TRIENNIAL GROWTH SYMPOSIUM: A review of science leading to host-targeted antibody strategies for preventing growth depression due to microbial colonization1,2

Abstract

In this review, the science used to develop host-targeted therapies for improving animal growth and feed efficiency is presented. In contrast to targeting the microbiota of the host, endogenous host proteins are targeted to regulate an overactive inflammatory response in the host. Activation of the immune/inflammatory systems of an animal is costly in terms of growth and feed efficiency. For example, reduced rates of BW gain and poorer feed efficiency in vaccinated animals compared with nonvaccinated animals have been well documented. Also, the growth rate and feed efficiency of animals colonized by microorganisms is only 80 to 90% of their germ-free counterparts. Further evidence of a cost associated with immune activation is that strategies that enhance the immune capability of an animal can reduce animal growth and feed efficiency. Research now indicates that the growth-promoting effects of antibiotics are indirect, and more likely the result of reduced immune activation due to decreased microbial exposure. Studies of mechanisms by which immune/inflammatory activation reduces animal growth and feed efficiency have shown that cytokines of the acute inflammatory response (i.e., IL-1 and tumor necrosis factor α) are key triggers for host muscle wasting. Cytokine-induced muscle wasting is linked to PG signaling pathways, and it has been proposed that regulation of the PG signaling pathways provide host targets for preventing an overreactive or unwarranted inflammatory event. Intestinal secretory phospholipase A(2) (sPLA(2)) has been found to be a useful and accessible (i.e., found in the intestinal lumen) host target for the regulation of an overreactive inflammatory response to conventional environments. This review presents the science and strategy for the regulation of intestinal sPLA(2) using orally administered egg yolk antibody against the enzyme. Clinically healthy animals fed egg antibodies to sPLA(2) had improved growth and feed efficiency. Literature presented indicates that use of host-targeted strategies for regulating the overexpression of inflammatory processes in an animal may provide new mechanisms to improve animal growth and feed efficiency.

Biology of the Gastrointestinal Tract in Poultry

“…There is moderate expression of the receptor for ghrelin, growth hormone secretagoguereceptor (GHS-R), in the crop of Japanese quail (Kitazwa et al, 2009). Moreover, crop emptying is also influenced by the brain; it is depressed by intracerebral injections of gastrin , glucagon-like peptide-1, neuromedins B, C or bombesin (Tachibana et al, 2003;2010). It is not clear whether these effects are mediated through the gastrin releasing peptide or the bombesin receptors.…”

“…The growth rate of GF poultry is 10-20% greater than that of conventional poultry. This is probably due to the lack of adverse effects of microbial colonisation of the gastro-intestinal tract and/or activation of gastro-intestinal immune/inflammatory responses (reviewed Cook, 2010).…”

Egg Yolk Antibodies for Passive Immunity

“…To this end, the use of IgY targeting specific molecules involved in inflammation and animal growth has been described. Antibodies directed against the gut neuropeptides cholecystokinin and neuropeptide Y, believed to be involved in regulating appetite, as well as the enzyme PLA 2 , which plays a role in the production of the inflammatory mediators prostaglandins and leukotrienes, have both been shown to improve growth and feed efficiency when fed to chickens (reviewed in Cook 2004Cook , 2010. Similarly, Mahdavi et al (2010) found that feeding yolk powder containing IgY against E. coli O78:K80 to chickens improved intestinal health and feed conversion ratio, and enhanced intestinal responses upon oral challenge.…”

Inclusion of anti-phospholipase A2 antibody to backgrounding diets on performance, feed efficiency, in vitro fermentation, and the acute-phase response of growing beef calves1

“…Upon activation of the immune system and the APR, an organism diverts nutrients away from growth and development, redirecting it into defense processes (Johnson, 1997) followed by immediate decrease in feed intake, wasting of skeletal muscle, increased lipolysis and production of acute-phase proteins (APP) by the liver, plasma mineral alterations, fever, and changes in behavior (Johnson, 1997;Cook, 2011;Cooke and Bohnert, 2011). One theory hypothesizes that pathogens and lipopolysaccharides (LPS) translocate into the bloodstream through activation of secretory phospholipase A 2 (sPLA 2 ) in the intestinal lumen, and once in the bloodstream, LPS stimulates leukocyte production of proinflammatory cytokines with further activation of the APR, leading to physiological responses that have direct effects on animal performance (Cook, 2011). Feed efficiency (FE) and growth was improved in a series of studies with poultry, swine, and fish using an egg-derived antibody against sPLA 2 (anti-phospholipase A 2 antibody [aPLA 2 ]) as a feed additive (Yang et al, 2003;Cook, 2004Cook, , 2011Barry and Yang, 2008).…”

“…One theory hypothesizes that pathogens and lipopolysaccharides (LPS) translocate into the bloodstream through activation of secretory phospholipase A 2 (sPLA 2 ) in the intestinal lumen, and once in the bloodstream, LPS stimulates leukocyte production of proinflammatory cytokines with further activation of the APR, leading to physiological responses that have direct effects on animal performance (Cook, 2011). Feed efficiency (FE) and growth was improved in a series of studies with poultry, swine, and fish using an egg-derived antibody against sPLA 2 (anti-phospholipase A 2 antibody [aPLA 2 ]) as a feed additive (Yang et al, 2003;Cook, 2004Cook, , 2011Barry and Yang, 2008). However, the use of aPLA 2 as a feed additive for cattle diets has not been reported.…”