Non-antibiotic Strategies to Reduce Inflammation in Poultry

Published: August 26, 2021

By: Douglas R. Korver / Professor of Poultry Nutrition, Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB

Summary

Poultry hatch with an under-developed acquired immune system, and rely heavily on innate immunity. However, inflammation can divert nutrients and energy away from growth and production. Strategies to reduce the intensity and duration of inflammation, and transition towards the maturing acquired immune system can allow for efficient production while maintaining bird health. Antibiotic growth promotors (AGP) directly or indirectly reduced systemic inflammation caused by microbes within the digestive tract, thus maintaining efficient production. As the poultry industry moves away from the use of AGP, successful alternative strategies will also manage systemic inflammation. Although individual products may show promise in laboratory or controlled production settings, translation to the field has been less successful. A potential reason is that AGP provided a broad protection against performance-reducing organisms. Although individual replacements may be effective against a particular group of problem organisms, or under specific conditions, no single product has yet been an effective one-for-one replacement of AGP. Therefore, a combination of different product types, with different mechanisms, may be required to match the broad-based effectiveness of AGP. Additionally, the optimum combination of alternatives may vary from company to company, location to location, and season to season over time. The transition away from AGP has been successful in many places, including Canada, but has generally involved a methodical evaluation of various combinations of alternative products. By understanding the mechanisms of each alternative approach, and the specific challenges faced on each farm, a strategic approach can be used to effectively transition from AGP use.

Introduction

The immune system of poultry is typically divided into innate responses and adaptive responses, and reviews of the avian immune system can be found elsewhere (Korver, 2012; Kogut, et al., 2020). Briefly, the innate response includes non-specific mechanisms of exclusion such as the skin and mucosal surfaces of the digestive tract, lungs and other organ systems with exposure to the outside world. Thus, one of the primary means of immunological protection is the prevention the interaction of potential pathogens with the internal environment of the animal. Should a foreign organism gain contact with the internal environment through a break in the skin or disruption of the intestinal barrier, non-specific innate immune mechanisms at the site of infection (e.g. local inflammation, recruitment of phagocytic cells, etc.) and potentially, systemic physiological changes (e. g. systemic inflammation, fever, anorexia, cachexia, etc.) are activated. Thus, the innate immune response is an essential, but potentially costly means of host protection.

Unlike the innate response, the adaptive immune response works against specific target antigens (Kogut, et al., 2020). In order for a strong adaptive response to occur, a primary exposure to a pathogen must be recognized (in a general sense, as being “foreign”) by the innate immune system, and antigens presented to the cells of the adaptive response. Future exposure to the same antigen can then result in a rapid, specific response to counteract continued infection. This is the strategy employed in vaccination programs. Broiler chicks hatch with a limited adaptive immune response (Bar-Shira, et al., 2003; Bar-Shira and Friedman, 2005; Bar-Shira and Friedman, 2006; Friedman, et al., 2007), and as such rely heavily on innate immunity for the first part of life (Alkie, et al., 2019).

The adaptive immune response works in conjunction with the innate response. Foreign antigens are processed and presented by cells of the innate immune system to cells of the adaptive immune system (Sylte and Suarez, 2012; Chhabra, et al., 2015). The vaccination response requires an initial activation of the innate immune system (Schijns, et al., 2014), which comes at an energetic and nutritional cost associated with the initial involvement of innate immunity. Therefore, vaccination against specific diseases must be viewed in the context of the cost of the innate response on performance vs the likelihood of a particular disease being encountered by the flock.

General Strategies to Replace Antibiotic Growth Promotors

Antibiotics have used to increase chicken growth rates since 1940’s (Moore, et al., 1946; Castanon, 2007). Although a number of mechanisms have been proposed (Visek, 1978; Thomke and Elwinger, 1998; Dibner and Richards, 2005), it appears that ultimately, the growth promoting (i.e. allowing the birds to express a greater proportion of their genetic potential) effects are primarily mediated through a reduction in intestinal (Oh, et al., 2019) and systemic inflammation (Roura, et al., 1992; Niewold, 2007). Therefore, it is reasonable to conclude that successful strategies to replace AGP will also involve the direct or indirect reduction of inflammation through reducing the local and systemic effects of inflammation.

