Probiotics: A Modern Solution to Coccidiosis and Necrotic Enteritis
The decades-old practice of supplying food animals with sub-therapeutic doses of antibiotics to protect against infections and improve general health has recently been under scrutiny. These practices are perceived to lead to microbial resistance to the drugs in use, as well as consumer concerns regarding residues in food products. The relatively recent ban of sub-therapeutic doses of certain antibiotics as feed additives in the European Union led to a general decline in animal health (Castanon, 2007). This outcome, as well as the threat of a domestic ban, has led researchers to explore the next promising alternatives including probiotics, vaccines, and potential combinations of the two.
Although the primary function of the gastrointestinal tract is to digest and absorb nutrients, a well-balanced gut microbiota is crucial for optimal animal health and performance. The gastrointestinal tract also serves as a vital barrier preventing the entry of potentially harmful pathogens and other environmental antigens (Kogut and Swaggerty, 2012). As the gut microbiota begins to establish shortly after the chick hatches, the earlier the introduction of nonpathogenic microorganisms, the more effective is their establishment in the digestive tract (Timmerman et al., 2006, Torok et al., 2007). Also known as direct-fed microbials, probiotics are classified as live nonpathogenic microorganisms that are capable of maintaining a normal gut microbial population (Cox and Dalloul, 2015, Getachew, 2016). Probiotics help to maintain a healthy balance of microorganisms within the intestine, which is accomplished through multiple modes of action. Those mechanisms include competitive exclusion, pathogen antagonism, and stimulation of the immune system (Ohimain and Ofongo, 2012). The presence of probiotics reduces the colonization of pathogenic bacteria and attenuates enteric diseases, which ultimately result in enhanced performance of poultry (Kabir, 2009). Probiotics may provide a potential alternative to the prophylactic use of drugs in food animals due to their studied abilities to reduce enteric diseases in poultry (Eckert et al., 2010, Travers et al., 2011). Probiotics can be composed of one or many strains of microbial species, with the more common ones belonging to the genera Lactobacillus, Bifidobacterium, Enterococcus, Bacillus, and Pediococcus (Gaggia et al., 2010).
Coccidiosis and Mitigation Methods
Coccidiosis is endemic in the commercial broiler industry and inflicts devastating economic losses to poultry operations. Caused by development and reproduction of multiple species of the Eimeria protozoa, coccidiosis is estimated to cost the industry about US $3 billion annually worldwide (Dalloul and Lillehoj, 2006). Eimeria species are unlike other protozoan parasites where the primary target tissue is the intestinal epithelium, which results in considerable impairment of growth and feed utilization in poultry. The route of infection of these protozoa is through the consumption of fecal droppings of infected birds, as well as contaminated feed and litter (Chapman, 2014). The chicken is host to seven species of Eimeria, including the most common E. acervulina, E. maxima and E. tenella, each of which infects a specific area of the gut and invades the intestinal epithelial cells resulting in varying levels of tissue damage and morbidity (McDonald and Shirley, 2009). Depending on the species, magnitude, and site of infection, coccidiosis can result in a limited enteritis resulting in fluid loss and malabsorption of nutrients (typically due to E. acervulina and E. mitis), inflammation of the intestinal wall with pinpoint hemorrhages and sloughing of epithelia (as seen with E. brunetti and E. maxima), or complete villi destruction, leading to extensive hemorrhage and death (encountered with E. necatrix and E. tenella) (Chapman, 2014). The disruption of the intestinal epithelial layer naturally leads to the diminished ability of the intestine to absorb nutrients, resulting in reduced performance and higher susceptibility to other diseases, most notably necrotic enteritis caused by the bacterium Clostridium perfringens.
Currently, most producers rely on prophylactic measures such as anticoccidial drugs as well as vaccines to prevent coccidiosis in their flocks. Anticoccidial drugs, commonly referred to as coccidiostats, are administered in the feed at low doses during the grow-out period, with a withdrawal period prior to market weight and age. However, Eimeria species have developed resistance to both chemical and ionophore drugs over time (Stringfellow et al., 2011). These means of control are still considered effective only because parasite growth is suppressed sufficiently to allow natural immunity to develop (Blake and Tomley, 2014). Due to parasite resistance and consumer concerns regarding drug usage, the practice of live vaccines to control coccidiosis has greatly increased. Vaccines provide an alternative for disease protection, capable of limited efficacy as they induce specific protective immunity by exposing the chicken’s immune system to Eimeria antigens (Williams, 2002, Dalloul and Lillehoj, 2005, Stringfellow et al., 2011). Immunity is subsequently boosted and maintained by multiple re-infections caused by cycling of oocysts present in the litter due to shedding and ingestion (Williams, 2002). One drawback to live vaccines is that immunity to avian coccidia is strongly species-specific, therefore the bird will only develop immunity to the species of Eimeria present in the vaccine (Williams, 2002, Dalloul and Lillehoj, 2006). This specificity mandates that the vaccines have the species of Eimeria known to be prevalent in that area, which are more likely to cause an outbreak (Dalloul and Lillehoj, 2005). The necessary early administration of vaccines (typically during the first week of life) becomes a second disadvantage regarding live vaccines. Early exposure of the chick’s immune system to antigen results in immunity developing at a younger age, minimizing risk of exposure while the chick is unprotected. However, administration of live oocysts in a vaccine at a young age can result in a low level infection, which can cause an early reduction in growth and may increase the chick’s susceptibility to secondary infections, such as necrotic enteritis (Dalloul and Lillehoj, 2005, Stringfellow et al., 2011).
