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

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.

Passive immunisation, an old idea revisited: Basic principles and application to modern animal production systems

“…Also, hyperimmune SDP from pigs vaccinated against F4+ ETEC more efficiently reduced shedding of F4+ ETEC in an experimental model of PWD than SDP from non-immunised animals (Niewold et al, 2007). As methods are now in place to efficiently purify immunoglobulin from slaughterhouse pig plasma by very cost-efficient methods (Lihme et al, 2010) it would be attractive to use the purified immunoglobulin fraction itself instead of SDP, and the anti-bacterial effect in experimentally challenged weaning piglets of such a purified immunoglobulin fraction purified in bulk from slaughterhouse blood was demonstrated recently by us (Hedegaard et al, 2016). The slaughterhouse pig plasma was shown to contain 'natural' antibody activity against both E. coli and Salmonella enterica spp (Hedegaard et al, 2016).…”

“…Colostrum also contains leukocytes and antimicrobial proteins (such as Complement C3, lactoferrin, lactoperoxidase, and lysozyme) (Hernandez-Castellano et al, 2015;Smolenski et al, 2007). Colostral leukocytes are believed to participate in oro-gastric protection together with maternal immunoglobulins (Goldman, 1977;Morgan et al, 1984), and may enter circulation by intestinal absorption promoting neonatal cellular immunity (Liebler-Tenorio et al, 2002;Salmon et al, 2009;Tuboly and Bernath, 2002).…”

“…Intact, non-denatured IgG could also be found throughout the digestive system after oral administration of ovine IgG to rats (Balan et al, 2014). It should be noted that colostrum contains protease inhibitors, such as inter-alpha-trypsin inhibitor and alpha-1-antichymotrypsin (Danielsen et al, 2011;Hernandez-Castellano et al, 2015). Also, the pH in the stomach of weaned piglets is never below 2.5 (Snoeck et al, 2004), both of which contribute to sustain immunoglobulin stability upon oral administration…”

Mink (Neovison vison) kits with pre-weaning diarrhea have elevated serum amyloid A levels and intestinal pathomorphological similarities with New Neonatal Porcine Diarrhea Syndrome

“…The observed attachment of coccoid bacteria may be responsible for an enterotoxic effect causing a loss of balance of movements of ions and water leading to the vacuolization and swelling of the enterocytes. Interestingly, the attachment of enterococci and E. coli to enterocytes and the slight to moderate infiltrations of neutrophils irrespective of diarrheic status has recently been found in piglets suffering from New Neonatal Porcine Diarrhea Syndrome (NNPDS) [38][39][40], suggesting similarities in mechanisms between diarrhea in the pre-weaning period of mink kits and piglets. Elevated levels of SAA and adhesion of bacteria to the intestinal wall has been seen for segmented filamentous bacteria (SFB), which adhere to the enterocytes, inducing epithelial SAA production [41,42].…”

The Gut Microbiota composition of Feral and Tamworth Pigs determined using High-Throughput Culturomics and Metagenomics Reveals Compositional Variations When Compared to the Commercial Breeds

“…It has become clear in recent years, that the microbiome has a drastic impact on host health. Many current methods to study the swine microbiome, are based upon dietary intervention (Hedegaard, et al 2016: e0147373, Metzler-Zebeli, et al 2015: 8489). That is, a dietary substrate is introduced to the animal and an effect on microbiome composition, typically 16s rRNA analysis, is measured.…”