Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, United States of America.
PLoS One. 2013 Apr 24;8(4):e59838. doi: 10.1371/journal.pone.0059838. Print 2013.
The clinical onset and severity of intestinal disorders in humans and animals can be profoundly impacted by early life stress. Here we investigated the impact of early weaning stress in pigs on intestinal physiology, clinical disease, and immune response to subsequent challenge with enterotoxigenic F18 E. coli (ETEC).
Pigs weaned from their dam at 16 d, 18 d, and 20 d of age were given a direct oral challenge of F18 ETEC at 26 d of age. Pigs were monitored from days 0 to 4 post-infection for clinical signs of disease. On Day 4 post-ETEC challenge, ileal barrier function, histopathologic and inflammatory cytokine analysis were performed on ileal mucosa.
Early weaned pigs (16 d and 18 d weaning age) exhibited a more rapid onset and severity of diarrhea and reductions in weight gain in response to ETEC challenge compared with late weaned pigs (20 d weaning age). ETEC challenge induced intestinal barrier injury in early weaned pigs, indicated by reductions in ileal transepithelial electrical resistance (TER) and elevated FD4 flux rates, in early weaned pig ileum but not in late weaned pigs. ETEC-induced marked elevations in IL-6 and IL-8, neutrophil recruitment, and mast cell activation in late-weaned pigs; these responses were attenuated in early weaned pigs. TNF levels elevated in ETEC challenged ileal mucosa from early weaned pigs but not in other weaning age groups.
These data demonstrate the early weaning stress can profoundly alter subsequent immune and physiology responses and clinical outcomes to subsequent infectious pathogen challenge. Given the link between early life stress and gastrointestinal diseases of animals and humans, a more fundamental understanding of the mechanisms by which early life stress impacts subsequent pathophysiologic intestinal responses has implications for the prevention and management of important GI disorders in humans and animals.
人类和动物的肠道疾病的临床发病和严重程度可能会受到早期生活压力的深刻影响。在这里，我们研究了早期断奶应激对仔猪肠道生理、临床疾病和对后续肠毒素性 F18 大肠杆菌（ETEC）挑战的免疫反应的影响。
16、18 和 20 日龄断奶的仔猪在 26 日龄时直接口服 ETEC F18 进行挑战。在感染后 0 至 4 天对仔猪进行监测，以观察疾病的临床症状。在 ETEC 挑战后 4 天，对回肠黏膜进行回肠屏障功能、组织病理学和炎症细胞因子分析。
与晚断奶仔猪（20 日龄断奶）相比，早期断奶仔猪（16 日龄和 18 日龄断奶）在 ETEC 挑战后表现出更快的发病和腹泻严重程度，以及体重增长减少。ETEC 挑战诱导早期断奶仔猪的回肠屏障损伤，表现为回肠上皮跨膜电阻（TER）降低和 FD4 通量率升高，但在晚断奶仔猪中没有这种情况。ETEC 诱导的 IL-6 和 IL-8、中性粒细胞募集和肥大细胞活化在晚断奶仔猪中明显升高；这些反应在早期断奶仔猪中被减弱。TNF 水平在 ETEC 挑战的早期断奶仔猪回肠黏膜中升高，但在其他断奶年龄组中没有升高。
这些数据表明，早期断奶应激可以深刻改变随后对感染性病原体挑战的免疫和生理反应以及临床结果。鉴于早期生活应激与动物和人类胃肠道疾病之间的联系，更深入地了解早期生活应激影响随后肠道病理生理反应的机制，对于预防和管理人类和动物的重要胃肠道疾病具有重要意义。
