Alginate-encapsulated enzymes mitigate deoxynivalenol-induced hepatic mitochondrial dysfunction and glycolithocholic acid accumulation in piglets.

BACKGROUND: Deoxynivalenol (DON), a mycotoxin commonly found in grains and feed, poses a serious threat to animal and public health. This study aimed to investigate the underlying mechanisms of DON-induced liver damage in piglets and to elucidate the potential of alginate-encapsulated enzyme in mitigating hepatotoxicity in vivo.

RESULTS: The results indicated that DON exposure induced growth retardation and hepatic mitochondrial damage in piglets, which were effectively rescued by DON-degrading enzymes (DDE) supplementation. Hepatic transcriptomic profiling revealed that DON induced downregulation of oxidative phosphorylation‑related genes and ATP-binding cassette subfamily B member 4 (ABCB4), accompanied by the upregulation of the chemokine CCL21 and the adhesion molecule VCAM1. In contrast, no downregulation of oxidative phosphorylation‑related genes or aberrant expression of the aforementioned factors was observed in the DDE treatment group. Meanwhile, DON promotes T cell recruitment and their differentiation into the pro-inflammatory Th17 subset by inducing NF-κB-mediated expression of IL-1β and CCL21, thereby amplifying the inflammatory response. Further analysis revealed that DON exposure induced metabolic dysfunction of lysophospholipids and glycolithocholic acid (GLCA) in the liver and suppressed farnesoid X receptor (FXR) expression. Mechanistically, the downregulation of ABCB4 by DON was associated with reduced expression of PPARγ coactivator-1α (PGC-1α) and FXR, suggesting a potential link involving the PGC-1α/FXR axis. This downregulation results in the accumulation of GLCA, thereby exacerbating hepatic damage. Notably, alginate-encapsulated DDE effectively reversed the DON-induced GLCA metabolic dysfunction and the Th17 immune response.

CONCLUSIONS: Alginate-encapsulated DDE effectively mitigated DON-induced hepatic mitochondrial damage, T cell enrichment, and impaired bile acid metabolism in piglets. This study suggests a potential ABCB4‑dependent mechanism underlying DON-induced hepatotoxicity and provides a promising enzymatic strategy for mitigating DON contamination in vivo. However, further studies are required to clarify the potential mechanism of DON-induced hepatotoxicity.