Intraductal Drug Delivery to the Breast: Effect of Particle Size and Formulation on Breast Duct and Lymph Node Retention.

Drug delivery by direct intraductal administration can achieve high local drug concentration in the breast and minimize systemic levels. However, the clinical application of this approach for breast cancer treatment is limited by the rapid clearance of the drug from the ducts. With the goal of developing strategies to prolong drug retention in the breast, this study was focused on understanding the influence of particle size and formulation on breast duct and lymph node retention. Fluorescent-labeled polystyrene (PS) particles ranging in size from 100 to 1000 nm were used to study the influence of particle size. Polylactic acid-co-glycolic acid (PLGA) was used to develop and test formulations for intraductal delivery. Cy 5.5, a near-IR dye, was encapsulated in PLGA microparticles, nanoparticles, and the in situ gel to study the biodistribution in rats using an in vivo imager. PS microparticles (1 µm) showed longer retention in the duct compared to 100 and 500 nm nanoparticles. The ductal retention half-life was 5-fold higher for PS microparticles compared to the nanoparticles. On the other hand, the free dye was cleared from the breast within 6 h. PLGA nanoparticles sustained the release of Cy 5.5 for >4 days. Microparticles and gel showed a much slower release than nanoparticles. PLGA in situ gel and microparticles were retained in the breast for up to 4 days, while the nanoparticles were retained in the breast for 2 days. PLGA nanoparticles and microparticles drained to the axillary lymph node and were retained for up to 24 and 48 h, respectively, while the in situ gel and the free dye did not show any detectable fluorescence in the lymph nodes. Taken together, the results demonstrate the feasibility of prolonged retention in the breast duct and lymph node by optimal formulation design. The findings can serve as a framework to design formulations for localized treatment of breast cancer.

Food Protein Based Core-Shell Nanocarriers for Oral Drug Delivery: Effect of Shell Composition on in Vitro and in Vivo Functional Performance of Zein Nanocarriers.

The study was aimed at systematically investigating the influence of shell composition on the particle size, stability, release, cell uptake, permeability, and in vivo gastrointestinal distribution of food protein based nanocarriers for oral delivery applications. Three different core-shell nanocarriers were prepared using food-grade biopolymers including zein-casein (ZC) nanoparticles, zein-lactoferrin (ZLF), nanoparticles and zein-PEG (ZPEG) micelles. Nile red was used as a model hydrophobic dye for in vitro studies. The nanocarriers had negative, positive, and neutral charge, respectively. All three nanocarriers had a particle size of less than 200 nm and a low polydispersity index. The nanoparticles were stable at gastrointestinal pH (2-9) and ionic strength (10-200 mM). The nanocarriers sustained the release of Nile red in simulated gastric and intestinal fluids. ZC nanoparticles showed the slowest release followed by ZLF nanoparticles and ZPEG micelles. The nanocarriers were taken up by endocytosis in Caco-2 cells. ZPEG micelles showed the highest cell uptake and transepithelial permeability followed by ZLF and ZC nanoparticles. ZPEG micelles also showed P-gp inhibitory activity. All three nanocarriers showed bioadhesive properties. Cy 5.5, a near IR dye, was used to study the in vivo biodistribution of the nanocarriers. The nanocarriers showed longer retention in the rat gastrointestinal tract compared to the free dye. Among the three formulations, ZC nanoparticles was retained the longest in the rat gastrointestinal tract (≥24 h). Overall, the outcomes from this study demonstrate the structure-function relationship of core-shell protein nanocarriers. The findings from this study can be used to develop food protein based oral drug delivery systems with specific functional attributes.

Research note: Nutritive value of cold-pressed flaxseed meal for broiler chicken.

A study was conducted to evaluate standardized ileal digestibility (SID) of amino acids (AA) and N-corrected apparent metabolizable energy (AMEn) values of cold pressed flaxseed meal (CPFM) for broilers. One hundred and twenty broiler chicks were divided into 20 groups of 6 birds/group and fed 2 diets in a completely randomized design (10 groups/diet) from 14 to 21 d of age. The diets were cornstarch-based containing CPFM or conventional soybean meal (SBM; reference feedstuff) as the sole protein source. A N-free diet fed in another study conducted in the same facility and at the same time that the current study was conducted was used to estimate basal endogenous AA losses, and to calculate gross energy retention by difference method. The CPFM had greater neutral detergent fiber and ether extract contents (21.40 vs. 8.18% and 20.4 vs. 2.47% as is, respectively), but lower CP (20.47 vs. 48.28% as is) than SBM. The SID values of all indispensable AA (except for Leu, Phe and Trp) for CPFM were lower (P < 0.05) than those for SBM. The apparent retention of gross energy (65.95 vs. 44.24%) and N (55.53 vs. 9.79%), and AMEn (2,699 vs. 2,491 kcal/kg) for CPFM were lower (P < 0.05) than those for SBM. In conclusion, CPFM can serve as alternative oilseed co-product feedstuff for poultry. However, the CPFM has lower SID of AA and AMEn values than SBM likely due to the greater fiber content in the former than in the latter.

Zinc status and indicators of intestinal health in enterotoxigenic Escherichia coli F18 challenged newly weaned pigs fed diets with different levels of zinc.

