Abstract：
OBJECTIVE: Precocious puberty (PP) may lead to many adverse outcomes. Recent evidence suggests that PP is a gut-brain disease. On the other hand, the use of glycyrrhizin, a natural sweetener, has become popular in the past decade. Glycyrrhizin possesses various health benefits, but its impact on PP has yet to be investigated. We aimed to explore the protective effects of glycyrrhizin against PP in both humans (observational) and animals (interventional).
METHODS: In the human cohort, we investigated the association between glycyrrhizin consumption and risk of PP. In the animal experiment, we observed puberty onset after feeding danazol-induced PP rats with glycyrrizin. Blood, fecal, and hypothalamic samples were harvested to evaluate potential mechanistic pathways. We also performed a fecal microbiota transplantation to confirm to causal relationship between glycyrrhizin and PP risk.
RESULTS: Glycyrrhizin exhibited a protective effect against PP in children (OR 0.60, 95%CI: 0.39-0.89, p = 0.013), primarily driven by its significance in girls, while no significant effect was observed in boys. This effect was consistent with findings in rodents. These benefits were achieved through the modulation of the gut microbiome, which functionally suppressed the hypothalamic-pituitary-gonadal axis and prevented PP progression. A fecal microbiota transplantation indicated that the causal correlation between glycyrrhizin intake and PP is mediated by the gut microbiome alterations.
CONCLUSIONS: Our findings suggest that glycyrrhizin can protect against PP by altering the gut microbiome. Long term use of glycyrrhizin is safe and tolerable. Therefore, glycyrrhizin can serve as a safe and affordable complementary therapy for PP.
METHODS: In the human cohort, we investigated the association between glycyrrhizin consumption and risk of PP. In the animal experiment, we observed puberty onset after feeding danazol-induced PP rats with glycyrrizin. Blood, fecal, and hypothalamic samples were harvested to evaluate potential mechanistic pathways. We also performed a fecal microbiota transplantation to confirm to causal relationship between glycyrrhizin and PP risk.
RESULTS: Glycyrrhizin exhibited a protective effect against PP in children (OR 0.60, 95%CI: 0.39-0.89, p = 0.013), primarily driven by its significance in girls, while no significant effect was observed in boys. This effect was consistent with findings in rodents. These benefits were achieved through the modulation of the gut microbiome, which functionally suppressed the hypothalamic-pituitary-gonadal axis and prevented PP progression. A fecal microbiota transplantation indicated that the causal correlation between glycyrrhizin intake and PP is mediated by the gut microbiome alterations.
CONCLUSIONS: Our findings suggest that glycyrrhizin can protect against PP by altering the gut microbiome. Long term use of glycyrrhizin is safe and tolerable. Therefore, glycyrrhizin can serve as a safe and affordable complementary therapy for PP.
摘要：
目的：性早熟（PP）可能导致许多不良结局。最近的证据表明PP是一种肠脑疾病。另一方面,使用甘草酸，一种天然甜味剂,在过去的十年里变得很流行。甘草酸具有多种健康益处，但其对PP的影响尚待调查。我们旨在探索甘草酸对人类（观察）和动物（干预）的PP的保护作用。
方法：在人类队列中，我们调查了甘草酸消费与PP风险之间的关系。在动物实验中,我们观察到用甘蓝嗪喂养达那唑诱导的PP大鼠后青春期开始。血，粪便,收集下丘脑样本以评估潜在的机制途径。我们还进行了粪便微生物移植，以确认甘草酸和PP风险之间的因果关系。
结果：甘草酸保护女孩，但不是男孩，从PP（OR0.60，95CI：0.39-0.89，p=0.013）。这种效应与啮齿动物的发现一致。这些好处是通过调节肠道微生物组实现的，在功能上抑制下丘脑-垂体-性腺轴并阻止PP进展。粪便微生物群移植表明，甘草甜素摄入量与PP之间的因果关系是由肠道微生物组改变介导的。
结论：我们的研究结果表明，甘草甜素可以通过改变肠道微生物组来预防PP。长期使用甘草酸是安全和耐受的。因此,甘草酸可以作为PP的安全和负担得起的补充疗法。
方法：在人类队列中，我们调查了甘草酸消费与PP风险之间的关系。在动物实验中,我们观察到用甘蓝嗪喂养达那唑诱导的PP大鼠后青春期开始。血，粪便,收集下丘脑样本以评估潜在的机制途径。我们还进行了粪便微生物移植，以确认甘草酸和PP风险之间的因果关系。
结果：甘草酸保护女孩，但不是男孩，从PP（OR0.60，95CI：0.39-0.89，p=0.013）。这种效应与啮齿动物的发现一致。这些好处是通过调节肠道微生物组实现的，在功能上抑制下丘脑-垂体-性腺轴并阻止PP进展。粪便微生物群移植表明，甘草甜素摄入量与PP之间的因果关系是由肠道微生物组改变介导的。
结论：我们的研究结果表明，甘草甜素可以通过改变肠道微生物组来预防PP。长期使用甘草酸是安全和耐受的。因此,甘草酸可以作为PP的安全和负担得起的补充疗法。
