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      Natural Pig Plasma Immunoglobulins Have Anti-Bacterial Effects: Potential for Use as Feed Supplement for Treatment of Intestinal Infections in Pigs

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          Abstract

          There is an increasing demand for non-antibiotics solutions to control infectious disease in intensive pig production. Here, one such alternative, namely pig antibodies purified from slaughterhouse blood was investigated in order to elucidate its potential usability to control post-weaning diarrhoea (PWD), which is one of the top indications for antibiotics usage in the pig production. A very cost-efficient and rapid one-step expanded bed adsorption (EBA) chromatography procedure was used to purify pig immunoglobulin G from slaughterhouse pig plasma (more than 100 litres), resulting in >85% pure pig IgG (ppIgG). The ppIgG thus comprised natural pig immunoglobulins and was subsequently shown to contain activity towards four pig-relevant bacterial strains (three different types of Escherichia coli and one type of Salmonella enterica) but not towards a fish pathogen ( Yersinia ruckeri), and was demonstrated to inhibit the binding of the four pig relevant bacteria to a pig intestinal cell line (IPEC-J2). Finally it was demonstrated in an in vivo weaning piglet model for intestinal colonization with an E. coli F4+ challenge strain that ppIgG given in the feed significantly reduced shedding of the challenge strain, reduced the proportion of the bacterial family Enterobacteriaceae, increased the proportion of families Enterococcoceae and Streptococcaceae and generally increased ileal microbiota diversity. Conclusively, our data support the idea that natural IgG directly purified from pig plasma and given as a feed supplement can be used in modern swine production as an efficient and cost-effective means for reducing both occurrence of PWD and antibiotics usage and with a potential for the prevention and treatment of other intestinal infectious diseases even if the causative agent might not be known.

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          Most cited references25

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          Perspectives on Immunoglobulins in Colostrum and Milk

          Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk.
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            The mucosal immune system and its integration with the mammary glands.

            Mucosal immunity reduces the need for elimination of penetrating exogenous antigens by proinflammatory systemic immunity. The adult gut mucosa contains some 80% of the body's activated B cells-differentiated to plasmablasts and plasma cells (PCs). Most mucosal PCs produce dimeric immunoglobulin A (IgA), which, along with pentameric immunoglobulin M (IgM), can be exported by secretory epithelia expressing the polymeric immunoglobulin receptor. Immune exclusion of antigens is performed mainly by secretory IgA in cooperation with innate defenses, but, in newborns and in IgA deficiency, secretory IgM is important. In the gut, induction and regulation of mucosal immunity occurs primarily in gut-associated lymphoid tissue-particularly the Peyer's patches-and also in mesenteric lymph nodes. Terminal differentiation to PCs is accomplished in the lamina propria to which the activated memory/effector T and B cells home. Lactating mammary glands are part of the secretory immune system, and IgA antibodies in breast milk reflect antigenic stimulation of gut-associated lymphoid tissue and nasopharynx-associated lymphoid tissue such as the tonsils. Breast-milk antibodies are thus highly targeted against infectious agents and other exogenous antigens in the mother's environment, which are those likely to be encountered by the infant. Therefore breast-feeding represents an ingenious immunologic integration of mother and child. Copyright 2010 Mosby, Inc. All rights reserved.
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              Enteric infection meets intestinal function: how bacterial pathogens cause diarrhoea.

              Infectious diarrhoea is a significant contributor to morbidity and mortality worldwide. In bacterium-induced diarrhoea, rapid loss of fluids and electrolytes results from inhibition of the normal absorptive function of the intestine as well as the activation of secretory processes. Advances in the past 10 years in the fields of gastrointestinal physiology, innate immunity and enteric bacterial virulence mechanisms highlight the multifactorial nature of infectious diarrhoea. This review explores the various mechanisms that contribute to loss of fluids and electrolytes following bacterial infections, and attempts to link these events to specific virulence factors and toxins.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 January 2016
                2016
                : 11
                : 1
                : e0147373
                Affiliations
                [1 ]National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark
                [2 ]Upfront Chromatography A/S, Copenhagen, Denmark
                Indian Institute of Science, INDIA
                Author notes

                Competing Interests: Marie Bendix Hansen, Bodil Kjær Lindved and Allan Lihme (all employed at Upfront Chromatography A/S) have financial interest in the study. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: CJH MLS MB PH. Performed the experiments: CJH MLS. Analyzed the data: CJH MLS PH. Contributed reagents/materials/analysis tools: MLS MBH BKL AL. Wrote the paper: CJH MLS PH. Obtained approval from the Danish Animal Experiments Inspectorate under the Ministry of Justice: MLS MB.

                Article
                PONE-D-15-36707
                10.1371/journal.pone.0147373
                4744083
                26824607
                f1991889-af67-49c7-9733-f569953cc90c
                © 2016 Hedegaard et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 August 2015
                : 15 December 2015
                Page count
                Figures: 4, Tables: 1, Pages: 14
                Funding
                The project was supported by Green Development and Demonstration Programme (Ministry of Food, Agriculture and Fisheries, The Danish AgriFish Agency, Journal number: 34009-12-0471). The funder provided support in the form of salaries for the author CJH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The commercial affiliation did provide purified plasma IgG for this study.
                Categories
                Research Article
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Antibodies
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Antibodies
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Biology and Life Sciences
                Biochemistry
                Proteins
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                Biology and Life Sciences
                Agriculture
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                Swine
                Biology and Life Sciences
                Organisms
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                Vertebrates
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                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Escherichia Coli Infections
                Research and Analysis Methods
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                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Medicine and Health Sciences
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                Custom metadata
                All relevant data are within the paper. Data regarding the microbiome have been uploaded to Genbank database: http://www.ncbi.nlm.nih.gov/sra/SRP066524.

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