Advances on Alternatives to Conventional Antimicrobials: Implications on Livestock, Aquaculture, and Poultry Production

A special issue of Animals (ISSN 2076-2615).

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 24840

Special Issue Editor


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Guest Editor
Poultry Production and Product Safety Research Unit (PPPSRU), USDA-ARS, University of Arkansas, Fayetteville, AR 72701, USA
Interests: foodborne pathogens; adaptive and innate immunity; irradiation; vaccines; food safety; metagenomics; antimicrobial resistance; microbiome; diet; phytochemicals; probiotics; prebiotics; organic acids
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Special Issue Information

Dear Colleagues,

Conventional antibiotics have been in use for several decades and have saved millions of lives in both humans and animals. However, due to the emergence of antibiotic-resistant bacteria, the application of antibiotics has been restricted or banned. Recently, C. perfringens has been classified as one of the major foodborne pathogens in the United States. Antibiotics had been used by the poultry industry to control necrotic enteritis (NE) caused by Clostridium perfringens, but the ban of antibiotic use in poultry has not only increased the incidence of NE but has also increased the incidence of foodborne outbreaks caused by C. perfringens, making it pivotal to develop alternatives to control the pathogen. Several research groups are involved in the discovery of novel alternative approaches to control bacterial/viral pathogens in various environments including livestock, aquaculture, and poultry, which are reservoirs for several foodborne bacterial pathogens.

The aim of this Special Issue is to provide a collection of articles that showcase current issues and the research addressed by the title, “Advances on Alternatives to Conventional Antimicrobials: Implications on Livestock, Aquaculture, and Poultry Production”. As Guest Editor of this Special Issue, I invite you to submit original research articles, review articles, and short communications related to the control of bacterial or viral pathogens in animals, birds, and aquatic animals.

Dr. Palmy Jesudhasan
Guest Editor

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Keywords

  • phytochemicals
  • antiviral compounds
  • Salmonella
  • Campylobacter
  • Clostridium
  • natural feed additives
  • poultry
  • swine
  • microbiome
  • metagenomics
  • toxins
  • emerging pathogens
  • antibiotic resistance
  • phage therapy
  • animal health
  • aquaculture
  • poultry health

Published Papers (11 papers)

