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Analysis of Gastrointestinal Responses Revealed Both Shared and Specific Targets of Zinc Oxide and Carbadox in Weaned Pigs.

ABSTRACT: Antibiotics and pharmacological zinc supplementation were commonly used as growth promoters for several decades in the swine industry before being limited because of public health and environmental concerns. Further, the physiological and metabolic responses associated with their growth promotion effects are unclear. To characterize these responses induced by pharmacological zinc supplementation (2500 mg/kg) and carbadox (55 mg/kg), 192 post-weaning pigs were fed basal and test diets for 43 days. Compared with basal, pharmacological zinc and carbadox independently improved growth performance. Pharmacological zinc increased gastric mucosa thickness compared with basal zinc, while carbadox increased intestinal villus:crypt ratio compared with non-carbadox. Pharmacological zinc and carbadox independently reduced interleukin (IL)-1? concentration compared with basal zinc and non-carbadox. Pharmacological zinc increased IL-1RA:IL-1 ratio by 42% compared with basal zinc, while carbadox tended to increase the IL-10 and IL10:IL-12 ratio compared with non-carbadox. Carbadox increased fecal concentrations of histidine and lysine compared with non-carbadox. The independent effect of pharmacological zinc and carbadox on morphology and nutrient metabolism, and their shared effect on immunity may contribute to the additive effect on growth promotion. These results further confirmed the concept that growth promotion is multifactorial intervention. Therefore, elucidating growth-promoting effects and searching for alternatives should include wide-spectrum evaluation.

SUBMITTER: Hung YT

PROVIDER: S-EPMC7460413 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Analysis of Gastrointestinal Responses Revealed Both Shared and Specific Targets of Zinc Oxide and Carbadox in Weaned Pigs.

Hung Yuan-Tai YT Hu Qiong Q Faris Richard J RJ Guo Juanjuan J Urriola Pedro E PE Shurson Gerald C GC Chen Chi C Saqui-Salces Milena M

Antibiotics (Basel, Switzerland) 20200730 8

Antibiotics and pharmacological zinc supplementation were commonly used as growth promoters for several decades in the swine industry before being limited because of public health and environmental concerns. Further, the physiological and metabolic responses associated with their growth promotion effects are unclear. To characterize these responses induced by pharmacological zinc supplementation (2500 mg/kg) and carbadox (55 mg/kg), 192 post-weaning pigs were fed basal and test diets for 43 days ...[more]

PMID: 32751572

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Project description:The study was conducted to investigate the efficacy of a probiotic Bacillus subtilis strain on growth performance, diarrhea, systemic immunity, and intestinal health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli and to compare the efficacy of B. subtilis with that of carbadox. Weaned pigs (n = 48, 6.17 ± 0.36 kg body weight [BW]) were individually housed in disease containment rooms and randomly allotted to one of four dietary treatments: negative control (NC, control diet without E. coli challenge), positive control (PC, control diet with E. coli challenge), and supplementation of 50 mg/kg of carbadox (antibiotic growth promotor [AGP]) or 2.56 × 109 CFU/kg of B. subtilis probiotics (PRO). The experiment lasted for 28 d with 7 d before and 21 d after the first E. coli inoculation. Fecal and blood samples were collected on days 0, 3, 7, 14, and 21 post inoculation (PI) to analyze β-hemolytic coliforms and complete blood cell count, respectively. Diarrhea score was recorded daily for each pig to calculate the frequency of diarrhea. All pigs were euthanized at day 21 PI to collect jejunal and ileal mucosa for gene expression analysis. Pigs in AGP had greater (P < 0.05) BW on days 7, 14, and 21 PI than pigs in PC and PRO groups. Supplementation of PRO enhanced pigs' BW on day 21 PI compared with the PC. Escherichia coli F18 challenge reduced (P < 0.05) average daily gain (ADG) and feed efficiency from day 0 to 21 PI, while supplementation of carbadox or PRO enhanced ADG and feed efficiency in E. coli F18-challenged pigs from day 0 to 21 PI. Pigs in AGP and PRO groups had reduced (P < 0.05) frequency of diarrhea throughout the experiment and fecal β-hemolytic coliforms on day 7 PI than pigs in the PC. Pigs in PRO had greater (P < 0.05) gene expression of CLDN1 in jejunal mucosa than pigs in the PC. Supplementation of carbadox or PRO reduced (P < 0.05) the gene expression of IL6 and PTGS2 in ileal mucosa of E. coli-infected pigs compared with pigs in the PC. Pigs in the PRO group had lower (P < 0.05) white blood cell number and neutrophil count, and serum haptoglobin concentration on day 7 PI, and less (P < 0.05) monocyte count on day 14 PI, compared with PC. In conclusion, supplementation of probiotic B. subtilis could enhance disease resistance and promote the growth performance of weaned pigs under disease challenge conditions. The potential mechanisms include but not limited to enhanced gut barrier integrity and local and systemic immune responses of weaned pigs.

