Javier Polo

The biological stress of early weaned piglets

Pigs experience biological stress such as physiological, environmental, and social challenges when weaned from the sow. The process of weaning is one of the most stressful events in the pig’s life that can contribute to intestinal and immune system dysfunctions that result in reduced pig health, growth, and feed intake, particularly during the first week after weaning. Technological improvements in housing, nutrition, health, and management have been used to minimize some of the adverse effects of weaning stress, but a greater understanding of the biological impact of stress is needed to improve strategies to overcome weaning stress. The focus of this review paper is to briefly describe how the biological stress associated with weaning impacts intestinal morphology, structure, physiology, and intestinal immune responses that can impact subsequent production efficiencies such as growth, intake, morbidity, and mortality.

Spray-Dried Porcine Plasma Influences Intestinal Barrier Function, Inflammation, and Diarrhea in Weaned Pigs

The objective of this study was to evaluate the effects of dietary inclusion levels of spray-dried porcine plasma (SDPP) on postweaning (PW) intestinal barrier function, mucosal inflammation, and clinical indices of gut health in pigs. Ex vivo Ussing chamber studies were conducted to measure Ileal and colonic barrier function in terms of transepithelial electrical resistance and paracellular flux of (3)H-mannitol and (14)C-inulin. Intestinal inflammation was assessed by histological analysis and mucosal levels of proinflammatory cytokines. Dietary inclusion of 2.5 and 5% SDPP reduced colonic paracellular permeability of (14)C-inulin compared with controls (0% SDPP) on d 7 PW. Both 2.5 and 5% dietary SDPP reduced ileal (3)H-mannitol and (14)C-inulin permeability on d 14 PW. The 5% SDPP diet reduced colonic short-circuit current, an index of net electrogenic ion transport, and fecal scores when measured on d 7 and 14 PW compared with the control and 2.5% SDPP groups (P < 0.05). Histological analysis revealed fewer lamina propria cells in ileum and colon from pigs fed diets containing 2.5 and 5% SDPP on d 7 and 14 PW. Levels of the proinflammatory cytokine TNFα were reduced in the colon but not ileum from pigs fed the 5% SDPP on d 7 and 14 PW compared with controls (P < 0.05). IFNγ levels were lower than in controls in both of the SDPP-fed groups in the ileum and colon on d 7 but not on d 14 PW. Overall, this study demonstrated that dietary inclusion of SDPP had beneficial effects on intestinal barrier function, inflammation, and diarrhea in weaned pigs.

Dietary Plasma Protein Supplements Prevent the Release of Mucosal Proinflammatory Mediators in Intestinal Inflammation in Rats

Spray-dried plasma (SDP) is a complex mixture of active proteins that modulates the immune response of gut-associated lymphoid tissue. We examined whether SDP and Ig concentrate (IC) supplementation could modulate cytokine expression and inflammatory mediators in rats challenged with Staphylococcus aureus enterotoxin B (SEB). Wistar-Lewis rats were fed diets supplemented with SDP (8% wt:wt), IC (1.5% wt:wt), or milk proteins (control diet) from weaning (d 21) to d 34 after birth. On d 32 and 35, the rats were given SEB (0.5 mg/kg; intraperitoneal). Six hours after the second SEB dose, jejunal mucosa and Peyers patches (PP) from the small intestine were collected. The cytokines interferon-gamma (IFNgamma), tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-10, transforming growth factor-beta (TGFbeta), and leukotrienne B(4) (LTB(4)) were analyzed using commercial kits. SEB increased the release of proinflammatory mediators (IFNgamma, TNFalpha, IL-6, and LTB(4)) in PP (P < 0.05) and in the mucosa (P < 0.05). In both tissues, SDP prevented the increase in IFNgamma, IL-6, and LTB(4) induced by SEB (P < 0.05). IC reduced the expression of TNFalpha and LTB(4) in PP and mucosa (P < 0.05). SDP supplementation increased IL-10 and mature TGFbeta concentrations in intestinal mucosa from both inflamed and noninflamed rats. Both SDP and IC increased the mature:total TGFbeta ratio (all P < 0.05). Both supplements were effective at preventing the SEB-induced increase in proinflammatory:antiinflammatory cytokine ratios in PP and mucosa and in serum. The preventive effects of plasma supplements on intestinal inflammation involve modulation of intestinal cytokines, characterized by an increased expression of antiinflammatory cytokines.