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Research

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8 pages, 885 KiB  
Communication
A Multiomic Analysis of Chicken Serum Revealed the Modulation of Host Factors Due to Campylobacter jejuni Colonization and In-Water Supplementation of Eugenol Nanoemulsion
by Basanta R. Wagle, Austin Quach, Seungjun Yeo, Anna L. F. V. Assumpcao, Komala Arsi, Annie M. Donoghue and Palmy R. R. Jesudhasan
Animals 2023, 13(4), 559; https://doi.org/10.3390/ani13040559 - 05 Feb 2023
Viewed by 1218
Abstract
Campylobacter jejuni is a foodborne pathogen that causes campylobacteriosis globally, affecting ~95 million people worldwide. Most C. jejuni infections involve consuming and/or handling improperly cooked poultry meat. To better understand chicken host factors modulated by Campylobacter colonization, we explored a novel LCMS-based multiomic [...] Read more.
Campylobacter jejuni is a foodborne pathogen that causes campylobacteriosis globally, affecting ~95 million people worldwide. Most C. jejuni infections involve consuming and/or handling improperly cooked poultry meat. To better understand chicken host factors modulated by Campylobacter colonization, we explored a novel LCMS-based multiomic technology using three experimental groups: (1) negative control, (2) positive control, and (3) eugenol nanoemulsion (EGNE) treatment (supplemented with 0.125% EGNE in the water) of broiler chickens (n = 10 birds/group). Birds in groups two and three were challenged with C. jejuni on day 7, and serum samples were collected from all groups on day 14. Using this multiomic analysis, we identified 1216 analytes (275 compounds, seven inorganics, 407 lipids, and 527 proteins). The colonization of C. jejuni significantly upregulated CREG1, creatinine, and 3-[2-(3-Hydroxyphenyl) ethyl]-5-methoxyphenol and downregulated sphingosine, SP d18:1, high mobility group protein B3, phosphatidylcholines (PC) P-20:0_16:0, PC 11:0_26:1, and PC 13:0_26:2. We found that 5-hydroxyindole-3-acetic acid significantly increased with the EGNE treatment when compared to the positive and negative controls. Additionally, the treatment increased several metabolites when compared to the negative controls. In conclusion, this study revealed several potential targets to control Campylobacter in broiler chickens. Full article
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12 pages, 612 KiB  
Article
Alleviation of Catching and Crating Stress by Dietary Supplementation of Bacillus subtilis in Pekin Ducks
by Helen Mitin, Idrus Zulkifli, Muhammad Hazim Che Jamri, Nur Athirah Zamzuri, Nurain Aliah Samian, Aimi Nabilah Hussein, Yong Meng Goh and Awis Qurni Sazili
Animals 2022, 12(24), 3479; https://doi.org/10.3390/ani12243479 - 09 Dec 2022
Cited by 1 | Viewed by 1280
Abstract
Catching and crating may elicit stress and fear reactions in poultry because the procedures involve human contact and exposure to a novel environment. This study determined the effects of dietary probiotic supplementation on physiological stress, underlying fear, and growth performance of Pekin ducks [...] Read more.
Catching and crating may elicit stress and fear reactions in poultry because the procedures involve human contact and exposure to a novel environment. This study determined the effects of dietary probiotic supplementation on physiological stress, underlying fear, and growth performance of Pekin ducks subjected to catching and 4 h of crating. The study used a 2 × 2 factorial arrangement; the main factors were diet (basal or basal + probiotic) and crating durations (0 or 4 h). From 1 to 21 days of age (doa), birds were fed a basal or basal + probiotic (CLOSTAT® (Bacillus subtilis) (Kemin Industries, Inc., Des Moines, IA, USA), 1 g/kg) diet. At 21 doa, an equal number of ducklings from each dietary group were caught and crated for 4 h or left undisturbed in the home pens. Birds were examined for serum corticosterone (CORT), heat shock protein (HSP) 70, creatine kinase (CK), triglyceride (TG), glucose (GLU), cholesterol (CHOL), and lactate (LAC) concentrations, heterophil to lymphocyte ratios (HLR), tonic immobility (TI) duration, open-field (OF) test, body weight (BW), and feed conversion ratios (FCR). Diet