College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
ZJU-Xinchang Joint Innovation Centre (TianMu Laboratory), Gaochuang Hi-Tech Park, Shaoxing 312500, China.
Int J Mol Sci. 2024 Sep 11;25(18):9826. doi: 10.3390/ijms25189826.
Itaconic acid (IA) is recognized for its potential application in treating intestinal diseases owing to the anti-inflammatory and antioxidant properties. Perfluorooctanoic acid (PFOA) can accumulate in animals and result in oxidative and inflammatory damages to multi-tissue and organ, particularly in the intestinal tract. This study aimed to explore whether IA could mitigate intestinal damage induced by PFOA exposure in laying hens and elucidate its potential underlying mechanisms. The results showed that IA improved the antioxidant capacity of laying hens and alleviated the oxidative damage induced by PFOA, as evidenced by the elevated activities of T-SOD, GSH-Px, and CAT, and the decreased MDA content in both the jejunum and serum. Furthermore, IA improved the intestinal morphological and structural integrity, notably attenuating PFOA-induced villus shedding, length reduction, and microvillus thinning. IA also upregulated the mRNA expression of , , , and in the jejunum, thereby restoring intestinal barrier function. Compared with the PF group, IA supplementation downregulated the gene expression of and upregulated the , , , and expression in the jejunum. Meanwhile, the PF + IA group exhibited lower expressions of inflammation-related genes (, , , , and ) compared to the PF group. Moreover, IA reversed the PFOA-induced imbalance in gut microbiota by reducing the harmful bacteria such as , , and , while increasing the abundance of beneficial bacteria like . Correlation analysis further revealed a significant association between gut microbes, inflammatory factors, and the Keap1/Nrf2/HO-1 pathway expression. In conclusion, dietary IA supplementation could alleviate the oxidative and inflammatory damage caused by PFOA exposure in the intestinal tract by reshaping the intestinal microbiota, modulating the Keap1/Nrf2/HO-1 pathway and reducing oxidative stress and inflammatory response, thereby promoting intestinal homeostasis.
衣康酸（IA）因其具有抗炎和抗氧化特性而被认为有潜力用于治疗肠道疾病。全氟辛酸（PFOA）可在动物体内蓄积，并导致多组织和器官的氧化和炎症损伤，尤其是在肠道中。本研究旨在探讨 IA 是否能减轻 PFOA 暴露对蛋鸡肠道的损伤，并阐明其潜在的作用机制。结果表明，IA 提高了蛋鸡的抗氧化能力，缓解了 PFOA 引起的氧化损伤，表现在空肠和血清中 T-SOD、GSH-Px 和 CAT 的活性升高，MDA 含量降低。此外，IA 改善了肠道形态和结构的完整性，显著减轻了 PFOA 引起的绒毛脱落、变短和微绒毛变薄。IA 还上调了空肠中 、 、 、 等基因的表达，从而恢复了肠道屏障功能。与 PF 组相比，IA 补充剂下调了 基因的表达，上调了空肠中 、 、 、 等基因的表达。同时，PF + IA 组的炎症相关基因（ 、 、 、 、 ）的表达低于 PF 组。此外，IA 通过减少有害菌（如 、 、 ）的丰度，增加有益菌（如 ）的丰度，从而逆转了 PFOA 引起的肠道微生物失衡。相关性分析进一步表明，肠道微生物、炎症因子与 Keap1/Nrf2/HO-1 通路表达之间存在显著关联。总之，日粮 IA 补充可通过重塑肠道微生物群、调节 Keap1/Nrf2/HO-1 通路以及减轻氧化应激和炎症反应，缓解 PFOA 暴露引起的肠道氧化和炎症损伤，从而促进肠道稳态。
