The strategic importance of feed additives on animal health and performance in the post-antibiotic world

Introduction

Animal husbandry, the agricultural practice of breeding and raising livestock, is a major food-producing industry worldwide. The increasing global demand for animal protein results in rapidly growing animal production as well as the growth of animal feed and the feed additive market. The feed additives have played a significant role in the sustainability of the livestock industry. There are four major drivers for the growth of the animal feed additive market including: 1) increasing consumption of meat and dairy products, 2) antibiotics bans or restrictions, 3) favourable regulatory norms (e.g., carbon neutral), and 4) increasing livestock disease outbreaks. Antibiotics are widely used in modern livestock production as growth promoters primarily due to prevention of livestock diseases. According to the Canadian Animal Health Institute, Canadian livestock consumed more than 1.5 million kilograms of antibiotics in 2014 (Canadian Antimicrobial Resistance Surveillance System Report 2016). Global consumption of antibiotics from food animal production was estimated at 63,151 tons in 2010 and is predicted to rise dramatically by 67% by 2030 (Van Boeckel et al., 2015). This practice has been linked to the spread of antimicrobialresistant pathogens in both livestock and humans, posing a significant public health threat. Regulatory actions to reduce or eliminate the use of antibiotics in livestock feeds are being considered in Canada and worldwide. The European Union banned the use of antibiotic growth promoters in animal food production in 2006. The U.S. Food and Drug Administration placed restrictions on antibiotic use in animal production in December 2016 and Health Canada prohibited the use of antibiotic growth promoter in animal feeds starting in December 2017; more countries are expected to follow. However, withdrawal of antibiotics from feeds can result in several challenges including compromised gut health and a rise in gut diseases (Omonijo et al., 2018). Consumers want a food system that assures their food is safe, affordable, healthy, and sustainable causing more and more companies to commit to reducing their carbon footprint. Therefore, strategic feed additive solutions to the development of antibiotic alternatives, mycotoxin mitigation, early nutrition, targeting the quality and safety of animal products, cost reduction, better efficiency, and less environment impact for sustainable livestock production are urgently needed as the livestock industry complies with these new regulations.

Alternatives to Antibiotics: Challenges and Solutions for Livestock Production

The value of antibiotic alternatives needs to be highlighted as the sustainability of the livestock industry is challenged, due to the rampant use of in-feed antibiotics to maintain pig and poultry gut health. Out of environmental, health, and safety concerns the public is now demanding antibiotic-free pork and poultry meat (e.g., raised without antibiotics and no antibiotics ever). The livestock industry worldwide has shifted to minimize or eliminate the use of in-feed antibiotics to meet growing consumer demands. A viable alternative to in-feed antibiotics must be safe for the public, cost-effective in production, and environmentally friendly. There has been no single “magic bullet” so far that can replace in-feed antibiotics, largely due to the challenge of developing cost-effective alternatives (Omonijo et al., 2018). Probiotics, enzymes, antimicrobial peptides, essential oils, organic acids, and plant extracts have been widely considered to be potential alternatives to in-feed antibiotics. However, the efficacy, consistency of results, and cost-effectiveness of applying these alternatives warrant further investigation. Fundamental advancements in understanding the biological mechanisms underlying their antimicrobial functions are essential before widespread adoption by the industry.

Essential oils (e.g. thymol, eugenol and trans-cinnamaldehyde) are known to have antimicrobial and antioxidative properties, and traditionally have been used as complementary or alternative medicines to improve human health. With the identification of active components in essential oils and some progress in the mechanistic studies of these components in animals, there have been increased research efforts to use essential oils to substitute antibiotics in animal diets (Omonijo et al., 2018). The major barrier for essential oil application in feeds is the fact that they are very volatile and can evaporate rapidly, leading to highly varied final concentrations in feed products affecting their stability during feed processing. Essential oils may be absorbed into feed components and are often completely absorbed in the stomach and the proximal small intestine after oral intake. Therefore, without proper protection, most essential oils will not reach the lower gut of animals where most pathogens reside and propagate and will not offer antimicrobial potential. Microencapsulation has become one of the most popular methods for delivering essential oils and organic acids into the lower gut. Ideally microencapsulation would not only protect the stability of essential oils and organic acids, but also release them at specific intestinal target regions. Many materials including polysaccharides, proteins and lipids have been used to encapsulate essential oils and organic acids for effective delivery. Lipids are currently considered the most cost-effective material for encapsulating essential oils and organic acids in feed.