This study investigated the impact of an enterotoxigenic Escherichia coli (ETEC) F18 challenge on newly weaned pigs when fed one of three Zn levels (150, 1,400, or 2,500 ppm) on performance, Zn status, ETEC shedding, and diarrhea. The ETEC challenge was hypothesized to have a more pronounced negative impact on pigs fed a diet containing 150 ppm Zn compared to 1,400 or 2,500 ppm Zn for 14 d after weaning. The study included 72 ETEC F18 susceptible pigs weaned at ~28 d of age (d 0 of the study). The pigs were distributed according to initial weight and litter to one of the three dietary Zn levels. Half of the pigs were challenged with ETEC on d 1 and 2. The challenge reduced (P ≤ 0.03) feed intake and average daily gain (ADG) during d 3 to 5. Challenged pigs fed 150 ppm Zn had lower (P = 0.01) ADG during d 5 to 7 compared to those fed 1,400 or 2,500 ppm Zn, whereas control pigs' ADG were not affected by dietary Zn content. Challenged pigs fed 150 ppm Zn also showed lower (P < 0.01) fecal dry matter (DM) on d 5 compared to control pigs fed 150 ppm Zn and challenged pigs fed 1,400 or 2,500 ppm Zn. Challenge increased (P < 0.01) ETEC shedding in all groups, but challenged pigs fed 150 ppm Zn showed higher (P ≤ 0.05) fecal shedding of ETEC and toxins than when fed 1,400 or 2,500 ppm. On d 3, C-reactive protein concentration in plasma was lower (P < 0.03) for pigs fed 1,400 and 2,500 compared to 150 ppm Zn. Plasma haptoglobin and pig major acute phase protein were unaffected by dietary Zn content. On d 0, the serum Zn concentration was 586 ±â€…36.6 µg/L, which pigs fed 150 ppm Zn maintained throughout the study. The serum Zn concentration increased (P ≤ 0.07) in pigs fed 1,400 or 2,500 ppm Zn. The challenge decreased (P < 0.01) the serum Zn concentration in pigs fed 2,500 ppm Zn. On d 5 and 7, serum Zn concentration was similar for challenged pigs fed 1,400 and 2,500 ppm Zn, while control pigs fed 2,500 ppm Zn had higher (P < 0.01) serum Zn concentration than 1,400 ppm Zn. On d 7, serum Zn concentration tended (P = 0.08) to be lower for pigs with diarrhea (fecal DM ≤ 18%). In summary, these results indicate that newly weaned pigs fed 150 ppm Zn are more susceptible to ETEC F18 colonization and its adverse consequences such as diarrhea and reduced growth, even though challenge did not increase acute phase proteins.

At weaning, the immune system of pigs is not fully developed, leaving them more susceptible to infections such as enterotoxigenic Escherichia coli (ETEC) F18. This study investigated the effect of dietary zinc content on newly weaned pigs infected with ETEC in terms of performance, serum zinc status, diarrhea, E. coli shedding, and systemic inflammation markers. Challenged pigs had reduced growth the first 3 d after the challenge when fed 150 ppm dietary Zn compared to non-challenged pigs. Moreover, the challenge increased E. coli fecal shedding and resulted in more liquid feces, and a greater risk of diarrhea in pigs fed 150 ppm zinc compared to 1,400 and 2,500 ppm zinc. The challenge was not able to induce a response in the acute phase proteins. The serum zinc concentration was lowest when feeding 150 ppm, and the ETEC challenge caused a reduction in the serum Zn concentration only when feeding 2,500 ppm zinc. These findings suggest that newly weaned pigs fed 150 ppm zinc are less capable of withstanding an ETEC challenge based on impaired growth performance and increased diarrhea and E. coli shedding.

Determination of the optimal dietary zinc content for pigs between 10 and 30 kg body weight.

The Zn requirement of pigs immediately after weaning is more investigated compared to the Zn requirement in the growth period between 10 and 30 kg. Unabsorbed and excessive dietary Zn is excreted mainly through feces, and spreading pig slurry to fields can cause environmental issues because high levels of Zn can impair plant growth and contribute to the development of antimicrobial resistance genes in microorganisms. Therefore, more precise knowledge of Zn requirements and dietary Zn recommendations is important. The present study investigated the optimal dietary Zn content for 10- to 30-kg pigs. The study used 150 pigs weaned at 28 d of age (day 0) and supplied with 1,474 mg dietary Zn/kg the first 2 wk post-weaning. After 2 wk, pigs were randomly distributed according to body weight (BW; 10.1 ±â€…0.3 kg) and sex, to individually housing, and fed a diet supplemented with either 0, 30, 60, 120, or 240 mg Zn/kg (from ZnO), resulting in total dietary Zn contents of 80, 92, 117, 189, and 318 mg/kg until week 6 post-weaning. BW, feed intake, and fecal scores were recorded, and samples of blood (weeks 2, 3, 5, and 6) and tissues (week 6) were collected. The feed intake, growth, feed efficiency, relative weight of the pancreas and liver, Zn concentration in the liver, and pancreatic digestive enzyme activity were unaffected by dietary Zn content (P > 0.12). The serum Zn level decreased (P < 0.01) by up to 24% from weeks 2 to 3. The serum Zn concentrations in weeks 5 and 6 were similar to in week 2 when 117, 189, and 318 mg Zn/kg were provided, while with 80 and 92 mg Zn/kg the serum Zn concentration was lower (P < 0.01) than in week 2. The serum Zn concentration reached a plateau in weeks 5 and 6, and breakpoints were calculated at 126 ±â€…17 and 102 ±â€…6 mg Zn/kg, respectively. Bone Zn status was greater (P < 0.01) with 189 than 80 mg Zn/kg and a breakpoint was calculated at 137 ±â€…19 mg Zn/kg. According to performance, the Zn requirement for 10- to 30-kg pigs can be fulfilled with 80 mg total Zn/kg, but based on serum and bone Zn status, the optimal total dietary Zn content is 102 to 137 mg/kg. The latter corresponds to a daily Zn intake (requirement) of 103 to 138 mg when calculated from the average feed intake during weeks 3 to 6 (1,005 g/d). Importantly, the presented results are obtained in pigs supplied with 1,474 mg Zn/kg from ZnO the first 2 wk post-weaning and a high level of phytase (1,000 phytase units) in the diet throughout the experiment.

