Folic acid improves intestinal function in grass carp (Ctenopharyngodon idella): Revealing a new perspective of DNA methyltransferases and PP2A-p38 signaling pathway in intestinal epithelial function.

The beneficial effects of folic acid (FA) on intestinal barrier function are well recognized, however the underlying molecular mechanisms remain largely unexplored. This study aimed to investigate the effects of dietary FA on intestinal epithelial function in grass carp, and to reveal the potential molecular mechanism. The total of 450 healthy grass carp (686.83 ± 1.31 g) were randomly divided into 6 groups (18 barrels, 25 fish per barrel), and fed diets containing levels of FA (0.57, 1.11, 1.53, 2.08, 2.64, and 3.15 mg/kg diet) for 8 weeks. The results showed that, compared with the control group, a dietary FA level of 1.11 mg/kg significantly significantly increased FBW, PWG, WG, SGR and FI, as well as FA and methionine cycling in grass carp (P < 0.05). Dietary FA also promoted the intestinal barrier function and proliferation of intestinal epithelial cells (P < 0.05). Further, dietary FA increased the protein levels of the DNA methyltransferase (DNMT) family and the protein phosphatase 2A (PP2A)-p38 signaling pathway was significantly activated in fish fed the 1.11 mg/kg FA diet (P < 0.05). In conclusion, dietary FA improved intestinal epithelial function in grass carp by modulating the expression of DNMTs and activating the PP2A-p38 signaling pathway. Based on percent weight gain, the optimal requirement of FA for sub-adult grass carp (686.8-1264.7 g) was estimated to be 1.03 mg/kg.