Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.
Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.
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DOI：
10.1186/s13048-023-01227-w
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发表时间：
2023-07-14
影响因子：
4
通讯作者：
Yao, Bing
中科院分区：
文献类型：
--
作者：
Zhang, Hong;Zheng, Lu;Li, Chuwei;Jing, Jun;Li, Zhou;Sun, Shanshan;Xue, Tongmin;Zhang, Kemei;Xue, Mengqi;Cao, Chun;Ouyang, Lei;Qian, Zhang;Xu, Rui;He, Zhaowanyue;Ma, Rujun;Chen, Li;Yao, Bing
多囊卵巢综合征（PCOS）是一种常见的生殖内分泌紊乱，经常表现为低度炎症、促氧化活性和肠道生态失调。多囊卵巢综合征已成为全球女性不育的主要原因之一。最近，omega-3多不饱和脂肪酸（PUFAs）已被证明有益于多囊卵巢综合征患者的代谢紊乱。然而，其在多囊卵巢综合征病理生理中调节代谢和内分泌平衡的作用尚不清楚。在本研究中，我们旨在探讨omega-3 PUFAs如何通过调节肠道微生物群来缓解脱氢表雄酮（DHEA）诱导的PCOS小鼠卵巢功能障碍和胰岛素抵抗。我们先给雌性小鼠注射脱氢表雄酮，然后用omega-3 PUFAs治疗。采用16S核糖体DNA （rDNA）扩增子测序、粪便微生物群移植（FMT）和抗生素治疗来评估微生物群在omega-3 PUFAs对卵巢功能和胰岛素抵抗（IR）的调节中的作用。为了进一步研究肠道菌群对omega-3介导的卵巢和代谢保护作用的机制，我们研究了卵巢中的炎症和氧化应激标志物以及皮下和棕色脂肪组织中的产热标志物。我们发现口服补充omega-3 PUFAs可改善PCOS表型。16S rDNA分析显示，omega-3 PUFA治疗增加了肠道中有益细菌的丰度，从而减轻了dhea诱导的肠道生态失调。抗生素治疗和FMT实验进一步证明，omega-3益处的机制可能涉及直接作用于卵巢，抑制炎症细胞因子，如IL-1β、TNF-α和IL-18。此外，肠道微生物群通过减少皮下脂肪组织内的多室细胞和Ucp1、Pgc1a、Cited和Cox8b等产热标志物，在改善脂肪组织形态和功能方面发挥了关键作用。这些发现表明omega-3 PUFAs可以改善雄激素诱导的肠道菌群失调。肠道微生物群在多囊卵巢综合征小鼠中omega-3介导的IR保护作用的调节中起关键作用。此外，omega-3 pufa调节的与PCOS相关的卵巢功能障碍的改善可能涉及对卵巢抑制炎症的直接作用。我们的研究结果表明，补充omega-3可能是一种有希望的治疗多囊卵巢综合征的方法，通过调节肠道微生物群，减轻卵巢功能障碍和胰岛素抵抗。在线版本包含补充材料，下载地址：10.1186/s13048-023-01227-w。
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1β, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance. The online version contains supplementary material available at 10.1186/s13048-023-01227-w.
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