Redox balance and immunity of piglets pre- and post-E. coli challenge after treatment with hemp or fish oil, and vitamin E.

This study investigated the influence of polyunsaturated fatty acid composition and vitamin E supplementation on oxidative status and immune responses in weanling piglets pre- and post-E. coli challenge. Suckling piglets (n = 24) were randomly selected from two litters for an oral supplementation (1 mL/day) with fish oil or hemp oil and vitamin E supplementation (60 mg natural vitamin E/mL oil) from day 10 to 28 of age. At day 29 and 30 of age, each piglet was orally inoculated with 6.7 × 108 and 3.96 × 108 CFU of F4 and F18 E. coli, respectively. Blood was sampled from all piglets on day 28 before E. coli challenge and on day 35 of age to investigate immunological and oxidative stress markers in plasma. One week after weaning and exposure to E. coli, a general reduction in the α-tocopherol concentration and activity of GPX1 was obtained. Vitamin E supplementation lowered the extent of lipid peroxidation and improved the antioxidative status and immune responses after E. coli challenge. Hemp oil had the greatest effect on antioxidant enzyme activity. Provision of hemp oil and vitamin E to suckling piglets may reduce the incidence of post-weaning diarrhea.

Impact of liquid diet supplementation while suckling and weaning age on nutritional status, intestinal health, and immunity of piglets pre- and post-weaning.

New strategies are needed to enhance piglets' robustness and proper functional development and maturation of piglets' intestine before weaning, to reduce the number of antibiotic treatments of diarrheic disorders in newly weaned piglets. It was hypothesized that a liquid nutritional supplement during the suckling period, and/or an increased weaning age, would beneficially impact piglets' gut health and enhance piglets' nutritional status before weaning. Further, it was hypothesized that a high intake of colostrum during the first 24 h after birth would be more advantageous for piglets' growth and robustness when compared to a low colostrum intake (CI). A 2 × 2 factorial design with two nutritional strategies (± supplementation with milk/feed, i.e., milk provided from day 2 shifted to wet feed at day 12 of age) and two weaning ages (days 24 vs. 35) was used. In total, 460 piglets from 24 sows were used for estimation of the individual CI after birth. Provision of the nutritional supplement and the increased weaning age improved the nutritional status of piglets' post-weaning assessed by their blood plasma concentration of albumin (P = 0.04), triglycerides (P = 0.004), and nonesterified fatty acids (P = 0.02). Piglets with high CI demonstrated improved nutritional status when compared to low CI (P = 0.04). Villous height and crypt depth were greater in piglets weaned at day 35 of age in contrast to day 24 of age (P < 0.001) irrespective of the nutritional intervention (P = 0.82). The concentration of branched-chain fatty acids in piglets' digesta was reduced in groups provided the nutritional supplement (P = 0.01), while total short-chain fatty acids were elevated at weaning in large intestinal digesta of piglets weaned at day 35 of age compared to piglets weaned at day 24 of age (P = 0.05). The weaning age in combination with the nutritional supplement had pronounced beneficial effect on gene expression of all investigated genes: interleukin-6, interleukin-10, nuclear factor kappa-beta, occludine, prostaglandin-endoperoxide synthase-2, tumor necrosis factor-alpha, and zonula occludens-1 (ZO-1) (P = 0.04). In conclusion, nutritional supplementation preweaning combined with increased weaning age could be considered as a strategy for improvement of the intestinal health, function, and maturation in piglets pre- and post-weaning, and a high CI enhanced piglets' robustness before weaning.

Antimicrobial resistance, induced by increased usage of antimicrobials, is a threat raising economic and public health concerns. The great amount of antibiotics used in the animal production and especially in the pig industry, where the greatest part of all prescribed antibiotics is used for treatments of diarrhea in newly weaned piglets. Therefore, there is a call for action to reduce antimicrobial treatments of weaned pigs. Piglets' individual characteristics at weaning have a great impact on the gut health of piglets after weaning. Thus, the proper functional development and maturation of the intestine before weaning will prevent the development of diarrhea and by that reduce the number of antimicrobial treatments. This study aimed to investigate the potential beneficial effect of a liquid nutritional supplement during the suckling period, and/or an increased weaning age on piglets' gut health and maturation, as well as advantageousness of high colostrum intake during the first 24 h after birth for piglets' growth and robustness. We found that the nutritional supplementation before weaning combined with increased weaning age could be considered as a strategy for improvement of intestinal health, function, and maturation in piglets before and after weaning, and high individual colostrum intake enhanced piglets' robustness before weaning.