While the first drawback to use live vaccines is unavoidable, the chick may be able to combat the potential consequences of vaccine administration at a young age with a healthy intestinal tract and presence of normal microbiota (Stringfellow et al., 2011, Pender et al., 2016). Even though these methods are generally considered to be successful, due to the issues related to the use of anticoccidial drugs and vaccines, as well as the impending ban on animal feed additives, research has recently focused on more ‘natural’ means of controlling and managing coccidiosis. The use of an immunomodulator to manipulate the immune system is currently the most promising alternative. Probiotic supplementation is one option currently being explored as a means of reducing the amount and severity of enteric diseases in poultry and subsequent contamination of poultry products for human consumption. Probiotics have great potential to enhance host defenses and affect the digestive microbiota positively, while protecting against colonization by harmful bacteria and maintaining intestinal integrity (Eckert et al., 2010, Hume, 2011, Stringfellow et al., 2011, Ritzi et al., 2014, Pender et al., 2016). Further, probiotics (e.g. PoultryStar®) not only can afford the birds protection against a coccidiosis challenge, but they may also attenuate the negative consequences of early vaccine administration (Ritzi et al., unpublished data). The use of probiotics is based on the understanding that a well-balanced gut microbiota is crucial for optimal animal health and performance. Alterations in the microbial profile can influence all aspects of the gastrointestinal tract, including development, physiology, immunology, and resistance to enteric infections, through interactions of the microorganisms with the intestinal lining and lymphoid tissues.
Necrotic enteritis has reemerged as an important disease of poultry in recent years, and Clostridium perfringens is the etiological agent associated with this enteric disease (Opengart, 2008). The reduction in the use of sub-therapeutic doses of antimicrobials in poultry feeds has been attributed as one of the main causes of the increasing incidence of necrotic enteritis in commercial poultry. Mortality due to necrotic enteritis can be extremely high (1% daily mortality) resulting in significant production losses. Such high mortality rates are not the only culprit of economic losses due to necrotic enteritis, reduction in bird performance and feed efficiency also are extremely costly especially during subclinical cases of the disease. Further, birds that survive necrotic enteritis outbreaks usually have reduced abilities to digest and absorb nutrients due to extensive damage to the mucosal lining, and require longer time to fully recover. The reduction in bird performance is not only associated with impaired growth rate and feed conversion during production, but also with increased condemnation rates in broilers due to hepatitis at processing (Opengart, 2008). This enterotoxaemia of poultry is estimated to cost the global poultry industry over US $2 billion due to mortality, reduced performance, and secondary infections.
Clostridium perfringens is a naturally occurring Gram-positive bacterium in the intestines of warm blooded animals, and by itself is not a determining factor for disease development. Instead, pre-disposing factors that could lead to a favorable environment and an outgrowth of these bacteria are crucial to the onset and development of necrotic enteritis. Several different factors have been identified as potential pre-disposing factors including diets, immune status of the bird, intestinal physiology and stress, and coccidiosis (McReynolds et al., 2009, Timbermont et al., 2011, Paiva et al., 2013 and 2014, Moran, 2014). The latter seems to be a common theme among existing experimental models of necrotic enteritis, and Eimeria parasites are commonly encountered during field outbreaks. It is no surprise as both pathogens are ubiquitous in the environment particularly in commercial settings. As such, necrotic enteritis prevention can be associated with management practices, which include minimizing the effects of pre-disposing factors that contribute to disease development. Removing certain dietary ingredients such as fish meal and controlling coccidiosis have been effective in reducing incidences of necrotic enteritis (Cooper and Songer, 2009). As with coccidiosis, the use of probiotics (e.g. PoultryStar®) as feed or water additives has demonstrated positive impact in poultry (McReynolds et al., 2009, Layton et al., 2013, Tactacan et al., 2013, Caly et al., 2015).
The small intestine is the largest lymphoid organ as well as a vital component of the digestive system. The integrity of the digestive tract is essential for protecting the host against enteric diseases such as coccidiosis. With the ban of antibiotics as feed additives by the European Union and the threat of the ban being carried to the U.S., more consumer friendly and ‘natural’ alternatives need to be procured in the near future. The findings of various studies with probiotics, including PoultryStar, support the protective effects provided by probiotic administration, both in feed and water applications, against enteric pathogens. Supplementation of probiotics enhances performance in poultry and provides protection against several economically important diseases including coccidiosis and necrotic enteritis. Manipulation of intestinal microbiota through the use of probiotics promotes the development of the intestinal tract and its local immune system. Through numerous studies, the safety and efficacy of probiotic administration in challenge settings have been demonstrated. Such positive impact of probiotics included enhanced feed conversion and reduced damage to the intestinal epithelium. Further, certain aspects associated with live coccidiosis vaccination, such as delayed growth and early intestinal epithelial damage, were reduced with probiotic supplementation, resulting in healthier broiler chickens. This interaction between probiotics and coccidiosis vaccines seems encouraging, as some of our data support the theory that the two together afford better protection against infection by Eimeria species than the administration of either on its own. As such, additional larger scale studies would further investigate the relationship between the two, including different administration methods of the probiotic formulation. Deeper details on work in this area is evidently beyond this proceedings paper. However, the presentation and discussion of this topic at the 2016 World Nutrition Forum should provide an overview of existing research and an update on the state-of-the-art on using probiotics in the poultry industry, within the context of coccidiosis and necrotic enteritis.