Effects of the antimicrobial peptide WK3 on diarrhea, growth performance and intestinal health of weaned piglets challenged with enterotoxigenic Escherichia coli K88

Abstract

Background: Antibiotics are very effective for treating diarrhea in weaned pigs, but the global prohibition of antibiotics makes it urgent to find an alternative to antibiotics.
 Objective: An experiment was conducted to determine the antimicrobial activity of a linear trpzip-like β-hairpin antimicrobial peptide WK3 in vivo and to assess its effects on growth performance and intestinal health.
 Design: Thirty-two piglets were weaned at 21 days and housed in individual metabolic cages, which were randomly divided into four groups and were maintained on a corn-soybean meal-based basal diet. Group 1 included a blank group. Groups 2, 3, and 4 were orally infected by feeding with Enterotoxigenic Escherichia coli (ETEC) K88, which was followed by saline treatment (group 2), enrofloxacin injection at a dose of 2.5 mg/ kg (group 3), and WK3 injection at a dose of 2 mg/kg (group 4). The experiment lasted for 6 days, and feed and water were provided ad libitum.
 Results: Both WK3 and enrofloxacin effectively attenuated diarrhea and improved growth performance of piglets. Compared with the control group, WK3 significantly improved the villus height in the ileum (P < 0.05) but did not affect the villus height in the duodenum or jejunum. Additionally, we did not observe any obvious difference in crypt depth or villus height/crypt depth among the duodenum, jejunum and ileum (P > 0.05). WK3 also reduced the numbers of Enterococcus spp (P < 0.01) in the cecal contents, and the number of Enterobacterium spp tended to decrease (0.05 < P < 0.1). Moreover, the jejunal mucosa of the WK3 group exhibited lower interleukin-1α (IL-1a; P < 0.01), toll-like receptors-4 (TLR-4; P < 0.05), and myeloid differentiation primary response 88 (MyD88; P < 0.01) messenger ribonucleic acid (mRNA) expression levels. The jejunum of the WK3 group also exhibited an increased antioxidant capacity, reduced concentration of malondialdehyde (MDA; P < 0.05), and enhanced superoxide dismutase (SOD) activity (P < 0.05).
 Conclusions: WK3 has the potential to replace antibiotics as a new generation feed additive.

Review on Preventive Measures to Reduce Post-Weaning Diarrhoea in Piglets

“…The fed piglets Ceprocin AD had also higher levels of secretory IgA in the jejunum and of serum IgA and IgG compared with the control. The results on pro-inflammatory factors IL-1β and IL-6 were not in accordance with the effect seen in other studies, where reductions in pro-inflammatory cytokines are generally reported [ 223 , 224 , 228 , 229 ].…”

“…Unlike antibiotics, which target specific cellular activities (e.g., the synthesis of DNA, protein, or cell wall), AMPs target the lipopolysaccharide layer of cell membrane, which is ubiquitous in microorganisms [ 47 ]. Importantly, this makes it difficult for bacteria to develop resistance against these peptides, i.e., due to their ability to disrupt bacterial membranes via non-specific electrostatic interactions with the membrane lipid components [ 220 , 223 , 224 ]. Therefore, antimicrobial peptides may have potential as an alternative to antibiotics for use in livestock production.…”

“…Studies on the impact of AMPs on PWD in pigs are relatively new, with most published studies being conducted during the last decade. Zhang et al [ 224 ] injected chemically synthetised AMP WK3 (2 mg/kg body weight) to ETEC-F4-challenged piglets and measured a lower incidence of diarrhoea, higher growth performance, and higher villus height in the ileum than in the control group (ETEC-challenged) in a six-day-long study ( Table 8 ). WK3 also downregulated the expression of inflammatory factors, i.e., IL-1α, TLR-4, and MyD88, in jejunal mucosa, and increased the oxidative capacity in the jejunum, i.e., reduction in malondialdehyde concentrations and increase in total-superoxide dismutase activity.…”

Effects of Immobilized Antimicrobial Peptides on Growth Performance, Serum Biochemical Index, Inflammatory Factors, Intestinal Morphology, and Microbial Community in Weaning Pigs

“…This was also observed by previous studies, which found that adding compound AMPs in the diet improved the growth performance of piglets, thus increasing the effective utilization rate of feed and bringing more economic benefits to farmers ( 18 , 19 ). In addition, adding antimicrobial peptide WK3 in the diet attenuated diarrhea symptoms of ETEC K88 challenged pig models and improved growth performance of piglets ( 20 ). The results of this experiment are consistent with the results of the studies mentioned above, in which adding IAMPs in the diets of weaning piglets improved the growth performance and attenuated the diarrhea rate of piglets.…”

Risk factors associated with post-weaning diarrhoea in Austrian piglet-producing farms

“…Numerous feed additives have already been proposed as potential alternatives to ZnO (6,20). Feed additives, which potentially reduce the incidence of PWD include for example organic acids (39)(40)(41), probiotics (42)(43)(44)(45), prebiotics (46, 47), essential oils and other plant based substances (48, 49), exogenous enzymes (50,51), dehydrated porcine plasma (52), yeast (53) and antimicrobial peptides (54,55). However, while most studies on alternative strategies to reduce the usage of antimicrobial substances focus on feed additives, only a few studies report on the impact of management, housing conditions and biosecurity (56).…”