In the swine industry, subtherapeutic doses of in-feed antibiotics used to be commonly added to the diet at post-weaning period to prevent infectious diseases and promote growth performance of weaned pigs. However, the new restriction of using antibiotics as a growth promoter increases the importance of other nutritional strategies for the maintenance of animal health and production. In addition, growing evidence suggests that exposure to trace amounts of antibiotics might delay the growth and development of young animals and humans and delay recovery from diseases. Therefore, three studies were conducted (1) to investigate the potential detrimental effects of trace amounts of antibiotics, and (2) to explore the efficacy of dietary supplementation of an oligosaccharide-based polymer on weanling pigs’ growth performance, systemic immunity, intestinal health, serum and intestinal metabolome, and intestinal microbiome using a disease challenge model. The first study evaluated the impacts of trace amounts of antibiotic (0.5 mg/kg of carbadox added to the nursery basal diet) on growth performance, diarrhea condition, systemic immunity, and intestinal health of weaned pigs experimentally infected with enterotoxigenic E. coli (ETEC) F18. Pigs supplemented with the label-recommended dose of antibiotic (50 mg/kg of carbadox to the nursery basal diet) had greater (P < 0.05) final body weightand lower (P < 0.05) overall frequency of diarrhea, compared with pigs in the control and trace amounts of antibiotics groups. Pigs supplemented with trace amounts of antibiotics had the lowest (P < 0. 05) average daily gain and feed efficiency from day (d) 0 to 5 post-inoculation (PI) and had the highest (P < 0.05) percentage of β-hemolytic coliforms in fecal samples on d 2 and 5 PI, compared with pigs in the other two groups. Pigs fed with trace amounts of antibiotics had greater (P < 0.05) neutrophils and neutrophil:lymphocyte ratio, but lower (P < 0.05) lymphocytes and monocytes on d 2 PI, compared with pigs in the label-recommended dose of antibiotic group. Pigs fed with trace amounts of antibiotic had the greatest (P < 0.05) serum C-reactive protein on d 2 and d 5 PI and serum TNF-α on d 5 PI, compared with pigs in the other groups. Pigs in the label-recommended dose of antibiotic group had lower (P < 0.05) serum haptoglobin than pigs in the other groups on d 2, 5, and 11 PI. Pigs fed with label-recommended dose of antibiotic had increased (P < 0.05) mRNA expression of ZO-1 and OCDN, and reduced (P < 0.05) IL1B, IL6, and TNFA in ileal mucosa on d 5 PI, compared with control. However, trace amounts of antibiotic upregulated (P < 0.05) mRNA expression of IL1B, IL6, and PTGS2 in ileal mucosa on d 11 PI, compared with the label-recommended dose of antibiotic group. The first study indicates that trace amounts of antibiotic supplementation exacerbated the detrimental effects of ETEC infection and delayed the recovery of pigs. The second study was a continuation of the first study, where we explored the impacts of trace amounts of antibiotic on metabolomic profiles and colon microbiota of ETEC F18-challenged pigs. Differences in the metabolic profiles of serum and colon digesta, and microbial profiles of colon digesta were found between pigs supplemented with trace amounts of antibiotic and label-recommended dose of antibiotic, especially during the peak infection period (d 5 PI). Supplementation of trace amounts of antibiotic up- or down-regulated serum and colon digesta metabolites associated with amino acids, carbohydrates, and purine metabolism on d 5 PI, from those of pigs in the label-recommended dose of antibiotic group. Pigs fed with label-recommended dose of antibiotic had the highest (P < 0.05) relative abundance of Lactobacillaceae and tended to have greater (P < 0.1) relative abundance of Lachnospiraceae in the colon digesta on d 5 PI. On d 11 PI, pigs with the label-recommended dose of antibiotic had increased (P < 0.05) relative abundance of Clostridiaceae compared with other groups and had reduced (P < 0.05) relative abundance of Prevotellaceae compared to pigs in the control group. The second study indicated that trace amounts of antibiotic modified metabolites and metabolic pathways that may be associated with its deleterious effects on ETEC F18 infection. Furthermore, the altered gut microbiota profiles by label-recommended dose of antibiotic administration may promote beneficial gut microorganisms and disease resistance in pigs. The third study was conducted to investigate the efficacy of dietary supplementation of an oligosaccharide-based polymer (Coligo) on growth performance, diarrhea severity, intestinal health, and systemic immunity of weaned pigs infected with ETEC F18 when compared with a label-recommended dose of antibiotic treatment. Pigs in the antibiotic or Coligo groups had greater (P < 0.05) body weight on d 5 or d 11 PI than pigs in the control group, respectively. Supplementation of antibiotic or Coligo enhanced (P < 0.05) feed efficiency from d 0 to 5 PI and reduced (P < 0.05) frequency of diarrhea throughout the experiment, compared with pigs in the control group. Pigs fed with antibiotic or Coligo had reduced (P < 0.05) neutrophil counts and serum haptoglobin concentration compared to pigs in control group on d 2 and 5 PI. Supplementation of Coligo reduced (P < 0.05) total coliforms in mesenteric lymph nodes on d 5 and 11 PI, whereas pigs in the antibiotic or Coligo group had lower (P < 0.05) numbers of total coliforms in the spleen on d 11 PI compared with pigs in the control group. On d 5 PI, pigs fed Coligo had greater (P < 0.05) gene expression of ZO1 in jejunal mucosa, but less (P < 0.05) mRNA expression of IL1B, IL6, and TNF in ileal mucosa, in comparison to control pigs. Supplementation with antibiotic enhanced (P < 0.05) the gene expression of OCLN in jejunal mucosa but decreased (P < 0.05) IL1B and IL6 gene expression in ileal mucosa compared with the pigs in the control group. On d 11 PI, pigs in the antibiotic or Coligo group had upregulated (P < 0.05) gene expression of CLDN1 in jejunal mucosa, but Coligo reduced (P < 0.05) IL6 gene expression in ileal mucosa compared to the control group. The third study suggests that supplementation of Coligo has the potential to replace antibiotics to enhance disease resistance and promote growth performance of weaned pigs under disease challenge conditions. In summary, trace amounts of antibiotic evaluated in the present studies have shown detrimental effects on growth performance and disease resistance of pigs challenged with ETEC F18, potentially by exacerbating systemic inflammation and altering metabolic and microbial profiles. An oligosaccharide-based polymer exhibited beneficial effects on growth performance and disease resistance of pigs challenged with ETEC F18 by alleviating local and systemic inflammation and improving intestinal health.