It is important to ensure that the dietary zinc (Zn) content fulfills the Zn requirement of pigs. The unabsorbed proportion of dietary Zn is excreted mainly through feces and supplying pigs with more Zn than they need increases the excretion, which may be an environmental issue. This study investigated the optimal dietary Zn content in 10- to 30-kg pigs. From weaning until 10 kg (the first 2 wk post-weaning) pigs were fed a diet containing 1,474 mg Zn/kg. From the third to the sixth week post-weaning (10- to 30-kg) pigs were fed a basal diet supplemented with either 0, 30, 60, 120, or 240 mg Zn/kg from zinc oxide. Analysis of the five experimental diets showed total Zn contents of 80, 92, 117, 189, and 318 mg/kg. The feed intake, weight gain, and feed efficiency were unaffected by dietary Zn content. The Zn concentration in serum (blood) at the end of the experiment was lowest with 80 and 92 mg total Zn/kg compared to 117, 189, and 318 mg total Zn/kg, which resulted in similar serum Zn concentration. The Zn content in bone was lower at 80 compared to 189 mg total Zn/kg.

Nutritive value of expeller/cold-pressed canola meal and pre-pressed solvent-extracted carinata meal for broiler chicken.

A study was conducted to evaluate standardized ileal digestibility (SID) of amino acids (AA) and nitrogen-corrected apparent metabolizable energy (AMEn) values of pre-pressed solvent-extracted carinata meal (SE-carinata meal) and expeller/cold-pressed canola meal (ECP-canola meal) for broilers. Two hundred and forty broiler chicks were divided into 40 groups of 6 birds/group and fed 4 diets in a completely randomized design (10 groups/diet) from 14 to 21 d of age. The diets were cornstarch-based containing SE-carinata meal, ECP-canola meal, or pre-pressed solvent-extracted canola meal (SE-canola meal; reference feedstuff) as the sole protein source, and N-free diet. Digestibility of AA and N retention for feedstuffs was determined by the direct method, whereas energy retention of feedstuffs was determined by difference from the N-free diet. On DM basis, SE-canola meal, ECP-canola meal, and SE-carinata meal contained 43, 36, and 50% CP; 2.60, 2.21, and 1.82% Lys; 32, 29, and 27% neutral detergent fiber, and 1.1, 15.3, and 0.88% ether extract, respectively. On DM basis, the AMEn value was lowest (P < 0.05) for SE-carinata meal (1,295 kcal/kg), intermediate (P < 0.05) for SE-canola meal (1,608 kcal/kg), and greatest (P < 0.05) for ECP-canola meal (1,994 kcal/kg). The SID values of indispensable AA for ECP-canola meal were greater (P < 0.05) than those for SE-canola meal or SE-carinata meal. The SID values of all indispensable AA (except Gly, Lys, and Trp) for SE-carinata meal were greater (P < 0.05) than those for SE-canola meal. The SE-canola meal and SE-carinata meal did not differ in SID of Gly and Trp; however, SE-carinata meal had lower (P < 0.05) SID of Lys than SE-canola meal. The results indicate that ECP-canola meal fed in this study could be a good source of AA and energy for broilers. Results also indicate that SE-carinata meal fed in this study could be an attractive AA source for broiler diet, but could benefit from Lys fortification due it its low SID Lys value.

Growth performance, bone mineralization, nutrient digestibility, and fecal microbial composition of multi-enzyme-supplemented low-nutrient diets for growing-finishing pigs.

A study evaluated the effects of adding multi-enzyme mixture to diets deficient in net energy (NE), standardized ileal digestible (SID) amino acids (AA), standardized total tract digestible (STTD) P, and Ca on growth performance, bone mineralization, nutrient digestibility, and fecal microbial composition of grow-finish pigs. A total of 300 pigs (initial body weight [BW] = 29.2 kg) were housed by sex and BW in 45 pens of 7 or 6 pigs and fed 5 diets in a randomized complete block design. Diets were positive control (PC), and negative control 1 (NC1) or negative control 2 (NC2) without or with multi-enzyme mixture. The multi-enzyme mixture supplied at least 1,800, 1,244, 6,600, and 1,000 units of xylanase, ß -glucanase, arabinofuranosidase, and phytase per kilogram of diet, respectively. The PC was adequate in all nutrients. The NC1 diet had lower content NE, SID AA, STTD P, and Ca than PC diet by about 7%, 7%, 32%, and 13%, respectively. The NC2 diet had lower NE, SID AA, STTD P, and Ca than PC diet by 7%, 7%, 50%, and 22%, respectively. The diets were fed in four phases based on BW: Phase 1: 29-45 kg, Phase 2: 45-70 kg, Phase 3: 70-90 kg, and Phase 4: 90-120 kg. Nutrient digestibility, bone mineralization, and fecal microbial composition were determined at the end of Phase 1. Pigs fed PC diet had greater (P < 0.05) overall G:F than those fed NC1 diet or NC2 diet. Multi-enzyme mixture increased (P < 0.05) overall G:F, but the G:F of the multi-enzyme mixture-supplemented diets did not reach (P < 0.05) that of PC diet. Multi-enzyme mixture tended to increase (P = 0.08) femur breaking strength. Multi-enzyme mixture increased (P < 0.05) the ATTD of GE for the NC2 diet, but unaffected the ATTD of GE for the NC1 diet. Multi-enzyme mixture decreased (P < 0.05) the relative abundance of the Cyanobacteria and increased (P < 0.05) relative abundance of Butyricicoccus in feces. Thus, the NE, SID AA, STTD P, and Ca could be lowered by about 7%, 7%, 49%, and 22%, respectively, in multi-enzyme mixture-supplemented diets without negative effects on bone mineralization of grow-finish pigs. However, multi-enzyme mixture supplementation may not fully restore G:F of the grow-finish pigs fed diets that have lower NE and SID AA contents than recommended by 7%. Since an increase in content of Butyricicoccus in intestine is associated with improved gut health, addition of the multi-enzyme mixture in diets for pigs can additionally improve their gut health.