The effect of nutritional interventions in acute radiation-induced diarrhoea in patients with primary pelvic cancer: A systematic review.

Acute radiation-induced diarrhoea (RID) is a well-known side effect of external radiation therapy for pelvic cancer. Acute RID is an unresolved clinical problem in approximately 80% of patients. We investigated the effect of nutritional interventions on acute RID in patients with pelvic cancer treated with curative radiotherapy. A search was conducted using PubMed, Embase.com, CINAHL, and Cochrane Library, from 1 January 2005 until 10 October 2022. We included randomised controlled trials or prospective observational studies. Eleven of the 21 identified studies had low quality of evidence, mainly because of low patient numbers distributed among several cancer diagnoses, and non-systematic assessment of acute RID. Interventions included probiotics (n = 6), prebiotics (n = 6), glutamine (n = 4), and others (n = 5). Five studies, of which two provided high quality evidence, showed that probiotics improved acute RID. Future well-designed studies investigating the effects of probiotics on acute RID are warranted. PROSPERO ID: CRD42020209499).

Dietary proanthocyanidins promote localized antioxidant responses in porcine pulmonary and gastrointestinal tissues during Ascaris suum-induced type 2 inflammation.

Proanthocyanidins (PAC) are dietary polyphenols with putative anti-inflammatory and immunomodulatory effects. However, whether dietary PAC can regulate type-2 immune function and inflammation at mucosal surfaces remains unclear. Here, we investigated if diets supplemented with purified PAC modulated pulmonary and intestinal mucosal immune responses during infection with the helminth parasite Ascaris suum in pigs. A. suum infection induced a type-2 biased immune response in lung and intestinal tissues, characterized by pulmonary granulocytosis, increased Th2/Th1 T cell ratios in tracheal-bronchial lymph nodes, intestinal eosinophilia, and modulation of genes involved in mucosal barrier function and immunity. Whilst PAC had only minor effects on pulmonary immune responses, RNA-sequencing of intestinal tissues revealed that dietary PAC significantly enhanced transcriptional responses related to immune function and antioxidant responses in the gut of both naïve and A. suum-infected animals. A. suum infection and dietary PAC induced distinct changes in gut microbiota composition, primarily in the jejunum and colon, respectively. Notably, PAC consumption substantially increased the abundance of Limosilactobacillus reuteri. In vitro experiments with porcine macrophages and intestinal epithelial cells supported a role for both PAC polymers and PAC-derived microbial metabolites in regulating oxidative stress responses in host tissues. Thus, dietary PAC may have distinct beneficial effects on intestinal health during infection with mucosal pathogens, while having a limited activity to modulate naturally-induced type-2 pulmonary inflammation. Our results shed further light on the mechanisms underlying the health-promoting properties of PAC-rich foods, and may aid in the design of novel dietary supplements to regulate mucosal inflammatory responses in the gastrointestinal tract.

Depletion and enrichment of phytosterols in soybean oil lipid emulsions directly associate with serum markers of cholestasis in preterm parenteral nutrition-fed pigs.

