Early Weaning Stress in Pigs Impairs Innate Mucosal Immune Responses to Enterotoxigenic E. coli Challenge and Exacerbates Intestinal Injury and Clinical Disease

Abstract

Background and AimsThe 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).MethodologyPigs 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.ResultsEarly 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.ConclusionsThese 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.

Effects of probiotics on growth performance, blood parameters, and antibody stimulation in piglets

“…However, physiological and/or psychological stresses such as weaning lead to dysfunctional of gut microbial composition (McLamb et al, 2013). By supplementing probiotics to the piglets feeding during post weaning, there is a potential to modulate intestinal microbial diversity by improving the establishment of beneficial bacterial populations for health and reducing pathogenic bacteria such as enterotoxigenic E. coli (Brousseau, et al, 2015).…”

Escherichia coli lipopolysaccharide affects intestinal mucin secretion in weaned pigs

“…coli LPS induces morphological and histological changes in the intestine of weaned piglets, such as: atrophy of villi, increase in crypt depth, and injury to the epithelial barrier (Ospina et al ., 2011;Parra et al ., 2011;Montoya et al ., 2012;McLamb et al ., 2013). LPS also induces morphological changes in goblet cells, which cause variations in their proliferative activity in different organs (Shimizu et al, 2011).…”

Potent immune responses induced by aSalmonellaghost delivery system that expresses the recombinant Stx2eB, FedF, and FedA proteins of theEscherichia coli-producing F18 and Shiga toxin in a murine model and evaluation of its protective effect as a porcine vaccine candidate

“…Although current vaccine developments against ED have concentrated on antitoxin and anticolonization immunity, CMI still plays a pivotal role in providing protection against ED during post-weaning (Haesebrouck et al 2004;McLamb et al 2013). In this study, we observed an increased SI (Figure 4(IV)) and a significant elevation of INF-g ( Figure 5), which is a marker of CMI in the splenic T cell, of primed mice that were individually pulsed with Stx2eB, FedF, and FedA.…”