A study evaluated the effects of supplementing a multi-enzyme mixture that contain fiber degrading enzymes and phytase on the growth performance, bone strength, and fecal microbial composition of grow-finish pigs fed corn-wheat-wheat bran-based diets. Five diets fed were a positive control (PC) diet, and two negative control (NC1 and NC2) diets without or with the multi-enzyme mixture. The PC diet was adequate in all nutrients and had greater available (net) energy and digestible amino content than NC1 diet or NC2 diet by 7%, and greater digestible P content than the NC1 diet (by 32%) and NC2 diet (by 50%). The diets were fed from 30 to 120 kg body weight. Feed efficiency for PC diet was greater than that for NC1 diet or NC2 diet. Multi-enzyme mixture improved feed efficiency, bone strength, and fecal concentration of beneficial micro-organisms (known as Butyricicoccus) for NC1 and NC2 diets. However, feed efficiency for the NC1 and NC2 diets did not reach that for the PC diet. Thus, multi-enzyme mixture can fully restore bone strength (but not feed efficiency) and improve health of grow-finish pigs fed corn-wheat-wheat bran-based diets in which available energy, amino acids, and P contents have been reduced by the afore-mentioned margins.

Determination of the Optimal Level of Dietary Zinc for Newly Weaned Pigs: A Dose-Response Study.

One hundred and eighty individually housed piglets with an initial body weight of 7.63 ± 0.98 kg (at 28 days of age) were fed a diet containing either 153, 493, 1022, 1601, 2052 or 2407 mg zinc/kg (added Zn as zinc oxide; ZnO) from day 0-21 post weaning to determine the optimal level of Zn for weaned piglets. Body weight, feed intake and faecal scores were recorded, and blood and faecal samples were collected. Dietary Zn content quadratically affected both feed intake and gain in the first two weeks, with an approximately 1400 mg Zn/kg diet and a Zn intake of 400 mg/day as the optimal levels. The relative risk of diarrhoea increased up to 60% at day 7 and 14 if serum Zn status dropped below the weaning level (767 µg/L), and maintain the weaning serum Zn status required approximately 1100 mg Zn/kg (166 mg Zn/day) during week 1. Blood markers of intestinal integrity (D-lactate and diamine oxidase) were unaffected by dietary Zn, and dietary Zn levels of 1022 and 1601 mg/kg did not affect the faecal numbers of total bacteria, Lactobacilli and E. Coli bacteria compared to 153 mg Zn/kg. These results indicate that the requirement for Zn in newly weaned piglets may be substantially higher than currently assumed.

Net energy value of canola meal, field pea, and wheat millrun fed to growing-finishing pigs.

Two experiments were conducted to (1) determine net energy (NE) values of soybean meal (SBM), Napus canola meal (NCM), Juncea canola meal (JCM), field pea, and wheat millrun (WM) using indirect calorimetry, and (2) compare the determined NE values with the calculated NE values of the same feedstuffs based on a prediction equation. In experiment 1, six ileal-cannulated barrows (31 kg) were fed five diets in 5 × 6 Youden square to give six replicates per diet. Diets were cornstarch-based diets containing SBM, NCM, JCM, field pea, or WM. The SBM was included as a reference. In experiment 2, six ileal-cannulated barrows (70 kg) were fed a N-free diet for determining energy digestibility and NE values of test feedstuffs fed in experiment 1 by difference method. The NE values of test feedstuffs were also calculated from the digestible energy (DE) values and analyzed macronutrient content of the test feedstuffs. On dry matter (DM) basis, SBM, NCM, JCM, field pea, and WM contained 51%, 41%, 42%, 28%, and 18% crude protein; 1.52%, 2.95%, 2.36%, 1.33%, and 3.12% ether extract; 2.93%, 0.14%, 1.44%, 36.7%, and 28.7% starch; and 5.30%, 21.0%, 13.4%, 9.49%, and 16.1% acid detergent fiber, respectively. The determined NE value for SBM (2.29 Mcal/kg) did not differ from that of NCM (1.72 Mcal/kg DM) or JCM (2.14 Mcal/kg DM). The NCM and JCM did not differ in NE value. Also, the determined NE value did not differ between field pea (2.00 Mcal/kg) and WM (2.55 Mcal/kg). The calculated NE values for SBM (2.18 Mcal/kg DM), NCM (1.73 Mcal/kg DM), and JCM (1.86 Mcal/kg DM) did not differ from the corresponding determined NE values of the same feedstuffs. However, the calculated NE value for field pea (2.51 Mcal/kg DM) was greater (P = 0.004) than the determined NE value of field pea, whereas the calculated NE value for WM (2.27 Mcal/kg DM) tended to be lower (P = 0.054) than the determined NE value of WM. In conclusion, the NE value for SBM and canola meals can be predicted based on the DE value and the macronutrient composition of the same feedstuffs. However, the NE value for field pea and WM may not be predicted precisely based on the DE value and the macronutrient composition of the same feedstuffs.

Growth performance, visceral organ weights, and gut health of weaned pigs fed diets with different dietary fiber solubility and lipid sources.