BACKGROUND: Clinical reports show a positive correlation between phytosterol concentrations and severity of cholestatic liver disease markers in infants during long-term administration of parenteral lipid emulsions. Establishing a causal link between phytosterols and cholestasis has been complicated by confounding factors of lipid emulsion load, fatty acid composition, and vitamin E in many of these studies. The goal of this study is to determine whether altering the phytosterol concentration within a common soybean oil-based emulsion will alter the onset and severity of cholestasis in parenterally fed preterm piglets. METHODS: Preterm piglets were administered, for 21 days, either enteral nutrition (ENT) or parenteral nutrition (PN) prepared from a soybean oil-based emulsion containing either 24.0% (depleted [DEP]), 100% (Intralipid; normal phytosterol [NP] concentration), or 144% (enriched [ENR]) total phytosterol concentration. RESULTS: At the end of the study, plasma and liver phytosterol concentrations were highest in the ENR group, followed by NP and then DEP and ENT. Serum direct bilirubin, serum bile acids, and γ-glutamyltransferase were higher in the ENR and NP groups compared with either DEP or ENT groups. All PN lipid groups showed evidence of mild hepatic steatosis but no change in hepatic expression of proinflammatory cytokines or Farnesoid X receptor target genes. CONCLUSION: The increase in serum direct bilirubin was lower in the DEP group vs the lipid emulsions with normal or ENR phytosterols. Our results provide additional evidence that phytosterols are linked to an increase in serum markers of cholestasis in preterm PN-fed pigs.

Etiology of Colitis-Complex Diarrhea in Growing Pigs: A Review.

Colitis-complex diarrhea (CCD) in pigs can be defined as a type of diarrhea, which is associated with colonic inflammation and disrupted colonic gut barrier functionality in growing pigs (4-16 weeks post-weaning). It is a challenge for the pig industry as it is associated with the high use of antibiotics, reduced animal welfare, and depressed growth rate. The exact etiology of CCD is still unclear; however, pathogens including Brachyspira (B.) hyodysenteriae, B. pilosicoli, and swine whipworms such as Trichuris (T.) suis have been involved in specific colitis (SC). In the absence of specific pathogens, dietary factors, such as high levels of protein, pelleted feedstuffs, and lack of sufficient antioxidants, can result in non-specific colitis (NSC). On the other hand, supplement of polyunsaturated fatty acids (PUFA) and polyphenols, sufficient supply of essential amino acids (e.g., threonine, cysteine, and proline), short-chain fatty acids (SCFA; especially butyrate), and resistant starch have shown to confer preventing/ameliorating effects on CCD. Different putative biomarkers associated with CCD have been presented. It is anticipated that a comprehensive picture of the possible causes of CCD and potential dietary interventions could cast light on the direction of future studies aimed at developing preventive and curative strategies against CCD in growing pigs.

Antibacterial and immunomodulatory effects of Pheromonicin-NM on Escherichia coli-challenged bovine mammary epithelial cells.

Mastitis affects cows in all regions of the world and Escherichia coli (E. coli) is by far the most common reason of mastitis. Now antibiotic therapy is still the preferred approach of treating mastitis. However, antibiotic usage is easy to lead to antibiotic resistance. There is an urgent need for developing efficacious alternative antimicrobials. Pheromonicin-NM (PMC-NM) is a new engineered bactericidal peptide consisting of colicin Ia and an anti-porin A antibody mimetic. It can lead to the dissipation of cellular energy and therefore kill the bacteria rapidly. The aim of the present study was to investigate the comparative effects of PMC-NM and antibiotic ceftiofur on antibacterial and innate immune responses of bovine mammary epithelial cells (BMEC) to E. coli infection. We found that E. coli growth was inhibited by PMC-NM from 0.5 h after treatment and was completely inhibited at 3 h, indicating a rapid antibacterial activity for PMC-NM. The mRNA expression of TLR2, IL-1ß, IL-8, lactoferrin, LAP, TAP and DEFB1 was increased by PMC-NM treatment at 2 h after E. coli infection, suggesting the enhanced inflammatory responses induced by PMC-NM contribute to pathogens clearance at early phase. By contrast, in E. coli-infected BMECs, ceftiofur treatment upregulated TLR2 and NOD2 levels at 12 h, and extremely elevated transcription levels of TNF-α, IL-1ß, IL-8, lactoferrin, LAP, TAP, BNBD5, DEFB1 at 6 h. The excessive expression of these genes at later phase can induce uncontrolled inflammatory responses and finally cause damage. Taken together, PMC-NM might be used as an ideal antibacterial agent against E. coli mastitis.

Rifampicin, not vitamin E, suppresses parenteral nutrition-associated liver disease development through the pregnane X receptor pathway in piglets.