The removal of antibiotic growth promotors (AGP) increases the risk of subclinical and clinical bacterial infections that can result in the diversion of nutrients away from growth in support of the systemic inflammatory response (Broom and Kogut, 2018). The physiologic changes associated with systemic inflammation such as reduced feed intake, anorexia, cachexia, fever, etc. reduce the amount of nutrients available for growth (Iseri and Klasing, 2013a; Iseri and Klasing, 2013b; Iseri and Klasing, 2014).

The changes in metabolism and physiology associated with a continued activation of a systemic innate response will decrease the productivity of broilers. Therefore, a holistic approach to managing bird health while reducing or eliminating antibiotic growth promotors in broiler production should include:

Reduce exposure to challenges that will initiate systemic inflammation. Bacterial infections can reduce the growth and efficiency of broiler chickens (Remus, et al., 2014). In the context of AGP replacement strategies, this means reducing the immunological interaction between the host and potential pathogens. This can be done by reducing the prevalence of potential pathogens, maintaining a healthy barrier function of the gut, and using products that prevent proliferation and invasion of tissues by pathogenic bacteria. Even low-grade intestinal inflammation can lead to reduced performance (Dal Pont, et al., 2020). Ultimately, one of the main effects of AGP is to reduce these interactions, and decrease systemic inflammation.
Rapid resolution of systemic inflammation. The innate response is essential for the bird’s well-being, but excessive activation, or extended activation will reduce performance. The more quickly the innate response can be resolved, the lower the impact on performance. Alternatively, reducing the systemic effects of inflammation while maintaining a strong local response can achieve the same end goal (Korver and Klasing, 1997; Korver, et al., 1997).
Rapid transition from innate to adaptive immunity. The innate response is essential for the initial recognition of a pathogen, but a transition from innate to an effective adaptive response will decrease the overall impact of immune activation (Broom and Kogut, 2018).

Evaluating Replacements for Antibiotic Growth Promotors

When evaluating the potential of an individual product or multi-product strategy to replace AGP, it is essential that the supporting research be conducted appropriately. The simplest, but incorrect approach to evaluating a potential AGP replacement is to run an experiment in which two diets are fed: a positive control containing an AGP, and a test diet containing the test product, but no AGP. A lack of difference in performance is interpreted as evidence that the product can successfully replace AGP. However, in low-challenge research environments, the inclusion or exclusion of an AGP may have no effect on broiler performance, since in the absence of a bacterial challenge, there is no opportunity for the AGP to act. In very clean environments, there will be little inflammation, even in the absence of AGP (Roura, et al., 1992). Therefore, it cannot be concluded whether the replacement would have an effect in the case of a challenge. In field research, however, it may be impractical to include a true negative control, since commercial producers are not likely to accept the potential of substantial economic losses inherent in a true negative control treatment. In such cases, it may only be possible to include a positive control, and a test product for which there is already a strong indication of effectiveness from smaller-scale studies. To increase the confidence in the outcomes of field studies like this, all treatments should be included within a statistical block (i.e. a production unit -- within individual barns, or across barns at a single location), and the number of blocks should be replicated as often as is feasible, either across locations, or across time.

In addition to sound experimental design principles, the following criteria are essential for controlled AGP-replacement research studies:

