Curcumin mitigated aflatoxin B₁-induced endoplasmic reticulum stress and gut-kidney axis damage in sheep by...

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.

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.

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.