The K88 challenged and NA treated plus K88 challenged groups were administered 20 mL normal saline or 20 mL nicotinic acid solution once daily for 3 consecutive days. fourth day, the K88 and K88 + NA groups were treated with oral administration of 4 109cfu/mL ETEC K88. The results showed that NA alleviated the clinical symptoms of weaned piglets infected with ETEC K88. NA significantly reduced the amount of ETEC K88 in the spleen and liver (P< 0.05). The intestinal morphological damage caused by ETEC Myelin Basic Protein (68-82), guinea pig K88 contamination was alleviated by NA in weaned piglets. In addition, NA significantly alleviated the expression of inflammatory cytokine [Interleukin-6 (IL-6), Interleukin-8 (IL-8), tumor necrosis factor- (TNF-)] in the serum and intestines of weaned piglets infected with ETEC K88 (P< 0.05). NA Myelin Basic Protein (68-82), guinea pig significantly increased the content of secretory IgA (SIgA) and the expression of antimicrobial peptides [porcine defensin-2 (pBD2), protegrin1-5 (PG1-5) and PR39] in intestines of weaned pigs. NA increased the diversity of microflora in colonic contents, while NA significantly reduced the relative large quantity ofBacteroidetes, Bacteroidales, andBacteroidiain weaned piglets infected with ETEC K88 (P< 0.05). Furthermore, the NA group significantly reduced the level of HDAC7 in jejunum (P< 0.05) and increased the level of SIRT1 in the colon compared with the Control group. Moreover, NA significantly increased the levels phosphorylation of histone H3 at Ser10 (pH3S10) in ileum and the levels of acetylation of lysine 9 on histone 3 (acH3K9) and acH3K27 in colon (P< 0.05) in weaned piglets infected with ETEC K88 (P< 0.05). In conclusion, NA can alleviate the clinical symptoms, the damage of intestinal morphology, and intestinal inflammation in weaned piglets infected ETEC K88 through enhancing the expression of endogenous AMPs by associating the histone acetylation modification. Keywords:nicotinic acid, weaned piglets, ETEC, antibacterial peptides, HDACs == Graphical Abstract == Nicotinic acid could improve intestinal antimicrobial peptides to enhance resistance of weaned piglets toE. coliinfection by regulating intestinal microflora and its metabolites, histone deacetylase SIRT1 and HDAC7, modification sites such as acH3K9, acH3K27, and pH3S10 in the promoter region. == Introduction == Infants and other mammalian neonates often suffer from diarrhea Myelin Basic Protein (68-82), guinea pig during weaning, which is the leading killer of children under 5 years of age in developing countries all over the world (1,2). Studies have shown that this piglets are usually faced with some problems such as physical or mental disorders, changes in small intestinal structure, disturbed intestinal microbiota and diminished immune responses during weaning (3,4), which will easily lead to diarrheal disease caused by the invasion of varied pathogenic bacteria, enterotoxigenicE especially. coli(ETEC). ETEC post-weaning diarrhea, called as postweaning enteric colibacillosis also, is an essential factor leading to mortality of nursery pigs in the global swine creation. Chlamydia of ETEC in nursery pigs Myelin Basic Protein (68-82), guinea pig may stimulate diarrhea through the first one or two 14 days of postweaning intervals usually leading to dehydration, reduced putting on weight, and loss of life (5). Therefore, it is rather urgent to discover a good way to improve the condition level of resistance of weaned piglets. Nicotinic acidity (NA), referred to as Supplement B3 also, is Myelin Basic Protein (68-82), guinea pig among the most significant water-soluble B vitamin supplements in mammals, and used being a give food to additive in contemporary animal husbandry widely. Previous studies got proven that NA performed an important function in anti-pellagra and legislation of mobile energy fat burning capacity (6). As reported, nicotinamide treatment could ameliorate the span of bacterial and chemical substance induced colitis by improving MGC4268 neutrophil-specific antibacterial clearance (7). Whats even more, accumulating proof from mouse recommended that NA alleviated intestinal mucosal irritation and improved the appearance of endogenous antimicrobial peptides in intestinal epithelium (8). Endogenous antimicrobial peptides are a significant component of innate immunity in pets. Increasingly more evidence implies that antimicrobial peptides play an integral function in pathogen level of resistance and immune legislation (9,10). Nevertheless, you can find few studies in the system of NA regulating.