The objective of this study was to determine the interactive effects of dietary fiber solubility and lipid source on growth performance, visceral organ weights, gut histology, and gut microbiota composition of weaned pigs. A total of 280 nursery pigs [initial body weight (BW) = 6.84 kg] weaned at 21 d were housed in 40 pens (7 pigs/pen). The pigs were fed four diets (10 pens/diet) in a randomized complete block design in two phases: Phase 1 from 0 to 2 wk and Phase 2 from 2 to 5 wk. The diets were corn-soybean meal-based with either sugar beet pulp (SBP) or soybean hulls (SBH) as a fiber source and either soybean oil (SBO) or choice white grease (CWG) as a lipid source in a 2 × 2 factorial arrangement. The BW and feed intake were determined by phase, whereas visceral organ weights, intestinal histology, and gut microbial composition were determined at the end of the trial. Dietary fiber solubility and lipid source did not interact (P > 0.05) on average daily feed intake and average daily gain across all phases. However, the gain to feed ratio (G:F) for CWG-containing diets was lower (P < 0.05) than that for SBO-containing diets for Phase 1. Also, G:F for SBP-containing diets was lower (P < 0.05) than that for SBH-containing diets for Phase 1 and for the entire study period. Pigs fed SBP-containing diets had greater (P < 0.05) stomach weight, and tended to have greater (P < 0.10) small and large intestine weights relative to BW than those fed SBH-containing diets. Duodenal villous height to crypt depth ratio for CWG-based diets tended to be greater (P = 0.09) than that for SBO-based diets. Fiber solubility and lipid source interacted (P < 0.05) on relative abundance of Bacteroides in the colon such that the relative abundance of the Bacteroides for CWG was greater (P < 0.05) than that for the SBO in SBP-based diet, but not in SBH-based diet. Relative abundance of Butyricicoccus in the colon for SBH-based diet was greater (P < 0.05) than that for SBP-based diet. In conclusion, inclusion of SBH instead of SBP in corn-soybean meal-based diets for weaned pigs can result in increased feed efficiency and relative abundance of Butyricicoccus in the colon, which is associated with improved gut health. Also, inclusion of SBO instead of CWG in the diets for weaned pigs can result in improved feed efficiency during Phase 1 feeding; however, the pigs may recover from the low feed efficiency induced by dietary inclusion of CWG instead of SBO after Phase 1 feeding.

Growth performance and gut health of Escherichia coli-challenged weaned pigs fed canola meal-containing diet.

An experiment was conducted to evaluate the effects of including canola meal (CM) in diets for weaning pigs challenged with a F18 strain of Escherichia coli on growth performance and gut health. A total of 36 individually housed weaned pigs (initial body weight [BW] = 6.22 kg) were randomly allotted to one of the three diets (12 pigs/diet). The three diets were corn-soybean meal (SBM)-based basal diet (control diet) and the basal diet with 0.3% zinc oxide, 0.2% chlortetracycline, and 0.2% tiamulin (antibiotic diet) or with 20% CM diet. The diets were fed in two phases: Phase 1: days 0 to 7 and Phase 2: days 7 to 20. All pigs were given an oral dose of 2 × 109 CFU of F18 strain of E. coli on day 7. Fecal score was assessed daily throughout the trial. Dietary antibiotics increased (P < 0.05) overall average daily gain (ADG) and average daily feed intake (ADFI) compared by 48% and 47%, respectively. Dietary CM increased (P < 0.05) overall ADG and ADFI by 22% and 23%, respectively; but the ADG and ADFI values for CM-containing diet did not reach those for the antibiotics-containing diet. Dietary antibiotics reduced (P < 0.05) fecal score; however, dietary CM unaffected fecal score. Dietary antibiotics decreased (P < 0.05) liver weight per unit live BW by 16% at day 20, whereas dietary CM did not affect liver weight per unit live BW (29.2 vs. 28.6). Also, dietary antibiotics increased (P < 0.05) serum triiodothyronine and tetraiodothyronine levels for day 14, whereas dietary CM did not affect the serum level of these hormones. Dietary antibiotics reduced (P < 0.05) the number white blood cells and neutrophils by 38% and 43% at day 20, respectively, whereas dietary CM tended to reduce (P = 0.09) the number white blood cells by 19% at day 20. The number white blood cells for CM diet tended to be greater (P < 0.10) than that for antibiotics diet. The dietary antibiotics decreased (P < 0.05) the concentration of individual volatile fatty acids and hence of total volatile fatty acid in cecum by 61% at day 20, whereas dietary CM decreased (P < 0.05) cecal butyric acid concentration by 61% and tended to reduce (P < 0.10) total volatile fatty acid concentration by 30% at day 20. In conclusion, the dietary inclusion of 20% CM improved ADG and tended to reduce white blood cell counts. Thus, inclusion of CM in antibiotics-free corn-SBM-based diets for weaned pigs that are challenged with F18 strain of E. coli can result in their improved performance partly through a reduction of the inflammatory response.

Toxicity of Canola-Derived Glucosinolate Degradation Products in Pigs-A Review.

Canola co-products are widely included in swine diets as sources of proteins. However, inclusion of canola co-products in diets for pigs is limited by toxicity of glucosinolate degradation products. Aliphatic and aromatic glucosinolates are two major classes of glucosinolates. Glucosinolate degradation products derived from aliphatic glucosinolates (progoitrin) include crambene, epithionitriles, and goitrin, whereas indole-3-acetonitrile, thiocyanate, and indole-3-carbinol are the major aromatic glucosinolates (glucobrassicin)-derived degradation products. At acidic pH (<5.7), progoitrin is degraded by myrosinases to crambene and epithionitriles in the presence of iron, regardless of the presence of epithiospecifier protein (ESP), whereas progoitrin is degraded by myrosinases to goitrin in the absence of ESP, regardless of the presence of iron at neutral pH (6.5). Indole-3-acetonitrile is the major degradation product derived from glucobrassicin in the absence of ESP, regardless of the presence of iron at acidic pH (<4.0), whereas thiocyanate and indole-3-carbinol are the major glucobrassicin-derived degradation products in the absence of ESP, regardless of the presence of iron at neutral pH (7.0). In conclusion, the composition of glucosinolate degradation products is affected by parent glucosinolate composition and hindgut pH. Thus, toxicity of canola co-product-derived glucosinolates can be potentially alleviated by modifying the hindgut pH of pigs.

Soybean meal allergenic protein degradation and gut health of piglets fed protease-supplemented diets.

