Table 2_Butyric acid ameliorates PCOS-related reproductive dysfunction through gut-brain-ovary axis signaling and ovarian steroidogenic factor activation.doc

BackgroundButyric acid deficiency is implicated in polycystic ovary syndrome (PCOS), as evidenced by reduced levels in both clinical and preclinical models. Sodium butyrate (NaBu),a butyric acid substitute, has demonstrated therapeutic potential through gut-brain axis modulation, anti-inflammatory effects, and reproductive function protection. This study investigates NaBu’s mechanistic role in PCOS pathophysiology.
MethodsPCOS rats received lipo-coated NaBu diet for three weeks. Systemic and tissue analyses included: serum hormone profiling, lipid metabolism assessment, ovarian/colonic histopathology, Short-chain fatty acids (SCFAs) analysis, and proteomics analysis. Primary granulosa cell cultures with lentiviral transfection elucidated molecular mechanisms. Reproductive performance was evaluated longitudinally.
ResultsTreatment with NaBu in PCOS rats resulted in reduced food intake, inhibited weight gain, improved abnormal lipid metabolism, restored estrus cycles and ovulation, lower serum levels of testosterone (T), insulin (INS), and luteinizing hormone (LH), and higher levels of estradiol (E2) and progesterone (P4). Additionally, NaBu treatment improved the morphology of polycystic ovaries, elevated colonic levels of G protein-coupled receptor 41 (GPR41), peptide tyrosine-tyrosine (PYY), and butyric acid, and enhanced reproductive performance in PCOS rats. Proteomic analysis and cell experiments suggested that upregulation of Cytochrome P450 1b1 (Cyp1b1) may play a crucial role in regulating E2 metabolism and P4 production, potentially contributing to the pathogenesis of PCOS and ovarian dysfunction.
ConclusionThese findings indicate that NaBu may exert its regulatory effects on appetite and hormone levels in the hypothalamus through the gut-brain-ovary axis, modulating the expression of ovarian steroidogenic factors, thereby improving follicular development and granulosa cell function, and enhancing reproductive performance.

研究背景
丁酸缺乏与多囊卵巢综合征（polycystic ovary syndrome, PCOS）密切相关，临床及临床前模型中丁酸水平降低均可为该关联提供佐证。丁酸钠（sodium butyrate, NaBu）作为丁酸的替代制剂，可通过调控肠-脑轴、发挥抗炎作用以及保护生殖功能展现出治疗潜力。本研究旨在阐明丁酸钠在多囊卵巢综合征病理生理过程中的调控机制。

研究方法
多囊卵巢综合征模型大鼠接受脂质包被丁酸钠日粮干预，干预周期为三周。本研究开展的整体与组织层面检测分析包括：血清激素谱检测、脂质代谢水平评估、卵巢及结肠组织病理学检查、短链脂肪酸（short-chain fatty acids, SCFAs）定量分析以及蛋白质组学分析。通过慢病毒转染的原代颗粒细胞培养实验，进一步解析其潜在分子调控机制，并对大鼠的生殖性能进行了纵向追踪评估。

研究结果
丁酸钠干预可降低多囊卵巢综合征模型大鼠的摄食量，抑制体质量异常增长，改善异常脂质代谢状态，恢复发情周期与排卵功能；同时可降低血清睾酮（testosterone, T）、胰岛素（insulin, INS）及黄体生成素（luteinizing hormone, LH）水平，升高雌二醇（estradiol, E2）与孕酮（progesterone, P4）水平。此外，丁酸钠干预可改善多囊卵巢的组织形态，升高结肠组织中G蛋白偶联受体41（G protein-coupled receptor 41, GPR41）、酪酪肽（peptide tyrosine-tyrosine, PYY）的表达水平以及丁酸的含量，并提升多囊卵巢综合征模型大鼠的生殖性能。蛋白质组学分析与细胞实验结果显示，细胞色素P450 1b1（cytochrome P450 1b1, Cyp1b1）的上调或许在调控雌二醇代谢与孕酮合成过程中发挥关键作用，或参与多囊卵巢综合征的发病机制及卵巢功能异常的发生。

研究结论
本研究结果表明，丁酸钠或可通过肠-脑-卵巢轴对下丘脑的摄食行为与激素水平发挥调控作用，同时调节卵巢类固醇生成因子的表达，进而改善卵泡发育与颗粒细胞功能，最终提升生殖性能。