Sulforaphane supplementation reprograms anti-oxidative genes via histone modifications in the ileum of weaning piglets

Currently, plant extracts are being extensively studied due to their anti-inflammatory and antioxidant properties. One is sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables. This study aimed to determine the effects of SFN supplementation on anti-oxidation genes in the ileum of weaned piglets from the perspective of histone modification. A total of 12 piglets [Duroc × (Landrace × Yorkshire)] with an initial body weight of 15 ± 0.5 kg (weaned at d 28) were randomly divided into two groups (n = 6 of each): the control group (CON, basal diet) and the SFN treatment group (SFN 1 g/kg + basal diet). The experiment period lasted for 30 d. The results showed that compared to CON, SFN supplementation could significantly increase the villus height of piglets' ileum (p < 0.05) but had no significant effects on crypt depth, villus width, and VH/CD of piglets' ileum. Additionally, the analysis of GSEA revealed that SFN upregulated signatures involving oxidative phosphorylation, anti-oxidative stress, fatty acid β-oxidation, and cell redox homeostasis pathways compared to CON. In addition, an increase in the mRNA expression of PPARα and mRNA expression levels of anti-oxidative genes NDUFB4, PRDX3, AIFM1, NDUFS8, GPX4, ETFDH, NDUFS2, IDH1, HTRA2, and FXN were significantly up-regulated in piglets supplemented SFN compared to CON. Finally, compared with the CON group, the histone activity markers H3K27ac, H3K18ac, H3K4me1, H3K4me2, and H3K18ac, as well as the genes and GPX4 and IDH1 target site PPARα activators of the SFN supplement group, were significantly up-regulated. We conclude that SFN-supplemented reprograms anti-oxidative genes via histone modifications in the ileum of weaning piglets.