益生菌对脂肪组织中转化生长因子-β1的抑制作用可减轻实验性诱导的多囊卵巢综合征中的代谢紊乱。

Suppression of adipose TGF-β1 by probiotics alleviates metabolic disturbance in experimentally induced PCOS.

作者信息

Olaniyi Kehinde S, Okara Doris O, Areloegbe Stephanie E

机构信息

Cardio/Endo-metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado Ekiti 360101, Nigeria.

出版信息

Prostaglandins Other Lipid Mediat. 2025 Jun;178:106989. doi: 10.1016/j.prostaglandins.2025.106989. Epub 2025 Mar 26.

DOI:10.1016/j.prostaglandins.2025.106989

PMID:40154941

Abstract

BACKGROUND

Polycystic ovarian syndrome (PCOS) is critically characterized with metabolic and endocrine dysfunctions, precipitating metabolic syndrome and infertility in reproductive aged women. Adipose tissue dysfunction has been implicated in the pathogenesis of metabolic syndrome, including in PCOS individuals. Probiotics are healthy bacteria in the gut that regulate metabolic health. However, the impact of probiotics on adipose-driven metabolic syndrome has not been reported. The present study therefore hypothesized that probiotics would attenuates metabolic disturbance in experimental PCOS rat model, probably by suppression of TGF-β1.

MATERIALS AND METHODS

Eight-week-old female Wistar rats were randomly allotted into four groups (n = 5). Administration of letrozole (1 mg/kg p.o) for 21 days induced PCOS, thereafter the animals were treated with 3x10 CFU (p. o) of probiotics for six weeks.

RESULTS

Letrozole-induced PCOS rats were characterized with elevated circulating testosterone, and multiple ovarian cysts. In addition, rats with PCOS developed increased body weight, which was also accompanied with insulin resistance, hyperinsulinemia, and increased leptin, and decreased adiponectin and adipose TG, as well as elevated adipose lipase. Inflammatory markers (NF-kB, TNF-α) were elevated, while antioxidant defense (GSH) was depleted in PCOS animals. A significant increase in adipose TGF-β1, caspase-6 and HDAC2 levels was observed in PCOS rats when compared with the control. Immunohistochemical evaluation of adipose tissue also showed severe expression of NLRP3 in PCOS rats and these changes were accompanied by increased level of TGF-β1. However, treatment with probiotics reversed these aberrant systemic and adipose tissue changes in PCOS model.

CONCLUSION

The present results suggest the therapeutic benefit of probiotics against metabolic disturbance in PCOS model through suppression of TGF-β1-dependent pathway.

摘要

背景

多囊卵巢综合征（PCOS）的关键特征是代谢和内分泌功能障碍，可导致育龄妇女出现代谢综合征和不孕。脂肪组织功能障碍与代谢综合征的发病机制有关，包括PCOS患者。益生菌是肠道中的有益细菌，可调节代谢健康。然而，益生菌对脂肪驱动的代谢综合征的影响尚未见报道。因此，本研究假设益生菌可能通过抑制TGF-β1减轻实验性PCOS大鼠模型中的代谢紊乱。

材料与方法

将8周龄雌性Wistar大鼠随机分为四组（n = 5）。给予来曲唑（1 mg/kg口服）21天诱导PCOS，此后动物用3×10⁹ CFU（口服）的益生菌治疗六周。

结果

来曲唑诱导的PCOS大鼠具有循环睾酮升高和多个卵巢囊肿的特征。此外，PCOS大鼠体重增加，同时伴有胰岛素抵抗、高胰岛素血症、瘦素增加、脂联素和脂肪甘油三酯降低以及脂肪酶升高。炎症标志物（NF-κB、TNF-α）升高，而PCOS动物的抗氧化防御（谷胱甘肽）减少。与对照组相比，PCOS大鼠脂肪组织中TGF-β1、半胱天冬酶-6和HDAC2水平显著升高。脂肪组织的免疫组织化学评估也显示PCOS大鼠中NLRP3的严重表达，这些变化伴随着TGF-β1水平的升高。然而，益生菌治疗逆转了PCOS模型中这些异常的全身和脂肪组织变化。