A positive control treatment containing a relevant AGP. Depending on the product(s) being tested, and the target disease challenge being study, the PC may or may not have a coccidiostat included.
A negative control treatment without AGP, and without any test product. In order to be able to draw valid conclusions about efficacy, there must be a reduction in performance in this group relative to the PC. This provides evidence that there is a challenge in the experimental environment, and that the inclusion of an AGP mitigates this challenge. In the absence of reduced performance in the negative control group, it is impossible to evaluate the effects of a test product, because in this situation the AGP had no effect on performance. Often this approach includes the use of a clinical or sub-clinical challenge model to all treatment groups, including the positive control and test groups.
One or more experimental treatments based on the negative control diet, but containing the product(s) of interest. As noted above, it is necessary for the positive control group to have superior performance to the negative control group. If performance of the test group is statistically identical to that of the negative control, it can be concluded that the product has no effect. If the test group has performance greater than the negative control group, but statistically similar to the positive control, it can be concluded that, under the conditions of the experiment, the test product was effective as an AGP. If performance of the test group is intermediate to the positive and negative controls, it can be concluded that, under the experimental conditions, the product could be a partial replacement for AGP, but additional strategies may be needed to obtain equivalent protection as provided by AGP.

Although results may show promise in small-scale, well-controlled experiments, it is necessary to proceed with caution before declaring a product or combination to be an effective replacement for AGP. The results obtained in highly-controlled research facilities may translate with limited success to commercial conditions.

Specific Approaches to Replacing Antibiotic Growth Promotors

Although many potential AGP replacements have been proposed, experience has shown that success is not as simple as a one-for-one replacement of AGP with another product.

Additionally, with a narrower specificity than AGP, it is important to identify the specific types of challenges that are likely at particular times of life, and strategically apply products intended to address those particular issues. So, rather than removing AGP from each dietary phase and replacing a single product or combination of products throughout the life of the bird, it may be necessary to transition from one product or group of products to another over time as the type of challenge changes.

A large number of products or compounds have been proposed as alternatives to antibiotics. It is not the author’s intention to review all proposed alternatives, but rather to give a broad overview of products (Table 1). The efficacy of individual approaches or combinations of approaches need to be evaluated in the context of the published literature, as well as experience in the field. Immunomodulatory nutrients may also play a part in the overall strategy of a move away from growth promoting antibiotics, since they can influence the systemic responses to inflammatory challenges (Korver, 1997; Korver and Klasing, 1997; Korver, et al., 1997; Wils-Plotz, et al., 2013; Wils-Plotz and Klasing, 2015; Wils-Plotz and Klasing, 2017), but are reviewed elsewhere (Klasing, 2007; Adedokun and Olojede, 2019; Swaggerty, et al., 2019).

Table 1. Examples of products or strategies showing promise as AGP replacements.

ANCC2020 - Non-antibiotic Strategies to Reduce Inflammation in Poultry - Image 1

Click here to enlarge the image

The path forward to consistent success in AGP-free broiler chicken production will likely depend on a combination of products with differing mechanisms of action. Making this more difficult is the likelihood that different geographical regions, or different growing facilities within a region may need slightly different combinations or approaches. Although individual products may show promise in laboratory or controlled production settings, translation to the field has been less successful. A potential reason is that AGP provided a broad protection against performance-reducing organisms. Although individual replacements may be effective against a particular group of problem organisms, or under specific conditions, no single product has yet been an effective on-for-one replacement of AGP. Therefore, a combination of different product types, with different mechanisms, may be required to match the broad-based effectiveness of AGP.

It is important to note that excellent animal care and husbandry will become even more important. AGP replacements will likely be less forgiving than AGP towards poor management or substandard environments. Novel strategies will be part of an overall program to maintain optimum health, since even AGP cannot overcome every possible disease challenge.

The broiler industry worldwide is transitioning, or has already transitioned to AGP-free production, with varying degrees of success. The evaluation of novel AGP replacement products must follow sound scientific principles, with robust experimental design and data analysis. Transition to commercial use should follow only after a demonstration of effectiveness under field conditions. Individual producers should be aware of the specific issues associated with the age of the bird, and their geographical location, and choose strategies to address those issues. Development of a farm-specific approach will likely take trial and error, and will likely take several years to develop. However, continual progress can be made with identification of candidate products, robust testing under controlled conditions, strategic testing under field conditions, and continual evaluation and improvements as new products and combinations become available.

Published in the proceedings of the Animal Nutrition Conference of Canada 2020. For information on the event, past and future editions, check out https://animalnutritionconference.ca/.

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