文献类型： 外文期刊

作者： Jin, Shunshun ¹ ; Wu, Jian ² ; Wang, Chenyu ¹ ; He, Yiwen ¹ ; Tang, Yulong ² ; Huang, Le ² ; Zhou, Hui ¹ ; Liu, Di ⁵ ; Wu, Ziping ⁴ ; Feng, Yanzhong ⁵ ; Chen, Heshu ⁵ ; He, Xinmiao ¹ ; Yang, Guan ⁶ ; Peng, Can ² ; Qiu, Jiazhang ⁷ ; Li, Tiejun ² ; Yin, Yulong ² ; He, Liuqin ¹ ;

作者机构： 1.Hunan Normal Univ, Hunan Prov Key Lab Anim Intestinal Funct & Regulat, Hunan Int Joint Lab Anim Intestinal Ecol & Hlth, Lab Anim Nutr & Human Hlth,Coll Life Sci, Changsha 410081, Peoples R China

2.Chinese Acad Sci, Inst Subtrop Agr, Key Lab Agroecol Proc Subtrop Reg, Hunan Prov Key Lab Anim Nutr Physiol & Metab Proc, Changsha 410125, Peoples R China

3.Univ Manitoba, Dept Anim Sci, Winnipeg, MB R3T2N2, Canada

4.Queens Univ Belfast, Agr & Food Econ, Belfast BT95PX, North Ireland

5.Heilongjiang Acad Agr Sci, Harbin 150086, Peoples R China

6.City Univ Hong Kong, Dept Infect Dis & Publ Hlth, Kowloon, Hong Kong 999077, Peoples R China

7.Jilin Univ, Coll Vet Med, State Key Lab Diag & Treatment Severe Zoonot Infec, Key Lab Zoonosis Res,Minist Educ, Changchun 130025, Peoples R China

8.Yuelushan Lab, 246 Hongqi Rd, Changsha 410128, Peoples R China

关键词： aspartate; microbiota; oxidative stress; RIP pathway

期刊名称：ADVANCED SCIENCE （ 影响因子：14.1； 五年影响因子：15.6 ）

ISSN：

年卷期： 2025 年 12 卷 11 期

页码：

收录情况： SCI

摘要： Aspartate (Asp) metabolism-mediated antioxidant functions have important implications for neonatal growth and intestinal health; however, the antioxidant mechanisms through which Asp regulates the gut microbiota and influences RIP activation remain elusive. This study reports that chronic oxidative stress disrupts gut microbiota and metabolite balance and that such imbalance is intricately tied to the perturbation of Asp metabolism. Under normal conditions, in vivo and in vitro studies reveal that exogenous Asp improves intestinal health by regulating epithelial cell proliferation, nutrient uptake, and apoptosis. During oxidative stress, Asp reduces Megasphaera abundance while increasing Ruminococcaceae. This reversal effect depends on the enhanced production of the antioxidant eicosapentaenoic acid mediated through Asp metabolism and microbiota. Mechanistically, the application of exogenous Asp orchestrates the antioxidant responses in enterocytes via the modulation of the RIP3-MLKL and RIP1-Nrf2-NF-kappa B pathways to eliminate excessive reactive oxygen species and maintain mitochondrial functionality and cellular survival. These results demonstrate that Asp signaling alleviates oxidative stress by dynamically modulating the gut microbiota and RIP-dependent mitochondrial function, providing a potential therapeutic strategy for oxidative stress disease treatment.