛋白酶组织抑制因子1/2（TIMP1/2）及基质金属蛋白酶2/9（MMP2/9）评估子宫分子标志物。LT恢复了动情周期，降低了LH/FSH比值和血清睾酮水平，并改善了胰岛素敏感性。雄激素网络调控方面：LT降低CYP11A1/CYP17A1并升高CYP19A1，呈现“上游抑制-下游激活”模式。LT还提高了α多样性，调整了F/B比值，富集了/，并抑制了。较高的HCA和TCDCA水平与代谢改善相关。LT通过下调VEGFA/VEGFR2和MMP2/9，以及过表达TIMP1/2，减轻了子宫病理性血管重塑。LT通过调节菌群-胆汁酸轴，协同改善高雄激素血症、胰岛素抵抗、慢性炎症及子宫功能障碍。该干预阻断了PCOS的病理级联反应。上述发现为PCOS预防的后续机制研究提供了依据。
Abstract
To clarify the molecular mechanisms through which lobetyolin (LT) modifies the gut microbiota-bile acid axis to multitarget the regulation of hyperandrogenism, insulin resistance, chronic low-grade inflammation, and endometrial dysfunction, consequently breaking the vicious cycle and improving the pathological phenotype of polycystic ovary syndrome (PCOS), thereby establishing a theoretical basis and experimental validation for the advancement of LT as a systemic therapeutic agent for PCOS. A DHEA-induced PCOS murine model was administered LT (i.p. for 28 days). We monitored hormone levels in the serum, glucose tolerance, and estrus cycle. Ovarian steroidogenic enzyme expression (CYP11A1, CYP17A1, and CYP19A1) was assessed by qPCR, while inflammatory markers (IL-6, TNF-α, TLR4, and NF-κB) were quantified by ELISA.16S rRNA sequencing was performed for gut microbiota and focused bile acid metabolomics. Uterine molecular markers were evaluated through vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor (VEGFR2), tissue inhibitor of metalloproteinases 1(TIMP1/2), and matrix metalloproteinase 2/9 (MMP2/9). LT restored estrous cyclicity, lowered the LH/FSH ratio and serum testosterone levels, and improved insulin sensitivity. Androgen Network Modulation: LT decreased CYP11A1/CYP17A1 and elevated CYP19A1, showing "upstream inhibition-downstream activation." LT also boosted α-diversity, adjusted the F/B ratio, enriched /, and inhibited . Higher HCA and TCDCA levels are associated with improved metabolism. LT alleviated pathological vascular remodeling in the uterus by downregulating VEGFA/VEGFR2 and MMP2/9, and by overexpressing TIMP1/2. LT modulates the microbiota-bile acid axis to coordinately ameliorate hyperandrogenism, insulin resistance, chronic inflammation, and uterine dysfunction. This intervention blocks the pathological cascade of PCOS. The findings provide a subsequent mechanistic studies on PCOS prevention.
如何引用
AMA
Lijuan Li, Pingping Lin, Siyuan Liu, Yuning Zhang, Siqi Wang, Jingtao Liang, et al. Lobetyolin reshapes gut microbiota and bile acid metabolism to improve androgen-driven PCOS phenotypes in mice.. Frontiers in microbiology. 2026; doi:10.3389/fmicb.2026.1810261.
APA
Lijuan Li, Pingping Lin, Siyuan Liu, Yuning Zhang, Siqi Wang, Jingtao Liang, et al (2026). Lobetyolin reshapes gut microbiota and bile acid metabolism to improve androgen-driven PCOS phenotypes in mice.. Frontiers in microbiology. https://doi.org/10.3389/fmicb.2026.1810261
GB/T 7714
Lijuan Li, Pingping Lin, Siyuan Liu, Yuning Zhang, Siqi Wang, Jingtao Liang, et al. Lobetyolin reshapes gut microbiota and bile acid metabolism to improve androgen-driven PCOS phenotypes in mice.[J]. Frontiers in microbiology, 2026 doi:10.3389/fmicb.2026.1810261.
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