had no significant (p > 0.05) effect on CORT among the non-crated ducks. However, after catching and crating, birds fed the control diet had significantly (p < 0.05) higher CORT than their probiotic-supplemented counterparts. Catching and crating significantly (p < 0.05) elevated HSP70, HLR, GLU, and CHOL but reduced TG in ducks. Birds fed the probiotic-supplemented diet showed significantly (p < 0.05) lower HSP70, HLR, TG, and CK than those fed the control diet. Probiotic-supplemented ducks showed reduced fear-related behaviours, including TI durations, ambulation latency, and body shaking. Diet had a negligible effect on body weights and FCR of ducks at 21 doa. In brief, catching and crating for 4 h augmented Pekin ducks’ physiological stress and fear reactions, and supplementing birds with probiotics was beneficial in ameliorating these detrimental effects. Full article
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8 pages, 247 KiB  
Article
Effect of Oxidized β-Carotene on Swine Growth Performance under Commercial Production Conditions in Vietnam
by La Van Kinh, William W. Riley, James G. Nickerson, La Thi Thanh Huyen and Graham W. Burton
Animals 2022, 12(22), 3200; https://doi.org/10.3390/ani12223200 - 18 Nov 2022
Cited by 1 | Viewed by 1326
Abstract
The effects of oxidized β-carotene (OxBC) were determined upon the growth performance of swine through their full growth cycle under commercial production conditions in Vietnam. Five hundred 28-day-old-weaned barrows and gilts were used in a 140-day complete wean-to-finish feeding trial. Animals were randomized [...] Read more.
The effects of oxidized β-carotene (OxBC) were determined upon the growth performance of swine through their full growth cycle under commercial production conditions in Vietnam. Five hundred 28-day-old-weaned barrows and gilts were used in a 140-day complete wean-to-finish feeding trial. Animals were randomized by weight, and each pen contained 20 pigs with the same ratio of barrows to gilts. There were five dietary treatment groups with five replicate pens per treatment: Control basal diet, no antibiotics or OxBC; Basal diet with antibiotics; no OxBC; Basal diet supplemented with 2, 4, or 8 mg OxBC/kg of diet, no antibiotics. Growth performance parameters were calculated for each production stage (Starter: Days 1–28, Grower: Days 29–84, Finisher: Days 85–140) and for the overall study (Days 1–140). OxBC and antibiotics each improved growth rate, feed efficiency, and body weight compared to the unsupplemented control (p < 0.001). Animals receiving 4 and 8 mg/kg OxBC performed better than animals on antibiotics (p < 0.001). In Starter pigs, OxBC reduced the occurrence of diarrhea dose-dependently (2, 4, and 8 mg/kg) and more so than did antibiotics (p < 0.001). These findings support the concept that oxidized β-carotene can facilitate swine growth and health in the absence of in-feed antibiotics. Full article
8 pages, 277 KiB  
Article
In Vivo Efficacy of Echinops spinosus Decoction as a Therapeutic for Cows at Risk of Clinical Endometritis
by Saleh Boudelal, Mounir Adnane, Abdelatif Niar and Aspinas Chapwanya
Animals 2022, 12(21), 2975; https://doi.org/10.3390/ani12212975 - 29 Oct 2022
Cited by 2 | Viewed by 1617
Abstract
Clinical endometritis (CE) is a multifactorial disease of dairy animals. Retained fetal membranes (RFM) and metritis are the major risk factors of CE in dairy cows. Because uterine inflammation affects the profitability of the dairy industry, antibiotics and hormonal therapies are commonly used [...] Read more.
Clinical endometritis (CE) is a multifactorial disease of dairy animals. Retained fetal membranes (RFM) and metritis are the major risk factors of CE in dairy cows. Because uterine inflammation affects the profitability of the dairy industry, antibiotics and hormonal therapies are commonly used to mitigate against the disease. However, the One-Health concept aims to reduce antibiotic use in food animals to avoid the emergence of drug resistance or residues in milk or meat. Thus, phytotherapy may represent a good alternative to antibiotics in food animals. Echinops spinosus (E. spinosus) is a natural plant known to have therapeutic, anti-inflammatory, antimicrobial, and wound-healing