Two experiments were conducted to determine the effects of protease supplementation on degradation of soybean meal (SBM) allergenic proteins (glycinin and ß-conglycinin) and gut health of weaned pigs fed soybean meal-based diets. In experiment 1, 2 SBM samples from 2 different sources were subjected to porcine in vitro gastric degradation to determine the effects of protease (at 15,000 U/kg of feedstuff) on degradation of the soybean allergenic proteins. In experiment 2, 48 weaned pigs (body weight = 6.66 kg) were obtained in 2 batches of 24 pigs each. Pigs were individually housed in metabolic crates and fed 4 diets (12 pigs/diet). The diets were corn-based diet with SBM 1 or SBM 2 without or with protease at 15,000 U/kg of diet in 2 × 2 factorial arrangement. Diets were fed for 10 d and pigs were sacrificed on day 10 for measurement of small intestinal histomorphology, permeability of small intestine mounted in Ussing chambers, and serum concentration of pro-inflammatory cytokines. Two SBM sources (SBM 1 and SBM 2) contained 46.9% or 47.7% CP, 14.0% or 14.6% glycinin, and 9.90% or 10.3% ß-conglycinin, respectively. Protease and SBM source did not interact on any of the response criteria measured in the current study. Protease supplementation tended to increase (P = 0.069) the in vitro gastric degradation of glycinin. Protease supplementation tended to reduce (P = 0.099) fluorescein isothiocyanate dextran 4,000 Da (which is a marker probe for intestinal permeability) flow in jejunum, and reduced (P = 0.037) serum TNF-α concentration. Protease did not affect small intestinal histomorphology. In conclusion, protease tended to increase gastric degradation of glycinin and reduce gut permeability, and serum concentration of pro-inflammatory cytokines, indicating that the protease used in the current study can be added to SBM-based diets for weanling pigs to improve gut health.

Growth performance, nutrient digestibility, and fecal microbial composition of weaned pigs fed multi-enzyme supplemented diets.

A study determined the effects of supplementing corn-based diets for weaned pigs with multi-enzymes on growth performance, apparent total tract digestibility (ATTD) of nutrients, fecal score, and fecal microbial composition. A total of 132 pigs (initial body weight = 7.23 kg) that had been weaned at 21 d of age and fed a drug-free nursery diet for 7 d were housed in 33 pens of 4 barrows or gilts, blocked by body weight and gender, and fed 3 experimental diets at 11 pens per diet. The diets were corn-based diet without or with multi-enzyme A or B. Multi-enzyme A supplied 4,000 U of xylanase, 150 U of ß-glucanase, 3,500 U of protease, and 1,500 U of amylase per kilogram of diet. Multi-enzyme B was the same as multi-enzyme A except that it supplied amylase at 150 U/kg, and that its source of amylase was different from that of multi-enzyme A. All diets contained phytase at 1,000 U/kg. The diets were fed for 35 d in 2 phases; phase 1 for the first 14 d and phase 2 for the last 21 d of the trial. Fecal score was determined daily during the first 7 d of the trial. Fecal samples were collected from rectum of 1 pig per pen on days 2, 7, 14, and 35 of the trial for determining bacterial composition. Also, fresh fecal samples were collected from each pen on days 41 and 42 to determine ATTD of nutrients. Multi-enzyme B increased (P < 0.05) average daily gain (ADG) for phases 1 and 2. For the overall study period, multi-enzyme B increased (P < 0.05) ADG from 262 to 313 g, and average daily feed intake (ADFI) from 419 to 504 g. Multi-enzyme A increased (P < 0.05) overall ADG from 262 to 290 g, but did not affect ADFI. Multi-enzyme A or B did not affect ATTD of gross energy, but increased (P < 0.05) the ATTD of ether extract from 30% to 36% or 37%, respectively. Multi-enzyme A did not affect fecal score; however, multi-enzyme B tended to decrease (P = 0.09) fecal score, implying that it tended to decrease diarrhea. Firmicutes were the most abundant phylum of fecal bacteria (its relative abundance ranged from 58% to 72%). Bacteroidetes and Actinobacteria were the 2nd and 3rd most abundant phyla of fecal bacteria. Neither multi-enzyme affected fecal bacterial composition. In conclusion, the addition of multi-enzyme A or B to phytase-supplemented corn-based diet for weaned pigs can improve their growth performance and fat digestibility. However, multi-enzyme B was more effective than multi-enzyme A in terms of improving the growth performance of weaned pigs fed corn-based diet.

Canola meal in nursery pig diets: growth performance and gut health.

An experiment was conducted to determine the effects of including canola meal (CM) in nursery pig diets on growth performance, immune response, fecal microbial composition, and gut integrity. A total of 200 nursery pigs (initial body weight = 7.00 kg) were obtained in two batches of 100 pigs each. Pigs in each batch were housed in 25 pens (four pigs per pen) and fed five diets in a randomized complete block design. The five diets were corn-soybean meal (SBM)-based basal diets with 0%, 10%, 20%, 30%, or 40% of CM. The diets were fed in three phases: phase 1: day 0 to 7, phase 2: day 7 to 21, and phase 3: day 21 to 42. Diets in each phase were formulated to similar net energy, Ca, and digestible P and amino acid contents. Feed intake and body weight were measured by phase. Immune response and gut integrity parameters were measured at the end of phases 1 and 2. Fecal microbial composition for diets with 0% or 20% CM was determined at the end of phase 2. Overall average daily gain (ADG) responded quadratically (P < 0.05) to increasing dietary level of CM such that ADG was increased by 17% due to an increase in the dietary level of CM from 0% to 20% and was reduced by 16% due to an increase in the dietary level of CM from 20% to 40%. Pigs fed diets with 0% or 40% CM did not differ in overall ADG. Dietary CM tended to quadratically decrease (P = 0.09) serum immunoglobulin A (IgA) level at the end of phase 2 such that serum IgA level tended to reduce with an increase in dietary CM from 0% to 20% and to increase with an increase in dietary CM from 20% to 40%. Dietary CM at 20% decreased (P < 0.05) the relative abundance of Bacteroidetes phylum and tended to increase (P = 0.07) the relative abundance of Firmicutes phylum. Dietary CM linearly increased (P < 0.05) the lactulose to mannitol ratio in the urine by 47% and 49% at the end of phases 1 and 2, respectively, and tended to linearly decrease (P < 0.10) ileal transepithelial electrical resistance at the end of phase 1 by 64%. In conclusion, CM fed in the current study could be included in corn-SBM-based diets for nursery pigs 20% to improve the growth performance and gut microbial composition and reduce immune response. Also, the CM used in the current study could be included in corn-SBM-based diets for nursery pigs at 30% or 40% without compromising growth performance. Dietary CM increased gut permeability, implying that dietary CM at 20% improves the growth performance of weaned pigs through mechanisms other than reducing gut permeability.

