用L-岩藻糖调节肠道微生物群,减轻赭曲霉毒素A对原始卵泡形成的毒性。

Ruiting Wang, Jie Song, Muyu Cai, Yuan Xue, Jing Liu, Ning Zuo, Massimo De Felici, Junjie Wang, Wei Shen, Xiaofeng Sun
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摘要

赭曲霉毒素 A(OTA)是一种广泛存在的霉菌毒素,会对后代造成卵巢损伤。在这项研究中,我们调查了给暴露于 OTA 的怀孕小鼠服用左旋葡萄糖的潜在益处。研究结果表明,3.5 μg/d 的 OTA 会引起怀孕小鼠肠道组织和肠道微生物群的改变,导致局部和全身炎症的加剧。这种炎症影响到妊娠 3 dpp 后代的卵巢,发现 LPS 和 ROS 水平升高与卵母细胞数量显著减少和原始卵泡组装受损有关。此外,mRNA-Seq 分析表明卵巢转录组发生了显著变化,这些变化与各种 GO 术语和 KEGG 通路有关,特别是铁突变,这是一种公认的细胞死亡形式。有趣的是,在暴露于 OTA 后服用 0.3 g/kg b. w.暴露于 OTA 后,L-岩藻糖减轻了对母亲肠道组织和肠道微生物群以及后代卵巢的影响。将经过 L-岩藻糖处理的孕妇的肠道微生物群移植到暴露于 OTA 的母亲体内,也能获得类似的益处。这些研究结果表明,OTA 对母体肠道/肠道的炎症影响可传递给胎儿,导致后代卵巢缺陷,并支持使用 L-岩藻糖作为佐剂来抵消霉菌毒素对肠道微生物群的不利影响,特别是对生殖器官的影响。
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Gut microbiota modulation by L-Fucose as a strategy to alleviate Ochratoxin A toxicity on primordial follicle formation.

In this study, we investigated the potential benefits of L-Fucose administration to pregnant mice exposed to Ochratoxin A (OTA), a widespread mycotoxin, producing ovarian damage in offspring. The results showed that administration of 3.5 μg/d OTA induced alterations in intestinal tissues and gut microbiota of pregnant mice, leading to heightened local and systemic inflammation. This inflammatory affected the ovaries of their 3 dpp offspring, in which elevated levels of LPS and ROS were found associated to significant decreased oocyte count and impaired primordial follicle assembly. Moreover, mRNA-Seq analysis showed significant changes in ovarian transcriptomes linked to various GO terms and KEGG pathways, notably ferroptosis, a recognized form of cell death observed. Interestingly, administration of 0.3 g/kg b. w. L-Fucose following OTA exposure mitigated these effects on intestinal tissues and gut microbiota in mothers and on the offspring's ovaries. Similar benefits were obtained by gut microbiota transplantation from L-Fucose-treated pregnant females into OTA-exposed mothers. These findings suggest that inflammatory impact of OTA on maternal intestine/gut can pass to the fetus causing offspring ovary defects and support the use of L-Fucose as adjuvant to counteract the adverse effects of mycotoxins on the gut microbiota, particularly reference to those affecting reproductive organs.

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