Effects And Mechannism Of Butyrate On Disease Resistant In Piglets

Butyrate, a major species of short-chain fatty acid (SCFA) produced by bacterial fermentation of undigested carbohydrates. Butyrate has been used to treat different inflammatory disease with positive outcomes, the mechanisms by which butyrate exerts its anti-inflammatory effects remain largely undefined. Here we proposed a new mechanism that butyrate manipulate endogenous AMPs which contributes to the elimination of E. coli O157:H7, and thus affects the alleviation of inflammation, furthermore, the mechanisms underlying butyrate-induced AMP gene expression were also examined. The main results were shows as following.1. Effects of NaB on E. coli O157:H7 infection in pigletsNaB can alleviate the decrease of growth performance, intestinal inflamation, damage of intestinal morphology and barrier function caused by E. coli O157:H7 infection and NaB can also upregulte AMPs expression and enhance disease resistant in piglest. ①NaB alleviates clinical symptoms caused by E. coli O157:H7 infection. E. coli O157:H7-challenged piglets developed clinical signs of disease, including loss of appetite, ruffled fur, decreased ADFI and ADG, decreased activity and lethargy, and kidney damage, while NaB alleviates clinical symptoms caused by E. coli O157:H7 infection. ■ NaB reduces E. coli O157:H7 counts in feces. ③ NaB alleviate the damage of intestinal morphology and barrier function caused by E. coli O157:H7 infection. E. coli O157:H7-challenged piglets cause damage of intestinal morphology and barrier function, increasing the concentration of DLA and DAO, while NaB alleviate the damage of intestinal morphology and barrier function caused by E. coli O157:H7 infection.④ Dietary NaB can prevent E. coli O157:H7-induced increases in serum concentrations of IL-6, IL-1β, TNF-a, IgA, and IgG, and decrease infiltration of macrophages and neutrophils. ⑤ NaB stimulates AMP gene expression. NaB treatment significantly upregulated pBD2 and pBD3 gene expression in the ileum and colon compared with control.2. Mechanisms underlying NaB enhanced disease resistant of pigletsNaB enhances antibacterial activity and bacterial clearance of macrophage cells and alleviates inflammation caused by E. coli O157:H7 infection by inducing endogenous antimicrobial peptides. we use macrophage 3D4/2 cells as a model to evaluate effects of NaB on the function against E. coli O157:H7.① NaB concentrations (256 or 512 mmol/L) can kill or inhibit bacterial growth in vitro.② NaB upregulates endogenous AMPs in 3D4/2 cells in a dose-dependent manner, and an obvious time-dependent induction of pBD2, pBD3, PG1-5, PMAP37 and PR-39. ③ NaB enhances antibacterial activity and bacterial clearance of 3D4/2 cells.④ NaB alleviate inflammation caused by E. coli O157:H7 infection.NaB enhances antibacterial activity of IPEC-1 cells by inducing endogenous antimicrobial peptides and NaB can also enhances barrier function of epithelial cells, leading to augment of function against E. coli O157:H7 adhesion and invasion. ① NaB treatment upregulates pBD2 and pBD3 expression in IPEC-1 in a dose-dependent. ② NaB enhances antibacterial activity of IPEC-1 with antimicrobial peptide upregulated. ③ NaB enhances barrier function Treatment with NaB 24 h significantly increases TER values, which indicates that NaB enhances epithelial barrier function in IPEC-1 cells. Further, the results shows that pretreatment with NaB for 24 h obviously prevented the E. coli O157:H7-induced decreases of TER and tight junction protein sythesis of ZO-1 and Occludin in IPEC-1 cells.④ NaB enhances function against E. coli O157:H7 adhesion and invasion in epithelial cells.Taken together, we can conclude that NaB enhances antibacterial activity and bacterial clearance of macrophage and IPEC-1 cells by inducing endogenous antimicrobial peptides. NaB can also enhances barrier function of epithelial cells, leading to augment of function against E. coli O157:H7 adhesion and invasion.3. Mechanisms underlying NaB-induced antimicrobial peptideNaB treatment augments antibacterial activity and bacterial clearance, leading to amelioration of inflammation, and that these effects are likely due to the induction of endogenous synthesis of AMPs. We use 3D4/2 cells as a model to investigate the mechanisms underlying NaB-induced antimicrobial peptide.① NaB inhibits histone deacetylase (HDAC) activity and increases histone acetylation in 3D4/2 cells.② HDAC inhibitor upregulates 9 AMP genes including pBD2, pBD3, PG1-5, PMAP37 and PR39 whereas HAT inhibitor downregulates these AMP genes expression. ③NaB upregulates endogenous AMPs via HDAC inhibition. ④ NaB augments the antibacterial activity and bacterial clearance of 3D4/2 cells, leading to an amelioration of the inflammation, which is likely due to induction of the endogenous synthesis of AMPs.In summary, we concluded that butyrate, a natural product of digestion, can be administered to induce endogenous antimicrobial peptide, which, in turn, enhances disease resistant of piglets. This strategy for treatment of E. coli O157:H7 has a potential to be used in farm animals and human as possible alternatives to conventional antibiotics.