Toxicity of canola-derived glucosinolates in pigs fed resistant starch-based diets.

A study was conducted to determine effects of reducing hindgut pH through dietary inclusion of high-amylose cornstarch (HA-starch) on growth performance, organ weights relative to live body weight (BW), blood thyroid hormone levels, and glucosinolate degradation products of nursery pigs fed cold-pressed canola cake (CPCC). A total of 240 pigs (initial BW: 7.1 kg), which had been weaned at 21 d of age, were housed in 40 pens (6 pigs per pen) and fed 4 diets (10 pens per diet) in a randomized complete block design for 28 d. Four diets were a basal diet with CPCC at 0 or 40%, and with HA-starch at 0 or 40% in a 2 × 2 factorial arrangement. The diets were fed in two phases: Phase 1 from day 0 to 14 and Phase 2 from day 14 to 28 and were formulated to have the same net energy, standardized ileal digestible AA, Ca, and standardized total tract digestible P contents. Dietary inclusion of CPCC and HA-starch was achieved by a partial or complete replacement of corn, soybean meal, and soy protein. At the end of the study, one pig from each pen was euthanized to determine organ weights, blood parameters, hindgut pH, and glucosinolate degradation products. Dietary CPCC reduced (P < 0.05) overall average daily gain (ADG) by 15%; increased (P < 0.05) relative weights of liver and thyroid gland by 27% and 64%, respectively; and reduced (P < 0.05) serum tetraiodothyronine (T4) level from 30.3 to 17.8 ng/mL. Heart, kidney, and gastrointestinal tract weights; serum triiodothyronine level; and hindgut pH of pigs were unaffected by dietary CPCC. Dietary HA-starch reduced (P < 0.05) overall ADG, relative weight of thyroid gland, cecal, and colonic pH; but increased (P < 0.05) relative weight of colon; tended to increase (P = 0.062) serum T4 level. Dietary CPCC and HA-starch interacted (P = 0.024) on relative weight of thyroid gland such that dietary CPCC increased (P < 0.05) weight of thyroid gland for HA-starch-free diet (120 vs. 197 mg/kg of BW) but not for HA-starch-containing diet (104 vs. 130 mg/kg of BW). Dietary CPCC and HA-starch interacted (P = 0.001) on cecal isothiocyanate content such that dietary CPCC increased (P < 0.05) level of isothiocyanates for HA-starch-containing diet but not for HA-starch-free diet. In conclusion, dietary CPCC reduced growth performance, increased liver, size and interfered with thyroid gland functions of pigs. However, the negative effects of dietary CPCC on thyroid gland functions of nursery pigs were alleviated by dietary HA-starch.

Growth performance and gut health of Escherichia coli-challenged weaned pigs fed diets supplemented with a Bacillus subtilis direct-fed microbial.

This study was conducted to investigate the effects of a direct-fed microbial (DFM) product (Bacillus subtilis strain DSM 32540) in weaned pigs challenged with K88 strain of Escherichia coli on growth performance and indicators of gut health. A total of 21 weaned pigs [initial body weight (BW) = 8.19 kg] were housed individually in pens and fed three diets (seven replicates per diet) for 21 d in a completely randomized design. The three diets were a corn-soybean meal-based basal diet without feed additives, a basal diet with 0.25% antibiotics (neo-Oxy 10-10; neomycin + oxytetracycline), or a basal diet with 0.05% DFM. All pigs were orally challenged with a subclinical dose (6.7 × 108 CFU/mL) of K88 strain of E. coli on day 3 of the study (3 d after weaning). Feed intake and BW data were collected on days 0, 3, 7, 14, and 21. Fecal scores were recorded daily. On day 21, pigs were sacrificed to determine various indicators of gut health. Supplementation of the basal diet with antibiotics or DFM did not affect the overall (days 0-21) growth performance of pigs. However, antibiotics or DFM supplementation increased (P = 0.010) gain:feed (G:F) of pigs during the post-E. coli challenge period (days 3-21) by 23% and 24%, respectively. The G:F for the DFM-supplemented diet did not differ from that for the antibiotics-supplemented diet. The frequency of diarrhea for pigs fed a diet with antibiotics or DFM tended to be lower (P = 0.071) than that of pigs fed the basal diet. The jejunal villous height (VH) and the VH to crypt depth ratio (VH:CD) were increased (P < 0.001) by 33% and 35%, respectively, due to the inclusion of antibiotics in the basal diet and by 43% and 41%, respectively due to the inclusion of DFM in the basal diet. The VH and VH:CD for the DFM-supplemented diet were greater (P < 0.05) than those for the antibiotics-supplemented diet. Ileal VH was increased (P < 0.05) by 46% due to the inclusion of DFM in the basal diet. The empty weight of small intestine, cecum, or colon relative to live BW was unaffected by dietary antibiotics or DFM supplementation. In conclusion, the addition of DFM to the basal diet improved the feed efficiency of E. coli-challenged weaned pigs to a value similar to that of the antibiotics-supplemented diet and increased jejunal VH and VH:CD ratio to values greater than those for the antibiotics-supplemented diet. Thus, under E. coli challenge, the test DFM product may replace the use of antibiotics as a growth promoter in diets for weaned pigs to improve feed efficiency and gut integrity.

Growth performance and nutrient digestibility of growing and finishing pigs fed multienzyme-supplemented low-energy and -amino acid diets.

