The intestinal mucosa contributes to homeostasis by preventing the entrance of biological and chemical agents across the epithelium that could alter the stability of the system. This protective function is especially important at the time of weaning, when animals are exposed to infectious agents and to numerous stresses such as the change of environment and diet. Diets supplemented with spray-dried plasma or plasma protein fractions have been shown to improve growth performance of farm animals and have been proposed as an alternative to antibiotics. In this review, we summarize our findings on the mechanism of action of dietary plasma proteins using a rat model of intestinal inflammation, based on the administration of Staphylococcus aureus enterotoxin B (SEB). Staphylococcal enterotoxin B activates the gut-associated lymphoid tissue (GALT), increasing T-lymphocytes in Peyer's patches and the number of activated T lymphocytes in mesenteric lymph nodes (organized GALT). In the lamina propria SEB increased cytotoxic T gammadelta and natural killer cell populations of the diffuse GALT. Staphyloccocal enterotoxin B significantly increased proinflammatory cytokines in Peyer's patches and mucosa. Plasma protein supplements modulated the mucosal immune response in organized and diffuse GALT, protecting GALT from possible excessive activation by the SEB challenge. These effects are accompanied by a reduction of proinflammatory cytokine production, supporting the view that changes in cytokine production mediate the effects of dietary plasma proteins during intestinal inflammation. The increase in mucosal permeability and intestinal secretion induced by SEB was associated with decreased expression of mucosal tight-junction and adherent-junction proteins. Both plasma and plasma protein fractions prevented the effects of SEB on intestinal permeability, thus reducing the exposure of the host to microbial and food antigens across the interstitial space. These findings indicate that dietary plasma proteins modulate functional and structural properties of the intestinal mucosa.
The use of growth promoting and therapeutic antibiotics in piglet feed has been a concerning subject over the last few decades because of the risk of generating antimicrobial resistance that could be transferred to humans. As a result, many products have been proposed as potential alternatives to the use of antibiotics, and among these, spray dried plasma is considered one of the most promising. However, there have been concerns about its biosafety, particularly during periods of emergence or re-emergence of swine diseases in different regions of the world, such as the recent porcine epidemic diarrhea virus outbreak in North America. The objectives of this paper are to review recent publications about the use of spray dried plasma as an alternative to antibiotics in weaned pig diets, the possible mechanisms of action of spray dried plasma, and the existing evidence related to the biosafety of spray dried animal plasma. Particular attention is given to studies in which spray dried plasma has been directly compared to antibiotics or other alternative antimicrobial products. Several studies on the possible modes of action for spray dried plasma, such as preservation of gut barrier function or modulation of the immune response, are also reviewed. Finally, the paper focuses on the review of the existing studies on the risks of disease transmission with the use of spray dried plasma from porcine origin. Overall, spray dried plasma is a promising alternative to in-feed antimicrobials for piglets, particularly during the early stages of the post-weaning phase. Additionally, there is enough evidence to support that commercial spray dried porcine plasma is a safe product for pigs.
In this study, we investigated intestinal barrier function during inflammation as well as the effects of dietary supplementation with porcine spray-dried animal plasma (SDAP) proteins and porcine immunoglobulin concentrate (IC). Wistar Lewis rats were fed from d 21 (weaning) until d 34 or 35 either a control diet or a diet containing SDAP or IC. On d 30 and d 33, rats received an intraperitoneal dose of Staphylococcus aureus enterotoxin B (SEB; 0.5 mg/kg body wt; groups SEB, SEB-SDAP, and SEB-IC). SEB reduced the potential difference across the jejunum by 60%, the short-circuit current by 70%, and Na-K-ATPase activity in intestinal mucosa (all P < 0.05). The fluxes of dextran flux (4 kDa) and horseradish peroxidase (HRP, 40 kDa) across the intestinal wall also increased in SEB-treated rats (P < 0.01, P = 0.068, respectively). SEB also increased HRP flux across the paracellular space (P < 0.05). Moreover, SEB-treated rats had a reduced expression of tight junction proteins, such as ZO-1 (10% reduction; P < 0.05) and β-catenin (20% reduction; P < 0.05). Dietary supplementation with SDAP or IC prevented dextran (P < 0.05) and HRP (P < 0.05) paracellular flux across the intestinal epithelium. SDAP supplementation also prevented SEB effects on Na-K-ATPase activity (P < 0.05). In our model of SEB-induced intestinal inflammation, the increased permeability across the intestinal mucosa was due to the lower expression of tight junction proteins, an effect that can be prevented by both SDAP and IC supplementation.
The aim of this study was to determine the potential modulatory effects of diets supplemented with spray-dried animal plasma (SDAP) or immunoglobulin concentrates (IC) on the immune response of rats challenged with Staphylococcus aureus enterotoxin B (SEB). Lewis rats were fed diets containing 80 g of SDAP/kg diet, 22.7 g of IC/kg diet, or milk proteins (Control diet) from postnatal d 21 (weaning) for 14 d. On d 30 and 33, rats were given SEB (0.5 mg/kg body weight; i.p.). Organized gut-associated lymphoid tissue (GALT) populations, intestinal secretion, mucosal and serum immunoglobulin concentrations, and neutrophil infiltration were studied. On d 35, blood was collected under anesthesia and samples of intestinal mucosa, Peyer's patches, mesenteric lymph nodes (MLN), and spleen were taken. SEB increased the water content of feces, which was prevented by diets containing either SDAP (P < 0.002) or IC (P < 0.001), indicating that plasma protein–supplemented diets can reverse the SEB-induced secretory response. In Peyer's patches, the diet containing SDAP partially prevented the SEB-induced increase in T lymphocytes (P < 0.1) and reduced the percentage of activated T helper cells (P < 0.05). In MLN, activated T lymphocytes were increased by SEB but they were not affected by diet. No effects of SEB or dietary supplementation on mucosal IgA and serum IgA and IgG were observed. The effects of SDAP supplementation on the lymphocyte populations of GALT in rats challenged with SEB support the view that SDAP can modulate the immune response and suggest that plasma protein supplementation can prevent GALT from possible activation by luminal bacterial superantigens.
We examined whether oral plasma protein supplements affect the innate immune response in a model of acute lung inflammation. Mice were fed diets supplemented with 8 % spray-dried plasma (SDP) or 2 % plasma Ig concentrate (IC) from day 19 (weaning) until day 34. The mice were challenged with intranasal lipopolysaccharide (LPS) at day 33 (and killed 24 h later for cytokine and leucocyte analyses) or at day 34 (and killed 6 h later for cytokine determinations). In bronchoalveolar lavage fluid (BALF), LPS increased the number of leucocytes by twenty-sevenfold, an effect that was partly prevented by both SDP and IC, and by twentyfold the percentage of activated monocytes, which was partly prevented by SDP. In the lung tissue, LPS increased the infiltrated leucocytes, and this effect was prevented in part by SDP. In unchallenged mice, both SDP and IC diets reduced the percentage of resident neutrophils and monocytes (P < 0·05). In the blood, both SDP and IC completely prevented LPS-dependent monocyte activation (CD14+; P < 0·05). LPS dramatically increased the concentration of cytokines (TNF-α, IL-1α, IL-6, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor) and chemokines (CXCL1, CCL2, CCL3 and CCL4) in BALF. The acute response of cytokine production was reduced by 20–80 % by both SDP and IC. For chemokines, plasma supplements had no effect on LPS-induced CXCL1 expression but significantly reduced CCL2, CCL3 and CCL4 production (P < 0·05). The results support the view that dietary plasma proteins can be used to attenuate endotoxin-associated lung inflammation.