properties in vitro. The aim of the present study was to investigate the efficacy of E. spinosus as a preventive strategy for CE in dairy cows with other postpartum complications. Holstein–Friesian cows (n = 36) diagnosed with RFM or metritis enrolled in the study were allocated into three groups. One group received antibiotic treatment. Another group received prostaglandin injection (PG). The experimental group received E. spinosus decoction orally. As a control group, eutocic cows (n = 36), without RFM and metritis were included in the study. The efficiency of the treatment was based on the occurrence of CE and improved reproductive outcomes. At 30 ± 2 DPP, CE was diagnosed in 25%, 58.34%, and 75% in antibiotic, PG, and E. spinosus groups, respectively (p < 0.05). There were no differences between the groups at 55 ± 5 DPP (16.67%, 33.44%, and 41.67% in antibiotic, PG and E. spinosus groups, respectively, p > 0.05). The E. spinosus group had the longest open days, lowest conception rate at 150 DPP, and highest number of services per conception. Oral E. spinosus extract is ineffective as a therapeutic for cows at risk of CE. These findings may pave the way for future innovative strategies employing E. spinosus to protect cattle against endometritis. Full article
13 pages, 2545 KiB  
Article
Ability of Garlic and Ginger Oil to Reduce Salmonella in Post-Harvest Poultry
by Kelsy Robinson, Anna L. F. V. Assumpcao, Komala Arsi, Annie Donoghue and Palmy R. R. Jesudhasan
Animals 2022, 12(21), 2974; https://doi.org/10.3390/ani12212974 - 29 Oct 2022
Cited by 2 | Viewed by 1926
Abstract
Approximately 1.35 million human salmonellosis cases are reported in the United States every year, resulting in over 26,000 hospitalizations and 400 deaths. Consumption of contaminated poultry products is one of the leading causes of human salmonellosis. Poultry meat becomes contaminated when feces from [...] Read more.
Approximately 1.35 million human salmonellosis cases are reported in the United States every year, resulting in over 26,000 hospitalizations and 400 deaths. Consumption of contaminated poultry products is one of the leading causes of human salmonellosis. Poultry meat becomes contaminated when feces from an infected bird comes into contact with the carcass during processing. Additional carcasses can then become cross-contaminated along the processing line. While chemicals such as peracetic acid are currently used to kill microbes such as Salmonella, consumers are increasingly calling for more natural alternatives. Our objective for this study was to determine the ability of the phytochemicals garlic and ginger oil to reduce Salmonella prevalence in the processing environment. In a simulated scalding tank environment, dipping contaminated chicken skin samples in a solution containing both garlic and ginger oil reduced Salmonella by up to 2 log CFU. Furthermore, the oils prevented Salmonella growth in the tank solution. The mechanism of action of garlic and ginger was evaluated using the sub-inhibitory concentration of each oil individually. While both were found to decrease autoinducer-2 (AI-2) levels, no effect was seen on expression of 10 genes involved in Salmonella virulence and survival. In total, this work demonstrates the potential of garlic and ginger to reduce Salmonella prevalence in the post-harvest environment. However, more work remains to be done to understand the mechanism of action. Full article
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16 pages, 8475 KiB  
Article
Andrographolide and Deoxyandrographolide Inhibit Protease and IFN-Antagonist Activities of Foot-and-Mouth Disease Virus 3Cpro
by Sirin Theerawatanasirikul, Varanya Lueangaramkul, Nattarat Thangthamniyom, Penpitcha Chankeeree, Ploypailin Semkum and Porntippa Lekcharoensuk
Animals 2022, 12(15), 1995; https://doi.org/10.3390/ani12151995 - 07 Aug 2022
Cited by 5 | Viewed by 1889
Abstract
Foot-and mouth-disease (FMD) caused by the FMD virus (FMDV) is highly contagious and negatively affects livestock worldwide. The control of the disease requires a combination of measures, including vaccination; however, there is no specific treatment available. Several studies have shown that plant-derived products [...] Read more.
