Taurine ameliorates deoxynivalenol-induced intestinal injury in piglets: Restoration of mitochondrial function linked to the PGC1α-NRF1/2 axis

Deoxynivalenol (DON) is a prevalent foodborne contaminant present in crops, posing significant risks to food safety and public health worldwide. Mitochondria, as the primary target of DON, play a crucial role in DON-mediated gastrointestinal toxicity. Taurine, a multifunctional nutrient, has been reported to exert antioxidant and anti-inflammatory effects by modulating mitochondrial function. However, whether taurine could alleviate intestinal injury by restoring mitochondrial function under DON exposure remains unclear. To address this knowledge gap, this study systematically investigated the potential protective effects of taurine on DON-induced intestinal damage in a piglet model. Twenty-four piglets were randomly assigned to four groups for 24 days: BD group (basal diet), DON group (3 mg/kg DON-contaminated diet), DON+LT group (DON diet with 0.3 % taurine), and DON+HT group (DON diet with 0.6 % taurine). Serum samples were collected for biochemical analysis, while jejunal tissues were examined for histology, barrier function, oxidative stress, inflammation, apoptosis, mitochondrial function, as well as related gene and protein expression. The results revealed that taurine effectively restored jejunal morphology disrupted by DON, as evidenced by increases in villus height/width and the villus height to crypt depth ratio. It preserved intestinal barrier integrity, reflected by reductions in diamine oxidase and D-lactate levels, alongside increased expression of genes and proteins related to intestinal mucus and mechanical barrier function. Furthermore, taurine mitigated intestinal oxidative stress by reducing reactive oxygen species, 8-hydroxydeoxyguanosine, and malondialdehyde levels, while enhancing antioxidant defenses. It also alleviated inflammation by suppressing pro-inflammatory cytokines and attenuated intestinal epithelial apoptosis through mitochondrial caspase-dependent and apoptosis-inducing factor-mediated pathways. Intriguingly, taurine improved the damaged mitochondrial structure and functionality within the intestinal epithelium irritated by DON. This improvement included enhanced respiratory chain complex activity, increased ATP levels, and mtDNA copy number. Additionally, taurine regulated gene expression related to mitochondrial respiration, fusion, fission, and autophagy. Simultaneously, taurine reversed the DON-induced inhibition of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α)-nuclear respiratory factor 1/2 (NRF1/2) axis, a critical pathway regulating mitochondrial biogenesis, respiratory function, and oxidative stress responses. Correlation analysis revealed significant associations between the PGC1α-NRF1/2 axis and mitochondrial function, as well as correlations with intestinal health parameters, including barrier function, redox status, inflammation, and apoptosis. In summary, this study provides the first evidence that dietary taurine supplementation effectively alleviates intestinal injury in DON-challenged piglets through mitochondrial restoration, which is strongly associated with the reactivation of the PGC1α-NRF1/2 axis. Our findings highlight the potential of mitochondrial-targeted therapies to mitigate gastrointestinal toxicity caused by the foodborne contaminant DON in both humans and animals.