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      Vaccines as alternatives to antibiotics for food producing animals. Part 2: new approaches and potential solutions

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          Abstract

          Vaccines and other alternative products are central to the future success of animal agriculture because they can help minimize the need for antibiotics by preventing and controlling infectious diseases in animal populations. To assess scientific advancements related to alternatives to antibiotics and provide actionable strategies to support their development, the United States Department of Agriculture, with support from the World Organisation for Animal Health, organized the second International Symposium on Alternatives to Antibiotics. It focused on six key areas: vaccines; microbial-derived products; non-nutritive phytochemicals; immune-related products; chemicals, enzymes, and innovative drugs; and regulatory pathways to enable the development and licensure of alternatives to antibiotics. This article, the second part in a two-part series, highlights new approaches and potential solutions for the development of vaccines as alternatives to antibiotics in food producing animals; opportunities, challenges and needs for the development of such vaccines are discussed in the first part of this series. As discussed in part 1 of this manuscript, many current vaccines fall short of ideal vaccines in one or more respects. Promising breakthroughs to overcome these limitations include new biotechnology techniques, new oral vaccine approaches, novel adjuvants, new delivery strategies based on bacterial spores, and live recombinant vectors; they also include new vaccination strategies in-ovo, and strategies that simultaneously protect against multiple pathogens. However, translating this research into commercial vaccines that effectively reduce the need for antibiotics will require close collaboration among stakeholders, for instance through public–private partnerships. Targeted research and development investments and concerted efforts by all affected are needed to realize the potential of vaccines to improve animal health, safeguard agricultural productivity, and reduce antibiotic consumption and resulting resistance risks.

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          Intestinal epithelial cells: regulators of barrier function and immune homeostasis.

          The abundance of innate and adaptive immune cells that reside together with trillions of beneficial commensal microorganisms in the mammalian gastrointestinal tract requires barrier and regulatory mechanisms that conserve host-microbial interactions and tissue homeostasis. This homeostasis depends on the diverse functions of intestinal epithelial cells (IECs), which include the physical segregation of commensal bacteria and the integration of microbial signals. Hence, IECs are crucial mediators of intestinal homeostasis that enable the establishment of an immunological environment permissive to colonization by commensal bacteria. In this Review, we provide a comprehensive overview of how IECs maintain host-commensal microbial relationships and immune cell homeostasis in the intestine.
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            Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation

            Our intestinal microbiota harbours a diverse bacterial community required for our health, sustenance and well-being1,2. Intestinal colonisation begins at birth and climaxes with the acquisition of two dominant groups of strict anaerobic bacteria belonging to the Firmicutes and Bacteroidetes phyla2. Culture independent, genomic approaches have transformed our understanding of the role of the human microbiome in health and many diseases1. However, due to the prevailing perception that our indigenous bacteria are largely recalcitrant to culture, many of their functions and phenotypes remain unknown3. Here we describe a novel workflow based on targeted phenotypic culturing linked to large-scale whole genome sequencing, phylogenetic analysis and computational modeling that demonstrates that a substantial proportion of the intestinal bacteria are culturable. Applying this approach to healthy individuals, we isolated 137 bacterial species from characterised and candidate novel families, genera and species that were archived as pure cultures. Whole genome and metagenomic sequencing, combined with computational and phenotypic analysis, suggests that at least 50-60% of the bacterial genera from the intestinal microbiota of a healthy individual produce resilient spores, specialised for host-to-host transmission. Our approach unlocks the human intestinal microbiota for phenotypic analysis and reveals how a significant proportion of oxygen-sensitive intestinal bacteria can transmit between individuals, impacting microbiota heritability.
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              The use of bacterial spore formers as probiotics.