Infants receiving long-term parenteral nutrition (PN) develop PN-associated liver disease (PNALD). We previously (Ng K et al. JPEN J Parenter Enteral Nutr 40: 656-671, 2016. doi:10.1177/0148607114567900.) showed that PN containing soy-based lipid supplemented with vitamin E (α-tocopherol) prevents the development of PNALD. We hypothesize that this occurs via vitamin E activation of pregnane X receptor (PXR)-mediated pathways involved in bile acid metabolism. Neonatal piglets received PN for 14 days containing Intralipid (IL; soy-based lipid emulsion), IL supplemented with 12.6 mg·kg-1·day-1 vitamin E (VITE), or IL with 10 mg·kg-1·day-1 Rifadin IV (RIF), a PXR agonist. Pigs treated with IL and VITE, but not RIF, developed cholestasis and hyperbilirubinemia, markers of liver disease. The hepatic PXR target genes CYP3A29 and UGT1A6 increased during RIF treatment. RIF also modestly increased metabolism of chenodeoxycholic acid to the more hydrophilic bile acid hyocholic acid. Serum fibroblast growth factor (FGF)-19, a key regulator in suppressing hepatic bile acid synthesis, significantly increased in the RIF group. We conclude rifampicin modified markers of PNALD development by increased metabolism of bile acids and potentially suppressed bile acid synthesis. Vitamin E was ineffective at high lipid doses in preventing PNALD.NEW & NOTEWORTHY Intravenous vitamin E and rifampicin were administered to neonatal piglets receiving parenteral nutrition to determine their efficacy in reducing the progression of parenteral nutrition-associated liver disease (PNALD). Rifampicin increased serum FGF-19 concentrations and synthesis of the bile acid hyocholic acid which led to a reduction of PNALD parameters at 2 wk of administration. This result has potential clinical implications for the use of rifampicin as a safe and inexpensive treatment for short-term development of PNALD.

Influence of silver nanoparticles on growth and health of broiler chickens after infection with Campylobacter jejuni.

BACKGROUND: Silver nanoparticles (AgNP) have gained much attention in recent years due to their biomedical applications, especially as antimicrobial agents. AgNP may be used in poultry production as an alternative to the use of antibiotic growth promoter. However, little is known about the impact of oral administration of AgNP on the gut microbiota and the immune system. The aim of the present study was to investigate the effects of AgNP on growth, hematological and immunological profile as well as intestinal microbial composition in broilers challenged with Campylobacter jejuni (C. jejuni). RESULTS: AgNP did not affect the intestinal microbial profile of birds. The body weight gain and the relative weights of bursa and spleen were reduced when supplemented with AgNP. There was no difference with respect to packed cell volume. However, the plasma concentrations of IgG and IgM were lower in birds receiving AgNP compared to the non-supplemented control group. The expression of TNF-α and NF-kB at mRNA level was significantly higher in birds receiving AgNP. CONCLUSIONS: The application of AgNP via the drinking water in the concentration of 50 ppm reduced broiler growth, impaired immune functions and had no antibacterial effect on different intestinal bacterial groups, which may limit the applicability of AgNP against C. jejuni in broiler chickens.

Effects of vitamin D and its metabolites on cell viability and Staphylococcus aureus invasion into bovine mammary epithelial cells.

Vitamin D has been found have various biological effects that may be potent in preventing bovine mastitis. Two forms of vitamin D, vitamin D2 (D2) and vitamin D3 (D3), can be hydroxylated to functional metabolites in cattle. The objectives of the present study were to investigate the potential of vitamin D compounds for controlling bovine mastitis using in vitro cell models, and to compare the differences between D2 and D3 compounds. Results showed that D2 compounds have comparable effects to their D3 analogues on inhibiting MAC-T cell viability in vitro. S. aureus growth was inhibited by high concentrations of D2, D3, 25(OH)D2 and 25(OH)D3. 25(OH)D2 and 25(OH)D3 induced CYP24A1 expression but reduced VDR mRNA expression, whereas the expression of CYP27B1, occludin, and E-cadherin did not change. Additionally, the induction of CYP24A1 expression by 25(OH)D3 was higher than that of 25(OH)D2, which may contribute to their differences in inhibiting cell viability. S. aureus invaded into MAC-T cells and universally inhibited gene expressions. Pre-treat MAC-T cells with 25(OH)D2 reduced S. aureus adhesion while pre-treatment with 25(OH)D3 inhibited S. aureus invasion, but neither of the compounds attenuated the S. aureus-induced gene expression reduction. In conclusion, the present study shows that D2 compounds have comparable effects on inhibiting cell viability and S. aureus invasion to their D3 analogues in vitro, suggesting that D2 and its metabolites have potential in controlling bovine mastitis.