Foot-and mouth-disease (FMD) caused by the FMD virus (FMDV) is highly contagious and negatively affects livestock worldwide. The control of the disease requires a combination of measures, including vaccination; however, there is no specific treatment available. Several studies have shown that plant-derived products with antiviral properties were effective on viral diseases. Herein, antiviral activities of andrographolide (AGL), deoxyandrographolide (DAG), and neoandrographolide (NEO) against FMDV serotype A were investigated using an in vitro cell-based assay. The results showed that AGL and DAG inhibited FMDV in BHK-21 cells. The inhibitory effects of AGL and DAG were evaluated by RT-qPCR and exhibited EC50 values of 52.18 ± 0.01 µM (SI = 2.23) and 36.47 ± 0.07 µM (SI = 9.22), respectively. The intracellular protease assay revealed that AGL and DAG inhibited FMDV 3Cpro with IC50 of 67.43 ± 0.81 and 25.58 ± 1.41 µM, respectively. Additionally, AGL and DAG significantly interfered with interferon (IFN) antagonist activity of the 3Cpro by derepressing interferon-stimulating gene (ISGs) expression. The molecular docking confirmed that the andrographolides preferentially interacted with the 3Cpro active site. However, NEO had no antiviral effect in any of the assays. Conclusively, AGL and DAG inhibited FMDV serotype A by interacting with the 3Cpro and hindered its protease and IFN antagonist activities. Full article
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12 pages, 696 KiB  
Article
Antibacterial Potential of Caesalpinia coriaria (Jacq) Willd Fruit against Aeromonas spp. of Aquaculture Importance
by Lenin Rangel-López, Nallely Rivero-Perez, Benjamín Valladares-Carranza, Agustín Olmedo-Juárez, Lucía Delgadillo-Ruiz, Vicente Vega-Sánchez, Sawako Hori-Oshima, Mohamed A. Nassan, Gaber El-Saber Batiha and Adrian Zaragoza-Bastida
Animals 2022, 12(4), 511; https://doi.org/10.3390/ani12040511 - 18 Feb 2022
Cited by 8 | Viewed by 2263
Abstract
Aquaculture is an important source of food and livelihood for hundreds of millions of people around the world, however, aquaculture systems are affected by different factors, among them the appearance of resistant or multiresistant bacteria to antimicrobials. The secondary metabolites of plants have [...] Read more.
Aquaculture is an important source of food and livelihood for hundreds of millions of people around the world, however, aquaculture systems are affected by different factors, among them the appearance of resistant or multiresistant bacteria to antimicrobials. The secondary metabolites of plants have been proposed as alternatives for the treatment of these bacteria. The aim of the present study was to determine the antibacterial activity of Caesalpinia coriaria fruit hydroalcoholic extract and gallic acid over Aeromonas hydrophila, Aeromonas veronii,  and Aeromonas dhakensis to identify new molecules for the treatment of diseases caused by Aeromonas spp. The C. coriaria fruit hydroalcoholic extract (HECc) was obtained by hydroalcoholic maceration and subjected to bipartition with ethyl acetate and water to obtain an aqueous fraction (Ac-FrCc) and an organic fraction (Ac-FrEtCc); gallic acid was purchased commercially. The Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), MBC/MIC ratio, and cytotoxicity of HECc, its fractions, and gallic acid were determined. The results indicate that HECc fractions (Ac-FrCc and Ac-FrEtCc) and gallic acid have bactericidal activity against A. hydrophila and A. dhakensis, but only gallic acid showed bactericidal activity against A. veronii. The HECc and Ac-FrCc showed no toxicity, Ac-FrEtCc showed low toxicity, and gallic acid showed medium toxicity. The HECc, Ac-FrCc, and Ac-FrEtCc may be alternatives for the treatment of diseases caused by the genus Aeromonas, however, in vivo assays are necessary to corroborate these results. Full article
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11 pages, 1513 KiB  
Article
Efficacy of a Synergistic Blend of Organic Acids and ß-1,4 Mannobiose on Cecal Salmonella Counts and Growth Performance in Salmonella Challenged Broiler Chickens: A Meta-Analysis
by Sandra J. A. van Kuijk and Yanming Han
Animals 2021, 11(10), 2988; https://doi.org/10.3390/ani11102988 - 17 Oct 2021