A study was conducted to determine the effects of supplementing corn-soybean meal-based diets with a multienzyme on growth performance, bone mineralization, apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of nutrients of growing pigs. A total of 276 pigs (body weight [BW] = 33.99 ± 4.3 kg) were housed by sex in 45 pens of 6 or 7 pigs and fed 5 diets (9 pens/diet) in a randomized complete block design. Diets were positive control (PC); and negative control 1 (NC1) or negative control 2 (NC2) without or with multienzyme. The multienzyme used supplied at least 1,800, 1,244, 6,600, and 1,000 units of xylanase, ß-glucanase, arabinofuranosidase, and phytase per kilogram of diet, respectively. The PC diet was adequate in all nutrients according to NRC recommendations and had greater digestible P content than NC1 or NC2 diet by 0.134 percentage points. The PC diet had greater net energy (NE) and standardized ileal digestible amino acids (AA) content than NC1 diet by 3%, and than NC2 diet by 5%. The diets were fed in 4 phases based on BW: Phase 1: 34-50 kg; Phase 2: 50-75 kg; Phase 3: 75-100 kg; and Phase 4: 100-120 kg. Nutrient digestibility and bone mineralization were determined at the end of Phase 1. Overall (34-120 kg BW), pigs fed the PC and NC1 diets did not differ in average daily gain (ADG) and average daily feed intake. Pigs fed NC2 diet had lower (P < 0.05) ADG and gain-to-feed ratio (G:F) than those fed PC diet. Pigs fed PC diet had greater (P < 0.05) bone ash content and ATTD of P than those fed NC1 diet. The ATTD of GE for PC diet was greater (P < 0.05) than that for NC2 diet, and tended to be greater (P < 0.10) than that for NC1 diet. Multienzyme interacted (P < 0.05) with negative control diet type on overall ADG and AID of GE such that multienzyme did not affect overall ADG and AID of GE for the NC1 diet, but increased (P < 0.05) overall ADG and AID of GE for NC2 diet by 5.09 and 8.74%, respectively. Multienzyme did not interact with negative control diet type on overall G:F, bone ash content, AID of AA, and ATTD of nutrients. Multienzyme increased (P < 0.05) overall G:F, AID of methionine, ATTD of GE and P, and tended to increase (P = 0.056) bone ash content. The ADG, bone ash content, and ATTD of GE and P for the multienzyme-supplemented diets were similar to (P > 0.10) PC diet. Thus, NE and digestible AA and P can be lowered by ≤5% in multienzyme-supplemented diets without effects on growth performance and bone ash of pigs.

Ileal digestibility and endogenous flow of minerals and amino acids: responses to dietary phytic acid in piglets.

Effects of phytic acid (PA) on ileal mineral and amino acid (AA) digestibilities and ileal endogenous AA flow in piglets were investigated. Seven ileal-cannulated weanling pigs were fed a casein-maize starch-based diet with PA (as sodium phytate) at 0, 5, 10 or 20 g/kg in 4 x 4 Latin square design with three added columns to give seven observations per treatment. The basal diet was formulated to meet National Research Council energy and AA requirements for piglets. The respective digestibility and endogenous lysine loss were determined by indicator and homoarginine methods. The apparent ileal digestibility (AID) of Na, K and P was linearly and quadratically reduced (P < 0.05) by increased dietary PA concentration, whereas that of Ca and Mg was only linearly reduced (P < 0.05) by the dietary PA. The AID values for Mg and Na were negative ( - 0.03 and - 0.18, respectively) when PA was supplemented at 20 g/kg. The AID of isoleucine, leucine and valine responded quadratically to dietary PA concentration, though the differences between the AID values of the AA due to change in dietary PA concentration were marginal (at most by 1.8 percentage units). Furthermore, dietary PA did not affect (P>0.05) endogenous AA losses. The results suggest that PA has limited effect on the digestibility and endogenous losses of AA in piglets, but can reduce AID of Mg and Na partly by increasing endogenous losses of these minerals as evidenced by their negative AID values.

Nutritive value of enzyme-supplemented carinata meal for growing pigs.

Carinata meal is increasingly available for livestock feeding. However, the effects of supplemental phytase and fiber degrading enzymes on nutritive value of carinata meal for pigs have not been reported. Objective of the study was to evaluate the standardized ileal digestibility (SID) of amino acid (AA), and digestible energy (DE) and net energy (NE) values of phytase- and fiber-degrading enzymes-supplemented carinata meal for growing pigs. Ten ileal-cannulated pigs (initial body weight = 53.9 ± 4.76 kg) were fed 4 diets in a replicated 4 × 4 Latin square design with two additional columns to give 10 replicates per diet. Diets included a corn-soybean meal (SBM)-based basal diet, basal diet with 25% carinata meal, basal diet with 25% carinata meal plus phytase at 2,000 FTU/kg and multi-carbohydrase at 0.2 g/kg, and in addition a nitrogen-free diet. The multicarbohydrase supplied 4 units of xylanase, 10 units of ß-glucanase, and 1,000 units of pectinase per kilogram of diet. The ratio of corn to SBM and soybean oil in carinata meal-containing diets was identical to that in the corn-SBM-based basal diet to allow calculation of AA and energy digestibility of carinata meal by the difference method. On a dry matter basis, carinata meal contained 50.2% crude protein, 0.88% ether extract, 15.37% acid detergent fiber, 1.82% Lys, 0.96% Met, 1.89% Thr, and 0.64% Trp, respectively. The SID of Lys, Met, Thr, and Trp for carinata meal were 51.4%, 82.2%, 65.9%, and 85.9%, respectively. The DE and NE values for carinata meal were 3,427 and 1,828 kcal/kg of dry matter, respectively. Supplementation of a combination of phytase and multicarbohydrase did not affect the apparent ileal digestibility of AA and SID of AA for the corn-SBM-carinata meal-based diet, and for the carinata meal. However, the combination of phytase and multicarbohydrase did improve (P < 0.05) apparent total tract digestibility, and DE and NE values for carinata meal by 9.4%, 9.5%, and 12.4%, respectively. In conclusion, the enzymes used in the current study could be added in carinata meal-based diets for growing pigs to improve the energy value.