Key Laboratory of Animal Biotechnology, Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, China.
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.
Microbiol Spectr. 2023 Jun 15;11(3):e0014923. doi: 10.1128/spectrum.00149-23. Epub 2023 May 4.
Decreased estrogen level is one of the main causes of lipid metabolism disorders and coronary heart disease in women after menopause. Exogenous estradiol benzoate is effective to some extent in alleviating lipid metabolism disorders caused by estrogen deficiency. However, the role of gut microbes in the regulation process is not yet appreciated. The objective of this study was to investigate the effects of estradiol benzoate supplementation on lipid metabolism, gut microbiota, and metabolites in ovariectomized (OVX) mice and to reveal the importance of gut microbes and metabolites in the regulation of lipid metabolism disorders. This study found that high doses of estradiol benzoate supplementation effectively attenuated fat accumulation in OVX mice. There was a significant increase in the expression of genes enriched in hepatic cholesterol metabolism and a concomitant decrease in the expression of genes enriched in unsaturated fatty acid metabolism pathways. Further screening of the gut for characteristic metabolites associated with improved lipid metabolism revealed that estradiol benzoate supplementation influenced major subsets of acylcarnitine metabolites. Ovariectomy significantly increased the abundance of characteristic microbes that are significantly negatively associated with acylcarnitine synthesis, such as and Eubacterium ruminantium group bacteria, while estradiol benzoate supplementation significantly increased the abundance of characteristic microbes that are significantly positively associated with acylcarnitine synthesis, such as and spp. The use of pseudosterile mice with gut microbial deficiency greatly facilitated the synthesis of acylcarnitine due to estradiol benzoate supplementation and also alleviated lipid metabolism disorders to a greater extent in OVX mice. Our findings establish a role for gut microbes in the progression of estrogen deficiency-induced lipid metabolism disorders and reveal key target bacteria that may have the potential to regulate acylcarnitine synthesis. These findings suggest a possible route for the use of microbes or acylcarnitine to regulate disorders of lipid metabolism induced by estrogen deficiency.
雌激素水平降低是绝经后女性脂质代谢紊乱和冠心病的主要原因之一。苯甲酸雌二醇在一定程度上对外源性雌激素缺乏引起的脂质代谢紊乱有效。然而，肠道微生物在调节过程中的作用尚未得到重视。本研究旨在探讨苯甲酸雌二醇补充对去卵巢（OVX）小鼠脂质代谢、肠道微生物群和代谢物的影响，并揭示肠道微生物和代谢物在调节脂质代谢紊乱中的重要性。本研究发现，高剂量苯甲酸雌二醇补充有效地减轻了 OVX 小鼠的脂肪堆积。肝脏胆固醇代谢富集的基因表达显著增加，同时不饱和脂肪酸代谢途径富集的基因表达减少。进一步筛选与改善脂质代谢相关的肠道特征代谢物表明，苯甲酸雌二醇补充影响酰基辅酶 A 代谢物的主要亚群。卵巢切除显著增加了与酰基辅酶 A 合成显著负相关的特征微生物的丰度，如和真杆菌属细菌，而苯甲酸雌二醇补充显著增加了与酰基辅酶 A 合成显著正相关的特征微生物的丰度，如和 spp。使用缺乏肠道微生物的假无菌小鼠，由于苯甲酸雌二醇的补充，极大地促进了酰基辅酶 A 的合成，并在更大程度上缓解了 OVX 小鼠的脂质代谢紊乱。我们的研究结果确立了肠道微生物在雌激素缺乏诱导的脂质代谢紊乱进展中的作用，并揭示了可能具有调节酰基辅酶 A 合成潜力的关键靶细菌。这些发现为利用微生物或酰基辅酶 A 来调节雌激素缺乏引起的脂质代谢紊乱提供了一种可能的途径。