Cited by 1 | Viewed by 1729
Abstract
This study aimed at investigating the effect of a functional synergistic feed additive blend, containing organic acids and ß-1,4 mannobiose, on cecal Salmonella counts and growth performance of broiler chickens. A meta-analysis combining 13 individual studies, executed in Salmonella-challenged broilers comparing a [...] Read more.
This study aimed at investigating the effect of a functional synergistic feed additive blend, containing organic acids and ß-1,4 mannobiose, on cecal Salmonella counts and growth performance of broiler chickens. A meta-analysis combining 13 individual studies, executed in Salmonella-challenged broilers comparing a control diet with and without the synergistic blend, was performed. Cecal Salmonella colonies and overall growth performance were measured. Raw data from all studies were combined and analyzed using PROC MIXED in SAS, taking the within and between-study variation into account. In the first 14 days post-inoculation (DPI), cecal Salmonella was reduced by 0.429 log CFU/g (p = 0.011, n = 10 comparisons from five studies) when feeding the synergistic blend compared to the control group. During 15–34 DPI, the overall means were not different between treatments (0.069 log CFU/g; p = 0.519, n = 12 comparisons from eight studies). The feed conversion ratio was improved when feeding the synergistic blend compared to the control diet (1.474 vs. 1.482, respectively; p = 0.002). In conclusion, feeding a synergistic blend, containing organic acids and ß-1,4 mannobiose amongst other ingredients, reduced cecal Salmonella counts during the first 14 DPI and improved growth performance of Salmonella challenged broilers compared to a control diet. Full article
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11 pages, 268 KiB  
Article
Phenotypic and Molecular Patterns of Resistance among Campylobacter coli and Campylobacter jejuni Isolates, from Pig Farms
by Dimitrios Papadopoulos, Evanthia Petridou, Konstantinos Papageorgiou, Ioannis A. Giantsis, Georgios Delis, Vangelis Economou, Ilias Frydas, Georgios Papadopoulos, Maria Hatzistylianou and Spyridon K. Kritas
Animals 2021, 11(8), 2394; https://doi.org/10.3390/ani11082394 - 13 Aug 2021
Cited by 6 | Viewed by 2695
Abstract
The purpose of this research was to characterize the antibiotic resistance patterns of Campylobacter spp. isolated from commercial farrow to finish farms in Greece, and analyze the relevant molecular resistance mechanisms among the resistant Campylobacter isolates. Susceptibility testing to five different classes of [...] Read more.
The purpose of this research was to characterize the antibiotic resistance patterns of Campylobacter spp. isolated from commercial farrow to finish farms in Greece, and analyze the relevant molecular resistance mechanisms among the resistant Campylobacter isolates. Susceptibility testing to five different classes of antibiotics was performed in 100 C. coli and 100 C. jejuni, previously isolated and identified. All isolates were found susceptible to meropenem. Very high rates of resistance were recorded for tetracyclines (84.5%), medium rates of resistance were recorded regarding quinolones (23%), and low and very low rates of resistance were identified for macrolides such as erythromycin and aminoglycosides (12% and 4%, respectively). Only 12.5% of the Campylobacter isolates displayed MDR. Regarding the molecular mechanisms of resistance, all ciprofloxacin resistant isolates hosted the mutant type Thr-86-Ile region of the quinolone resistance-determining region (QRDR) of the gyrA gene. In all erythromycin resistant isolates, the transitional mutations A2075G and A2074C in the 23S rRNA gene were only amplified. Molecular screening of tetracycline resistance genes indicated that the vast majority of Campylobacter isolates (92.3%) were positive for the tet(O) gene. In summary, these findings and especially the very high and medium rates of resistance for tetracyclines and fluroquinolones, respectively recommend that a continuous monitoring of Campylobacter isolates susceptibility in combination with the proper use of antimicrobials in livestock production is of great importance for public health. Full article

