Sodium butyrate mediates the MAPK signaling pathway and apoptosis and modulates intestinal flora to alleviate glycinin-induced intestinal injury in Cyprinus carpio

The study investigated the potential alleviating effect of sodium butyrate (SB) on intestinal injuries caused by glycinin in the diet of common carp. Fish were divided into six groups: a control group (without glycinin and SB), a Gly group (with glycinin), and four groups supplemented with different doses of SB (0.75, 1.50, 2.25, and 3.00 g/kg) based on the Gly group. All diets were isonitrogenous and isoenergetic, and the fish were fed these diets for 8 weeks. The results indicated that glycinin activated the mitogen-activated protein kinase (MAPK) signaling pathway, leading to upregulating ERK, JNK, and p38 gene expression in the intestine. However, SB2 and SB3 groups were able to inhibit this pathway. Furthermore, glycinin upregulated the expression of proapoptotic genes (Bax, Caspase-3, Caspase-8, and Caspase-9) while downregulating the antiapoptotic gene Bcl2. The SB2 and SB3 groups were found to alleviate glycinin-induced apoptosis. Additionally, dietary glycinin significantly decreased the expression of tight junction genes (ZO-1, Claudin3, Claudin7, and Occludin1) in the intestine, whereas the SB2 and SB3 groups improved intestinal barrier function. Glycinin also elevated serum levels of d-lactate, diamine oxidase, serotonin, and endothelin, resulting in intestinal damage and increased permeability. In contrast, the SB2 and SB3 groups reduced these serum levels, thereby regulating intestinal permeability. Moreover, glycinin disrupted the intestinal morphology, which was mitigated by the SB2 and SB3 groups by increasing the height and width of intestinal villi folds. Lastly, dietary glycinin altered the intestinal microecological balance by increasing Proteobacteria abundance and decreasing Clostridium and Bacteroidetes abundance. The SB2 and SB3 groups modulated the composition of dominant taxa by increasing Firmicutes and Acidobacteria abundance. Overall, SB was found to mediate the MAPK signaling pathway, apoptosis, upregulation of tight junction genes, maintenance of the intestinal physical barrier, and regulation of intestinal flora, thereby alleviating glycinin-induced intestinal damage.