Lack of transmission of porcine circovirus type 2 to weanling pigs by feeding them spray-dried porcine plasma.

An experiment was conducted to determine whether spray-dried porcine plasma containing 2·47 × 105 dna copies of porcine circovirus type 2 (pcv-2) could infect weanling pigs when fed to them. Five specific pathogen-free (spf) weanling pigs were fed ad libitum for 45 days a control diet and six pigs were fed a test diet containing 8 kg sdpp per 100 kg feed. The two groups were housed in separate biosecurity level-3 rooms. None of the pigs in either group developed any clinical signs or became pcv-2 viraemic or seroconverted.

Dietary plasma proteins attenuate the innate immunity response in a mouse model of acute lung injury

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.

Commercial spray-dried porcine plasma does not transmit porcine circovirus type 2 in weaned pigs challenged with porcine reproductive and respiratory syndrome virus

The objective of this study was to evaluate if spray dried porcine plasma (SDPP) containing porcine circovirus type 2 (PCV2) genome supplemented in feed could transmit PCV2 to pigs challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Twenty-three PRRSV-free pigs, non-viraemic for PCV2, were housed in bio-safety level 3 facilities and assigned to four groups in a 2×2 factorial design consisting of PRRSV challenge and a negative control. The diet contained 0 or 8kg SDPP per 100kg of feed. PRRSV challenge groups were inoculated intranasally with 2mL of a suspension containing 10(6) TCID(50)/mL PRRSV. The SDPP used in the study contained 7.56×10(5) PCV2 genome copies per gram. Dietary treatments were fed from 4days prior to PRRSV inoculation until 28days post-inoculation (PI). All challenged pigs developed PRRSV viraemia by day 3PI and PRRSV antibodies were detected in sera by day 14PI, with no difference between diet treatments. Neither PRRSV viraemia nor seroconversion was observed in non-challenged pigs. PCV2 was not detected in the serum of any pigs throughout the experimental period. SDPP containing the PCV2 genome supplemented in feed did not result in PCV2 transmission to either healthy or PRRSV-infected pigs under these experimental conditions.

Early Life Dietary Spray Dried Plasma Influences Immunological and Intestinal Injury Responses to Later Life Salmonella Typhimurium Challenge

Increasing evidence supports the concept that early-life environmental influences, including nutrition and stress, have an impact on long-term health outcomes and disease susceptibility. The objective of the present study was to determine whether dietary spray-dried plasma (SDP), fed during the first 2 weeks post-weaning (PW), influences subsequent immunological and intestinal injury responses to Salmonella typhimurium challenge. A total of thirty-two piglets (age 16-17 d) were weaned onto nursery diets containing 0, 2·5 % SDP (fed for 7 d PW) or 5 % SDP (fed for 14 d PW), and were then fed control diets (without SDP), for the remainder of the experiment. At 34 d PW (age 50 d), pigs were challenged with 3 × 10⁹ colony-forming units of S. typhimurium. A control group (non-challenged) that was fed 0 % SDP in the nursery was included. At 2 d post-challenge, the distal ileum was harvested for the measurement of inflammatory, histological and intestinal physiological parameters. S. typhimurium challenge induced elevated ileal histological scores, myeloperoxidase (MPO), IL-8 and TNF, and increased intestinal permeability (indicated by reduced transepithelial voltage (potential difference) and elevated 4 kDa fluorescein isothiocyanate dextran (FD4) flux rates). Compared with S. typhimurium-challenged controls (0 % SDP), pigs fed the 5 % SDP-14 d diet exhibited reduced ileal histological scores, MPO levels, IL-8 levels and FD4 flux rates. Pigs fed the 5 % SDP-14 d nursery diet exhibited increased levels of plasma and ileal TNF-α in response to the challenge, compared with the other treatments. These results indicate that inclusion of SDP in PW diets can have an influence on subsequent immunological and intestinal injury responses induced by later-life S. typhimurium challenge.

