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

Background Aflatoxin B 1 (AFB 1 ), 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 AFB 1 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 1 -exposed sheep. Eighteen sheep were randomly divided into three treatment groups. The groups were the control group (CON, basal diet), the AFB 1 group (AFB 1 , basic diet + 500 μg/kg DM AFB 1 ), and the AFB 1 _Curcumin group (AFB 1 _CUR, basic diet + 500 μg/kg DM AFB 1 + 800 mg/kg DM curcumin) for 21 d. Results AFB 1 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 AFB 1 -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.