              The field of probiosis has emerged as a new science with applications in farming and aqaculture as alternatives to antibiotics as well as prophylactics in humans. Probiotics are being developed commercially for both human use, primarily as novel foods or dietary supplements, and in animal feeds for the prevention of gastrointestinal infections, with extensive use in the poultry and aquaculture industries. The impending ban of antibiotics in animal feed, the current concern over the spread of antibiotic resistance genes, the failure to identify new antibiotics and the inherent problems with developing new vaccines make a compelling case for developing alternative prophylactics. Among the large number of probiotic products in use today are bacterial spore formers, mostly of the genus Bacillus. Used primarily in their spore form, these products have been shown to prevent gastrointestinal disorders and the diversity of species used and their applications are astonishing. Understanding the nature of this probiotic effect is complicated, not only because of the complexities of understanding the microbial interactions that occur within the gastrointestinal tract (GIT), but also because Bacillus species are considered allochthonous microorganisms. This review summarizes the commercial applications of Bacillus probiotics. A case will be made that many Bacillus species should not be considered allochthonous microorganisms but, instead, ones that have a bimodal life cycle of growth and sporulation in the environment as well as within the GIT. Specific mechanisms for how Bacillus species can inhibit gastrointestinal infections will be covered, including immunomodulation and the synthesis of antimicrobials. Finally, the safety and licensing issues that affect the use of Bacillus species for commercial development will be summarized, together with evidence showing the growing need to evaluate the safety of individual Bacillus strains as well as species on a case by case by basis.
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                Author and article information

                Contributors
                khoelzer@pewtrusts.org
                bielke.1@osu.edu
                dblake@rvc.ac.uk
                Eric.Cox@UGent.be
                S.Cutting@rhul.ac.uk
                B.Devriendt@Ugent.be
                e.erlacher-vindel@oie.int
                Evy.Goossens@UGent.be
                karaca_kemal@elanco.com
                Stephane.lemiere@merial.com
                mmetzner@ripac-labor.de
                m.raicek@oie.int
                miquel.collell@merck.com
                nwong@pewtrusts.org
                Cyril.Gay@ars.usda.gov
                Filip.VanImmerseel@UGent.be
                Journal
                Vet Res
                Vet. Res
                Veterinary Research
                BioMed Central (London )
                0928-4249
                1297-9716
                31 July 2018
                31 July 2018
                2018
                : 49
                : 70
                Affiliations
                [1 ]ISNI 0000 0001 0694 6700, GRID grid.453225.7, The Pew Charitable Trusts, ; 901 E Street NW, Washington, DC, 20004 USA
                [2 ]ISNI 0000 0001 2285 7943, GRID grid.261331.4, Ohio Agriculture and Research Development Center, Animal Sciences, , Ohio State University, ; 202 Gerlaugh Hall, 1680 Madison Ave., Wooster, OH 44691 USA
                [3 ]ISNI 0000 0001 2161 2573, GRID grid.4464.2, Pathobiology and Population Sciences, Royal Veterinary College, , University of London, ; Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA UK
                [4 ]ISNI 0000 0001 2069 7798, GRID grid.5342.0, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, , Ghent University, ; Salsiburylaan 133, 9820 Merelbeke, Belgium
                [5 ]ISNI 0000 0001 2188 881X, GRID grid.4970.a, School of Biological Sciences, , Royal Holloway University of London, ; Egham, Surrey TW20 0EX UK
                [6 ]ISNI 0000 0001 2348 8166, GRID grid.475685.d, Science and New Technologies Department, , World Organisation for Animal Health (OIE), ; 12 Rue de Prony, 75017 Paris, France
                [7 ]ISNI 0000 0001 2069 7798, GRID grid.5342.0, Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, , Ghent University, ; Salsiburylaan 133, 9820 Merelbeke, Belgium
                [8 ]ISNI 0000 0004 0638 9782, GRID grid.414719.e, Elanco Animal Health, ; 2500 Innovation Way, Greenfield, IN USA
                [9 ]GRID grid.417924.d, Merial, ; 29 Avenue Tony Garnier, 69007 Lyon, France
                [10 ]RIPAC-LABOR GmbH, Am Mühlenberg 11, 14476 Potsdam, Germany
                [11 ]ISNI 0000 0001 2260 0793, GRID grid.417993.1, MSD, ; 2 Giralda Farms, Madison, NJ USA
                [12 ]ISNI 0000 0004 0478 6311, GRID grid.417548.b, Office of National Programs, Agricultural Research Service, , USDA, ; Sunnyside Ave, 5601 Beltsville, MD USA
                Author information
                http://orcid.org/0000-0003-2350-1062
                Article
                561
                10.1186/s13567-018-0561-7
                6066917
                30060759
                0a46b402-93ef-4929-aa59-d0b8d8aa8974
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 31 October 2017
                : 22 December 2017
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Veterinary medicine
                Veterinary medicine

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