Pasteurization Procedures for Donor Human Milk Affect Body Growth, Intestinal Structure, and Resistance against Bacterial Infections in Preterm Pigs.

Background: Holder pasteurization (HP) destroys multiple bioactive factors in donor human milk (DM), and UV-C irradiation (UVC) is potentially a gentler method for pasteurizing DM for preterm infants.Objective: We investigated whether UVC-treated DM improves gut maturation and resistance toward bacterial infections relative to HP-treated DM.Methods: Bacteria, selected bioactive components, and markers of antioxidant capacity were measured in unpasteurized donor milk (UP), HP-treated milk, and UVC-treated milk (all from the same DM pool). Fifty-seven cesarean-delivered preterm pigs (91% gestation; ratio of males to females, 30:27) received decreasing volumes of parental nutrition (average 69 mL · kg-1 · d-1) and increasing volumes of the 3 DM diets (n = 19 each, average 89 mL · kg-1 · d-1) for 8-9 d. Body growth, gut structure and function, and systemic bacterial infection were evaluated.Results: A high bacterial load in the UP (6×105 colony forming units/mL) was eliminated similarly by HP and UVC treatments. Relative to HP-treated milk, both UVC-treated milk and UP showed greater activities of lipase and alkaline phosphatase and concentrations of lactoferrin, secretory immunoglobulin A, xanthine dehydrogenase, and some antioxidant markers (all P < 0.05). The pigs fed UVC-treated milk and pigs fed UP showed higher relative weight gain than pigs fed HP-treated milk (5.4% and 3.5%), and fewer pigs fed UVC-treated milk had positive bacterial cultures in the bone marrow (28%) than pigs fed HP-treated milk (68%) (P < 0.05). Intestinal health was also improved in pigs fed UVC-treated milk compared with those fed HP-treated milk as indicated by a higher plasma citrulline concentration (36%) and villus height (38%) (P < 0.05) and a tendency for higher aminopeptidase N (48%) and claudin-4 (26%) concentrations in the distal intestine (P < 0.08). The gut microbiota composition was similar among groups except for greater proportions of Enterococcus in pigs fed UVC-treated milk than in pigs fed UP and those fed HP-treated milk in both cecum contents (20% and 10%) and distal intestinal mucosa (24% and 20%) (all P < 0.05).Conclusions: UVC is better than HP treatment in preserving bioactive factors in DM. UVC-treated milk may induce better weight gain, intestinal health, and resistance against bacterial infections as shown in preterm pigs as a model for DM-fed preterm infants.

Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs.

It is unclear when and how to start enteral feeding for preterm infants when mother's milk is not available. We hypothesized that early and slow advancement with either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models for preterm infants. Pigs were given either total parenteral nutrition (TPN, n = 14) or slowly advancing volumes (16-64 ml·kg(-1)·day(-1)) of preterm infant formula (IF, n = 15) or bovine colostrum (BC, n = 13), both given as adjunct to parenteral nutrition. On day 5, both enteral diets increased intestinal mass (27 ± 1 vs. 22 ± 1 g/kg) and glucagon-like peptide 2 release, relative to TPN (P < 0.05). The incidence of mild NEC lesions was higher in IF than BC and TPN pigs (60 vs. 0 and 15%, respectively, P < 0.05). Only the IF pigs showed reduced gastric emptying and gastric inhibitory polypeptide release, and increased tissue proinflammatory cytokine levels (IL-1ß and IL-8, P < 0.05) and expression of immune-related genes (AOAH, LBP, CXCL10, TLR2), relative to TPN. The IF pigs also showed reduced intestinal villus-to-crypt ratio, lactose digestion, and some plasma amino acids (Arg, Cit, Gln, Tyr, Val), and higher intestinal permeability, compared with BC pigs (all P < 0.05). Colonic microbiota analyses showed limited differences among groups. Early feeding with formula induces intestinal dysfunction whereas bovine colostrum supports gut maturation when mother's milk is absent during the first week after preterm birth. A diet-dependent feeding guideline may be required for newborn preterm infants.

