Department of Animal and Poultry Science, University of Guelph, Guelph, Canada.
J Nutr. 2010 Apr;140(4):806-11. doi: 10.3945/jn.109.114173. Epub 2010 Feb 10.
Stress and incomplete gastrointestinal development in early-weaned piglets represent significant challenges in commercial swine farming. Orally ingested recombinant epidermal growth factor (EGF) has been shown to remain biologically active in the gastrointestinal tract as well as stimulate intestinal development, reducing the incidence of pathogen infection and diarrhea. We have previously shown that the food-grade bacterium Lactococcus lactis can be genetically altered to express biologically active EGF when fed to early-weaned mice. In this study, we assigned 8 pigs to each of 4 groups that were given EGF-expressing L. lactis (EGF-LL), empty vector-expressing L. lactis (EV-LL), recombinant human EGF, or unsupplemented bacterial media, all of which were delivered as 50-mL i.g. doses twice per day. All pigs were killed after 14 d to examine intestinal morphology. Pigs in the EGF-LL group had greater jejunal and duodenal villus heights (P < 0.0001) and intestinal length (P = 0.049) than pigs in the control group. Immunohistochemistry with antibodies against proliferating cell nuclear antigen (PCNA) revealed that the proliferation of intestinal cells was significantly greater in the EGF-LL group than in the control group. PCNA expression and intestinal length also were greater in the EV-LL group, which received L. lactis that did not express EGF, than in the control group (P = 0.049), further supporting the use of naturally occurring intestinal microbes as desirable vectors for recombinant protein delivery. Our data demonstrates the feasibility of delivering a growth factor using common probiotic bacteria to farm animals for commercial practice.
早期断奶仔猪的应激和不完全胃肠道发育是商业养猪业面临的重大挑战。经口摄入的重组表皮生长因子（EGF）在胃肠道中仍保持生物活性，并刺激肠道发育，降低病原体感染和腹泻的发生率。我们之前已经表明，食用级细菌乳球菌 lactis 可以通过基因改造在早期断奶的小鼠中表达具有生物活性的 EGF。在这项研究中，我们将 8 头猪分配到 4 个组中，每组猪分别给予表达 EGF 的乳球菌（EGF-LL）、表达空载体的乳球菌（EV-LL）、重组人 EGF 或未补充细菌培养基，所有这些都以 50-mL 的剂量每天两次通过灌胃给予。所有猪在 14 天后被处死以检查肠道形态。EGF-LL 组的空肠和十二指肠绒毛高度（P < 0.0001）和肠道长度（P = 0.049）均大于对照组。用增殖细胞核抗原（PCNA）抗体进行的免疫组织化学染色显示，EGF-LL 组的肠细胞增殖明显大于对照组。EV-LL 组（接受未表达 EGF 的乳球菌）的 PCNA 表达和肠道长度也大于对照组（P = 0.049），这进一步支持利用天然存在的肠道微生物作为理想的重组蛋白传递载体。我们的数据证明了使用常见益生菌细菌向农场动物传递生长因子以进行商业实践的可行性。