Efficacy of dietary spray dried plasma protein to mitigate the negative effects on performance of pigs fed diets with corn naturally contaminated with multiple mycotoxins

The ability of spray dried plasma protein (SDPP) to reduce the negative effects of multiple mycotoxins from naturally contaminated corn on weaned pig performance and health was investigated (n = 180; 6.84 ± 0.11 kg). For 12 d after weaning, pigs were fed phase 1 nursery diets with either 0% SDPP (PP0) or 6% SDPP (PP6). After 12 d, pigs were fed phase 2 diets for 3 wk. Pigs fed PP0 in phase 1 continued to be fed a phase 2 diet with no SDPP (PP0/PP0) or were fed a diet including corn naturally contaminated with multiple mycotoxins (M), labeled PP0/PP0M. Pigs fed SDPP in phase 1 were fed either a diet with no SDPP (PP6/PP0), a diet with M and no SDPP (PP6/PP0M), a diet with M and 3% SDPP (PP6/PP3M), or a diet with M and 6% SDPP (PP6/PP6M). During phase 1, pigs fed PP6 had increased (P < 0.05) ADG, ADFI, and G:F, whereas immunological parameters were not altered. During phase 2, pigs consuming PP0/PP0M had reduced ADG (P < 0.01) and ADFI (P < 0.05) in contrast to pigs fed PP0/PP0, whereas the performance of pigs fed PP6/PP0M was intermediate to pigs fed PP0/PP0M and PP6/PP0. The ADG and ADFI did not differ for pigs fed PP0/PP0M and PP6/PP0M during phase 2. Performance of pigs fed PP6/PP3M in contrast to pigs fed PP6/PP0M during phase 2 did not differ; however, these pigs had lower (P < 0.05) tumor necrosis factor α and tended (P = 0.094) to have lower DNA damage. During phase 2, ADG and ADFI of pigs fed PP6/PP6M did not differ from pigs fed PP6/PP0M, but G:F tended (P = 0.067) to be increased in pigs fed PP6/PP6M. Over the entire study period, pigs fed PP0/PP0M had reduced (P < 0.05) ADG and tended (P = 0.067) to have reduced ADFI. During this time, pigs fed PP6/PP0M tended to have greater ADG and ADFI (P = 0.093 and P = 0.067, respectively) compared with pigs fed PP0/PP0M. Overall, feeding a diet with SDPP improved growth performance and feed intake of young pigs directly after weaning. Feeding multiple M had a negative impact on growth performance of pigs during this trial. This response was more significant when pigs were not fed SDPP in phase 1. Overall, when combining phase 1 and 2 performance data, daily gain and feed intake tended to be reduced when pigs were not fed 6% SDPP in phase 1. This study indicates that the composition of diets fed immediately after weaning may be important for pigs that subsequently are under a M challenge.

Dietary Plasma Proteins Modulate the Adaptive Immune Response in Mice with Acute Lung Inflammation

We examined the effects of oral plasma protein supplements on the pulmonary adaptive immune response in mice challenged with intranasal LPS. C57BL/6 mice were fed a control diet or a diet supplemented with plasma proteins [spray-dried plasma (SDP) 80 g/kg] or with an Ig concentrate [(IC) 20 g/kg] from postnatal d 19 (weaning) until d 34. Mice were challenged with PBS or LPS from Escherichia coli at d 33 and killed 24 h later for leukocyte analyses or at d 34 and killed 6 h later for cytokine determination. LPS induced the activation of T helper (Th) lymphocytes in lung and blood and this response was reduced by SDP and IC (P < 0.05). In both tissues, LPS increased the Th1 and Th2 subpopulations and this effect was inhibited by the two plasma protein supplements (P < 0.05). The LPS challenge increased the expression of all the cytokines studied (P < 0.01). SDP and IC reduced the expression of IFNγ, IL-5, IL-12p40, IL-12p70, IL-13, and IL-17 in both tissues, whereas they increased the percentage of regulatory Th lymphocytes in lung, even in PBS-treated mice (P < 0.05). LPS reduced the concentration of mature TGFβ1 (P < 0.05) in the lung but did not modify the expression of IL-10. Mice exposed to LPS and supplemented with SDP or IC showed an increased expression of the anti-inflammatory cytokine IL-10 (P < 0.05). Moreover, the two supplements increased the concentration of IL-10 in intestinal mucosa (P < 0.05). Our results show that plasma supplementation reduces the immune response that characterizes the acute lung inflammation syndrome.

Bovine immunoglobulin protein isolates for the nutritional management of enteropathy

The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.