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Background <p>Aflatoxin B<sub>1</sub> (AFB<sub>1</sub>), a toxic secondary metabolite produced by <i>Aspergillus flavus</i> and <i>Aspergillus parasiticus</i>, is widely present in various crops and induces endoplasmic reticulum stress in the intestine and kidney of animals, leading to apoptosis and inflammatory damage. Curcumin is a natural phenolic antioxidant that has antioxidant, anti-apoptotic and anti-inflammatory effects. However, the role and mechanism of curcumin in alleviating the toxicity of AFB<sub>1</sub> in sheep remain unclear. Therefore, this study aimed to investigate the mitigating effects of curcumin on intestinal microbiota disorders and intestinal and kidney injuries in AFB<sub>1</sub>-exposed sheep. Eighteen sheep were randomly divided into three treatment groups. The groups were the control group (CON, basal diet), the AFB<sub>1</sub> group (AFB<sub>1</sub>, basic diet + 500&#xa0;μg/kg DM AFB<sub>1</sub>), and the AFB<sub>1</sub>_Curcumin group (AFB<sub>1</sub>_CUR, basic diet + 500&#xa0;μg/kg DM AFB<sub>1</sub> + 800&#xa0;mg/kg DM curcumin) for 21&#xa0;d.</p> Results <p>AFB<sub>1</sub> induced intestinal barrier dysfunction, intestinal flora imbalance, and intestinal mucosal damage. Curcumin addition inhibited the activity of the ATF6/GRP78 and IL-1β/NF-κB signaling pathways to alleviate kidney injury and activated the NRF2/KEAP1 pathway and antioxidant system to reduce the toxic substances cycle in the intestine-kidney axis (<i>P</i> &lt; 0.05). The protective effects of curcumin on the intestine and kidney are related to a reduction in the levels of <i>Prevotella</i>&#xa0;<i>ruminicola</i> and <i>Ruminococcus</i>&#xa0;<i>albus</i>. Therefore, the structure of the microbiota and antioxidant functions were improved, mitigating damage to the intestine-kidney axis.</p> Conclusions <p>Curcumin can alleviate AFB<sub>1</sub>-induced disorder of the intestinal microbiota by enhancing intestinal barrier function; reducing intestinal apoptosis, oxidative stress, and inflammatory damage; and regulating the intestinal microbiota via the intestine-kidney axis. Moreover, the activity of the ATF6/GRP78 and IL-1β/NF-κB signaling pathways was inhibited by curcumin to mitigate intestine-kidney axis injury. Additionally, activating the NRF2/KEAP1 signaling pathway promotes the function of biological antioxidant system.</p>

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Curcumin mitigated aflatoxin B1-induced endoplasmic reticulum stress and gut-kidney axis damage in sheep by regulating the ATF6/GRP78 and IL-1β/NF-κB signaling pathways

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月21日

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  • Ting Wang,
  • Chuanqi Wang,
  • Tongwei Liu,
  • Jiefeng Li,
  • Hengtong Fang,
  • Jing Zhang

摘要

Background

Aflatoxin B1 (AFB1), a toxic secondary metabolite produced by Aspergillus flavus and Aspergillus parasiticus, is widely present in various crops and induces endoplasmic reticulum stress in the intestine and kidney of animals, leading to apoptosis and inflammatory damage. Curcumin is a natural phenolic antioxidant that has antioxidant, anti-apoptotic and anti-inflammatory effects. However, the role and mechanism of curcumin in alleviating the toxicity of AFB1 in sheep remain unclear. Therefore, this study aimed to investigate the mitigating effects of curcumin on intestinal microbiota disorders and intestinal and kidney injuries in AFB1-exposed sheep. Eighteen sheep were randomly divided into three treatment groups. The groups were the control group (CON, basal diet), the AFB1 group (AFB1, basic diet + 500 μg/kg DM AFB1), and the AFB1_Curcumin group (AFB1_CUR, basic diet + 500 μg/kg DM AFB1 + 800 mg/kg DM curcumin) for 21 d.

Results

AFB1 induced intestinal barrier dysfunction, intestinal flora imbalance, and intestinal mucosal damage. Curcumin addition inhibited the activity of the ATF6/GRP78 and IL-1β/NF-κB signaling pathways to alleviate kidney injury and activated the NRF2/KEAP1 pathway and antioxidant system to reduce the toxic substances cycle in the intestine-kidney axis (P < 0.05). The protective effects of curcumin on the intestine and kidney are related to a reduction in the levels of Prevotella ruminicola and Ruminococcus albus. Therefore, the structure of the microbiota and antioxidant functions were improved, mitigating damage to the intestine-kidney axis.

Conclusions

Curcumin can alleviate AFB1-induced disorder of the intestinal microbiota by enhancing intestinal barrier function; reducing intestinal apoptosis, oxidative stress, and inflammatory damage; and regulating the intestinal microbiota via the intestine-kidney axis. Moreover, the activity of the ATF6/GRP78 and IL-1β/NF-κB signaling pathways was inhibited by curcumin to mitigate intestine-kidney axis injury. Additionally, activating the NRF2/KEAP1 signaling pathway promotes the function of biological antioxidant system.