Effect of maternal intake of organically or conventionally produced feed on oral tolerance development in offspring rats.

The aim of this study was to investigate the effect of maternal consumption of organically or conventionally produced feed on immunological biomarkers and their offsprings' response to a novel dietary antigen. First-generation rats were fed plant-based diets from two different cultivation systems (organic or conventional) or a chow. Second-generation rats were exposed to ovalbumin (OVA) via their mother's milk and subsequently challenged with OVA after weaning onto the chow diet. In the chow diet group feeding the dams OVA resulted in suppression of the pups' anti-OVA antibody response to the OVA challenge (total OVA-specific IgG was 197 for the OVA-treated chow diet group and 823 for the control chow diet group (arbitrary ELISA units)). In contrast, OVA exposure of the dams from the plant-based dietary groups did not result in a similar suppression. Cultivation system had no effect on the immunological biomarkers, except for a higher spleen prostaglandin E2 (PGE2) concentration in pups originating from dams fed the conventional plant-based diet (223 ng/L) than from those fed the organic plant-based diet (189 ng/L).

The effect of dietary fatty acids on post-operative inflammatory response in a porcine model.

The potential anti-inflammatory effects of dietary fish oil (FO) have been studied in numerous clinical trials. However, variation in lifestyle and morbidity among patients can be difficult to control. In the present study, the impact of a 3-week dietary pre-treatment with 10% (w/w) FO (n 28), sunflower oil (SO, n 28), or animal fat (AF, n 28) was evaluated with respect to post-operative responses in inflammatory markers in a porcine model on aortic vascular prosthetic graft infection. In the early post-operative period (0 < day ≤ 3), FO suppressed whole blood IL-8 and tumor necrosis factor-α responsiveness to LPS stimulation, decreased peripheral leukocyte IL-8 mRNA abundance, reinforced an increase in total leukocyte count, and counteracted a decrease in mononuclear leukocyte count compared with SO. In the late post-operative period (3 < day ≤ 14), FO increased total leukocyte count and showed higher maximum CRP and haptoglobin concentrations compared with SO. Compared with AF, FO decreased peripheral leukocyte IL-8 mRNA abundance in the early post-operative period, and increased total leukocyte count and maximum CRP concentration in the late post-operative period. In conclusion, the post-operative response in a number of inflammatory markers was affected by FO, and this was most apparent compared with SO.

n-6 and n-3 fatty acids ratio and vitamin E in porcine maternal diet influence the antioxidant status and immune cell eicosanoid response in the progeny.

Five groups of lactating sows were fed diets containing 8% of either added rapeseed oil, fish oil or sunflower oil and 60 mg vitamin E/kg feed, or the diets with sunflower oil and fish oil, respectively, supplemented with 500 mg vitamin E/kg. Supplementation of vitamin E to the sows increased the concentration of alpha-tocopherol of the muscle, and addition of sunflower oil decreased the activity of glutathione peroxidase in liver cytosol compared to fish oil and rapeseed oil. The composition of fatty acids of alveolar macrophages (AM) of piglets was influenced by the dietary fat sources provided the sows, i.e., the ratio of n-6:n-3 fatty acids was highest in AM of piglets suckling sows of the sunflower oil treatments, and lowest in AM of piglets suckling sows fed fish oil with the rapeseed oil treatment in between. The ex vivo synthesis of prostaglandin E(2) and thromboxane B(2) in AM of piglets suckling sows fed sunflower oil was elevated compared to piglets suckling sows fed fish oil. Vitamin E supplementation to sows enhanced the synthesis of these eicosanoids, and also the concentration of alpha-tocopherol in the AM of the piglets.