Abstract：
METHODS: The disturbance of the hypothalamic-pituitary-gonadal (HPG) axis, gut microbiota (GM) community, and short-chain fatty acids (SCFAs) is a triggering factor for pubertal onset. The study investigates the effects of the long-term intake of aspartame on puberty and GM in animals and humans.
RESULTS: Aspartame-fed female offspring rats result in vaginal opening time prolongation, serum estrogen reduction, and serum luteinizing hormone elevation. , 60 mg kg-1 aspartame treatment decreases the mRNA levels of gonadotropin-releasing hormone (GnRH), Kiss1, and G protein-coupled receptor 54 (GPR54), increases the mRNA level of RFamide-related peptide-3 (RFRP-3), and decreases the expression of GnRH neurons in the hypothalamus. Significant differences in relative bacterial abundance at the genus levels and decreased fecal SCFA levels are noted by 60 mg kg-1 aspartame treatment. Among which, Escherichia-Shigella is negatively correlated with several SCFAs. In girls, high-dose aspartame consumption decreases the risk of precocious puberty.
CONCLUSIONS: Aspartame reduces the chance of puberty occurring earlier than usual in female offspring and girls. Particularly, 60 mg kg-1 aspartame-fed female offspring delays pubertal onset through the dysregulation of HPG axis and GM composition by inhibiting the Kiss1/GPR54 system and inducing the RFRP-3. An acceptable dose of aspartame should be recommended during childhood.
RESULTS: Aspartame-fed female offspring rats result in vaginal opening time prolongation, serum estrogen reduction, and serum luteinizing hormone elevation. , 60 mg kg-1 aspartame treatment decreases the mRNA levels of gonadotropin-releasing hormone (GnRH), Kiss1, and G protein-coupled receptor 54 (GPR54), increases the mRNA level of RFamide-related peptide-3 (RFRP-3), and decreases the expression of GnRH neurons in the hypothalamus. Significant differences in relative bacterial abundance at the genus levels and decreased fecal SCFA levels are noted by 60 mg kg-1 aspartame treatment. Among which, Escherichia-Shigella is negatively correlated with several SCFAs. In girls, high-dose aspartame consumption decreases the risk of precocious puberty.
CONCLUSIONS: Aspartame reduces the chance of puberty occurring earlier than usual in female offspring and girls. Particularly, 60 mg kg-1 aspartame-fed female offspring delays pubertal onset through the dysregulation of HPG axis and GM composition by inhibiting the Kiss1/GPR54 system and inducing the RFRP-3. An acceptable dose of aspartame should be recommended during childhood.
摘要：
方法：下丘脑-垂体-性腺（HPG）轴的紊乱，肠道微生物群（GM）群落，短链脂肪酸（SCFA）是青春期发病的触发因素。该研究调查了长期摄入阿斯巴甜对动物和人类青春期和转基因的影响。
结果：饲喂阿斯巴甜的雌性后代大鼠导致阴道开放时间延长，血清雌激素减少，和血清黄体生成素升高。,60mgkg-1阿斯巴甜治疗可降低促性腺激素释放激素（GnRH）的mRNA水平，Kiss1和G蛋白偶联受体54（GPR54），增加RFamide相关肽-3（RFRP-3）的mRNA水平，并降低下丘脑GnRH神经元的表达。通过60mgkg-1阿斯巴甜处理，发现属水平的相对细菌丰度存在显着差异，粪便SCFA水平降低。其中,大肠杆菌-志贺氏菌与几种SCFA呈负相关。在女孩中，大剂量服用阿斯巴甜可降低性早熟的风险.
结论：阿斯巴甜减少了雌性后代和女孩青春期发生的机会。特别是,60mgkg-1阿斯巴甜喂养的雌性后代通过抑制Kiss1/GPR54系统并诱导RFRP-3，通过HPG轴和GM组成的失调来延迟青春期的发作。在儿童期应推荐可接受剂量的阿斯巴甜。
结果：饲喂阿斯巴甜的雌性后代大鼠导致阴道开放时间延长，血清雌激素减少，和血清黄体生成素升高。,60mgkg-1阿斯巴甜治疗可降低促性腺激素释放激素（GnRH）的mRNA水平，Kiss1和G蛋白偶联受体54（GPR54），增加RFamide相关肽-3（RFRP-3）的mRNA水平，并降低下丘脑GnRH神经元的表达。通过60mgkg-1阿斯巴甜处理，发现属水平的相对细菌丰度存在显着差异，粪便SCFA水平降低。其中,大肠杆菌-志贺氏菌与几种SCFA呈负相关。在女孩中，大剂量服用阿斯巴甜可降低性早熟的风险.
结论：阿斯巴甜减少了雌性后代和女孩青春期发生的机会。特别是,60mgkg-1阿斯巴甜喂养的雌性后代通过抑制Kiss1/GPR54系统并诱导RFRP-3，通过HPG轴和GM组成的失调来延迟青春期的发作。在儿童期应推荐可接受剂量的阿斯巴甜。