Project description:Strategies to reduce economic losses associated with post-weaning diarrhea in pig farming include high-level dietary zinc oxide supplementation. However, excessive usage of zinc oxide in the pig production sector was found to be associated with accumulation of multidrug resistant bacteria in these animals, presenting an environmental burden through contaminated manure. Here we report on zinc tolerance among a random selection of intestinal Escherichia coli comprising of different antibiotic resistance phenotypes and sampling sites isolated during a controlled feeding trial from 16 weaned piglets: In total, 179 isolates from "pigs fed with high zinc concentrations" (high zinc group, [HZG]: n = 99) and a corresponding "control group" ([CG]: n = 80) were investigated with regard to zinc tolerance, antimicrobial- and biocide susceptibilities by determining minimum inhibitory concentrations (MICs). In addition, in silico whole genome screening (WGSc) for antibiotic resistance genes (ARGs) as well as biocide- and heavy metal tolerance genes was performed using an in-house BLAST-based pipeline. Overall, porcine E. coli isolates showed three different ZnCl2 MICs: 128 μg/ml (HZG, 2%; CG, 6%), 256 μg/ml (HZG, 64%; CG, 91%) and 512 μg/ml ZnCl2 (HZG, 34%, CG, 3%), a unimodal distribution most likely reflecting natural differences in zinc tolerance associated with different genetic lineages. However, a selective impact of the zinc-rich supplemented diet seems to be reasonable, since the linear mixed regression model revealed a statistically significant association between "higher" ZnCl2 MICs and isolates representing the HZG as well as "lower ZnCl2 MICs" with isolates of the CG (p = 0.005). None of the zinc chloride MICs was associated with a particular antibiotic-, heavy metal- or biocide- tolerance/resistance phenotype. Isolates expressing the 512 μg/ml MIC were either positive for ARGs conferring resistance to aminoglycosides, tetracycline and sulfamethoxazole-trimethoprim, or harbored no ARGs at all. Moreover, WGSc revealed a ubiquitous presence of zinc homeostasis and - detoxification genes, including zitB, zntA, and pit. In conclusion, we provide evidence that zinc-rich supplementation of pig feed selects for more zinc tolerant E. coli, including isolates harboring ARGs and biocide- and heavy metal tolerance genes - a putative selective advantage considering substances and antibiotics currently used in industrial pork production systems.

Project description:BackgroundThe high doses of zinc oxide (ZnO) administered orally to piglets for the prevention of diarrhea and increase of growth rate can contaminate pig farms and the surrounding environment. Therefore, there is a need to find a replacement of high doses of dietary ZnO with an equally effective alternative. In the present study, the effect of two formulations of zinc phosphate-based nanoparticles (ZnA and ZnC NPs) on growth performance, intestinal microbiota, antioxidant status, and intestinal and liver morphology was evaluated. A total of 100 weaned piglets were randomly divided into 10 equal groups with the base diet (control) or the base diet supplemented with ZnA, ZnC, or ZnO at concentrations 500, 1000, and 2000?mg Zn per kilogram of diet. Supplements were given to animals for 10?days. Fecal samples were collected on day 0, 5, 10 and 20. At the end of the treatment (day 10), three piglets from each group were sacrificed and analyzed.ResultsComparing to that of control, the significantly higher piglet weight gain was observed in all piglet groups fed with ZnA (P?<?0.05). Differences in the total aerobic bacteria and coliform counts in piglet feces after NPs supplementation compared to that of control and ZnO groups were also found (P?<?0.05). The majority of aerobic culturable bacteria from the feces represented Escherichia (28.57-47.62%), Enterococcus (3.85-35.71%), and Streptococcus (3.70-42.31%) spp. A total of 542 Escherichia coli isolates were screened for the virulence genes STa, STb, Stx2, F4, and F18. The substantial occurrence of E. coli virulence factors was found on day 5, mainly in fimbrillary antigen and thermostable toxins, except for piglets fed by ZnC. Zn treatment decreased Zn blood levels in piglets fed with ZnO and ZnA (500?mg/kg) and increased in ZnC (2000?mg/kg) compared to that of control (P?<?0.05). The antioxidant status of piglets was affected only by ZnA. While some changes in the liver and the intestinal morphology of piglets with NPs were observed, none were serious as reflected by the normal health status and increased weigh gain performance.ConclusionsOur results indicate that ZnA NPs have a positive effect on the piglet growth performance even at the lowest concentration. The prevalence of E. coli virulence factors was lowest in pigs supplemented with ZnC. Zinc phosphate-based nanoparticles may be an effective alternative to ZnO.

Dataset Information

Analysis of Gastrointestinal Responses Revealed Both Shared and Specific Targets of Zinc Oxide and Carbadox in Weaned Pigs.

Publications

Analysis of Gastrointestinal Responses Revealed Both Shared and Specific Targets of Zinc Oxide and Carbadox in Weaned Pigs.

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