Review

Jump to: Research

15 pages, 912 KiB  
Review
Oxidized β-Carotene Is a Novel Phytochemical Immune Modulator That Supports Animal Health and Performance for Antibiotic-Free Production
by William W. Riley, James G. Nickerson, Trevor J. Mogg and Graham W. Burton
Animals 2023, 13(2), 289; https://doi.org/10.3390/ani13020289 - 14 Jan 2023
Cited by 3 | Viewed by 1934
Abstract
Oxidized β-carotene (OxBC), a phytochemical that occurs naturally in plants, is formed by the spontaneous reaction of β-carotene with ambient oxygen. Synthetic OxBC, obtained by full oxidation of β-carotene with air, shows considerable promise as an in-feed antimicrobial alternative additive that enhances health [...] Read more.
Oxidized β-carotene (OxBC), a phytochemical that occurs naturally in plants, is formed by the spontaneous reaction of β-carotene with ambient oxygen. Synthetic OxBC, obtained by full oxidation of β-carotene with air, shows considerable promise as an in-feed antimicrobial alternative additive that enhances health and performance in livestock. OxBC is predominantly composed of β-carotene-oxygen copolymers that have beneficial immune-modulating effects that occur within the innate immune system by priming it to face microbial challenges and by mitigating the inflammatory response. OxBC does not have any direct anti-bacterial activity. Further, unlike traditional immune stimulants, OxBC modulates but does not stimulate and utilize the animal’s energy stores unless directly stress-challenged. These immune effects occur by mechanisms distinct from the provitamin A or antioxidant pathways commonly proposed as explanations for β-carotene’s actions. Trials in poultry, swine, and dairy cows with low parts-per-million in-feed OxBC supplementation have shown performance benefits over and above those of feeds containing regular vitamin and mineral premixes. Through its ability to enhance immune function, health, and performance, OxBC has demonstrated utility not only as a viable alternative to in-feed antimicrobials but also in its ability to provide tangible health and performance benefits in applications where antimicrobial usage is precluded. Full article
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71 pages, 1391 KiB  
Review
Review on Preventive Measures to Reduce Post-Weaning Diarrhoea in Piglets
by Nuria Canibe, Ole Højberg, Hanne Kongsted, Darya Vodolazska, Charlotte Lauridsen, Tina Skau Nielsen and Anna A. Schönherz
Animals 2022, 12(19), 2585; https://doi.org/10.3390/ani12192585 - 27 Sep 2022
Cited by 22 | Viewed by 5188
Abstract
In many countries, medical levels of zinc (typically as zinc oxide) are added to piglet diets in the first two weeks post-weaning to prevent the development of post-weaning diarrhoea (PWD). However, high levels of zinc constitute an environmental polluting agent, and [...] Read more.
In many countries, medical levels of zinc (typically as zinc oxide) are added to piglet diets in the first two weeks post-weaning to prevent the development of post-weaning diarrhoea (PWD). However, high levels of zinc constitute an environmental polluting agent, and may contribute to the development and/or maintenance of antimicrobial resistance (AMR) among bacteria. Consequently, the EU banned administering medical levels of zinc in pig diets as of June 2022. However, this may result in an increased use of antibiotic therapeutics to combat PWD and thereby an increased risk of further AMR development. The search for alternative measures against PWD with a minimum use of antibiotics and in the absence of medical levels of zinc has therefore been intensified over recent years, and feed-related measures, including feed ingredients, feed additives, and feeding strategies, are being intensively investigated. Furthermore, management strategies have been developed and are undoubtedly relevant; however, these will not be addressed in this review. Here, feed measures (and vaccines) are addressed, these being probiotics, prebiotics, synbiotics, postbiotics, proteobiotics, plants and plant extracts (in particular essential oils and tannins), macroalgae (particularly macroalgae-derived polysaccharides), dietary fibre, antimicrobial peptides, specific amino acids, dietary fatty acids, milk replacers, milk components, creep feed, vaccines, bacteriophages, and single-domain antibodies (nanobodies). The list covers measures with a rather long history and others that require significant development before their eventual use can be extended. To assess the potential of feed-related measures in combating PWD, the literature reviewed here has focused on studies reporting parameters of PWD (i.e., faeces score and/or faeces dry matter content during the first two weeks post-weaning). Although the impact on PWD (or related parameters) of the investigated measures may often be inconsistent, many studies do report positive effects. However, several studies have shown that control pigs do not suffer from diarrhoea, making it difficult to evaluate the biological and practical relevance of these improvements. From the reviewed literature, it is not possible to rank the efficacy of the various measures, and the efficacy most probably depends on a range of factors related to animal genetics and health status, additive doses used, composition of the feed, etc. We conclude that a combination of various measures is probably most recommendable in most situations. However, in this respect, it should be considered that combining strategies may lead to additive (e.g., synbiotics), synergistic (e.g., plant materials), or antagonistic (e.g., algae compounds) effects, requiring detailed knowledge on the modes of action in order to design effective strategies. Full article
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