Liu Chunjie, Zhou Shasha, Li Yan, Yin Xiaoqin, Li Pin
Department of Endocrinology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Endocrinol (Lausanne). 2024 Dec 2;15:1481364. doi: 10.3389/fendo.2024.1481364. eCollection 2024.
Central precocious puberty (CPP) is characterized by the premature activation of the hypothalamic-pituitary-gonadal axis, resulting in early onset of sexual development. The incidence of CPP has been rising in recent years, with approximately 90% of cases lacking a clearly identifiable etiology. While an association between precocious puberty and gut microbiota has been observed, the precise causal pathways and underlying mechanisms remain poorly understood. The study aims to investigate the potential mechanisms through which gut microbiota imbalances may contribute to CPP.
In this study, clinical information and fecal samples were collected from 50 CPP patients and 50 healthy control subjects. The fecal samples were analyzed by 16S rDNA sequencing and UPLC-MS/MS metabolic analysis. Spearman correlation analysis was used to identify the relationships between gut microbiota and metabolites.
The gut microbiota composition in CPP patients was significantly different from that in healthy controls, characterized by an increased abundance of and a decreased abundance of . Additionally, significant differences were observed in metabolite composition between the CPP and control groups. A total of 51 differentially expressed metabolites were identified, with 32 showing significant upregulation and 19 showing significant downregulation in the CPP group. Furthermore, Spearman correlation analysis indicated that gut microbiota dysbiosis may contribute to altered metabolic patterns in CPP, given its involvement in the regulation of several metabolic pathways, including phenylalanine and tyrosine biosynthesis and metabolism, the citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolism, and tryptophan metabolism.
The study revealed the gut microbial and metabolite characteristics of CPP patients by integrating microbiome and metabolomics analyses. Moreover, several key metabolic pathways involved in the onset and progression of CPP were identified, which were regulated by gut microbiota. These findings broaden the current understanding of the complex interactions between gut microbial metabolites and CPP, and provide new insights into the pathogenesis and clinical management of CPP.
中枢性性早熟（CPP）的特征是下丘脑 - 垂体 - 性腺轴过早激活，导致性发育提前开始。近年来CPP的发病率一直在上升，约90%的病例病因不明。虽然已观察到性早熟与肠道微生物群之间存在关联，但确切的因果途径和潜在机制仍知之甚少。本研究旨在探讨肠道微生物群失衡可能导致CPP的潜在机制。
在本研究中，收集了50例CPP患者和50例健康对照者的临床信息和粪便样本。粪便样本通过16S rDNA测序和UPLC - MS/MS代谢分析进行检测。采用Spearman相关性分析来确定肠道微生物群与代谢物之间的关系。
CPP患者的肠道微生物群组成与健康对照组有显著差异，其特征是 丰度增加而 丰度降低。此外，CPP组和对照组之间的代谢物组成也存在显著差异。共鉴定出51种差异表达的代谢物，其中32种在CPP组中显著上调，19种在CPP组中显著下调。此外，Spearman相关性分析表明，肠道微生物群失调可能导致CPP患者代谢模式改变，因为它参与了多种代谢途径的调节，包括苯丙氨酸和酪氨酸的生物合成与代谢、柠檬酸循环（TCA循环）、乙醛酸和二羧酸代谢以及色氨酸代谢。
本研究通过整合微生物组学和代谢组学分析揭示了CPP患者的肠道微生物和代谢物特征。此外，还确定了CPP发病和进展过程中涉及的几个关键代谢途径，这些途径受肠道微生物群调节。这些发现拓宽了目前对肠道微生物代谢物与CPP之间复杂相互作用的理解，并为CPP的发病机制和临床管理提供了新的见解。