A recent study indicated that the incorporation of a soy protein-polysaccharide Maillard reaction product stabilized CIT and offered protection to CIT during the storage, upon low pH in the stimulated gastrointestinal tract fluid and heat treatment (Yang et al., 2015). The protection could be due to the incorporation of soy protein-polysaccharide Maillard reaction product (SPPMP) that may have shield peptide bonds against proteolysis and thus slow down the release of CIT from the droplets (Yang et al., 2016). The feed efficiency ratio (FCR), mortality (%), gut lesion scores were all reduced by antibiotics and encapsulated cinnamaldehyde (CIN), citral (CIT) and CIN+CIT. Higher necrotic enteritis (NE) lessions were shown in vaccinated birds but lower in birds fed CIN and CIN + CIT (Yang et al., 2020). The AMR levels (%) of chicken fecal E. coli to most tested antimicrobials were lower in birds fed encapsulated CIN or CIN+CIT which also showed reduced prevalence (%) of some antimicrobial resistance genes (ARGs) (Yang et al., 2021a). Zoonotic potentials of poultry AMR ExPEC extraintestinal pathogenic E. coli (ExPEC) were evaluated by measuring the survival (%) of Caenorhabditis elegans (C. elegans) when exposed to different ExPEC isolates (Yang et al., 2023). ExPEC isolated from poultry meat and feces had significant effects on reducing survival (%) of C. elegans, suggesting that ExPEC isolated from poultry meat or feces may possess zoonotic potential to cause human infections. Encapsulated CIN improved apparent ileal nutrient digestibility, intestinal duodenal and meat quality in broiler chickens (Yang et al., 2021b). Large-scale on-farm trials validated the effectiveness of encapsulated CIN to improve bird health and performance in the absence of antibiotics (Kang et al., 2024).

Using Innovative Chemical Approaches to Detoxify Vomitoxin (DON)

It is worth mentioning that mycotoxin contamination in feeds and feed ingredients can reduce feed intake and compromise the immune system, which can make animals more susceptible to pathogens. Minimizing mycotoxin contamination in feeds is an important component in antibiotic-free animal production. The mycotoxin, deoxynivalenol (DON), commonly occurs on Fusarium-infected cereal grains (e.g., corn, wheat, barley), and the incidence of DON contamination of grains has been increasing in recent years (He et al., 2022). While strategies have been developed to reduce the effects of some mycotoxins (e.g., aflatoxin), such as toxin binders, these have limited effect on mitigating the negative effects of DON (He et al., 2022). There is a need for effective and economical methods to reduce the impact of DON in feed and feed ingredients. Chemical approaches, such as the use of sodium metabisulfite (SMBS) (Dänicke et al., 2010), have shown promise in reducing DON.

Sulphite reducing agents, including SMBS, have the capacity to cleave disulphide cross-linkages (Truong et al., 2016). Specifically, it has been shown that SMBS can destroy from 70% to 100% of DON in processed grains or feeds in vitro with 0.45% to 0.9% levels at pH around 6.5 but not under acidic conditions (Dänicke et al., 2010; 2012). Mwaniki et al. (2021) reported that a feed additive containing SMBS improved growth performance in the nursery piglets fed diets formulated with naturally contaminated corn (formulated with 5.5 mg/kg DON). The results from previous studies have demonstrated that feeding a supplement with relatively high levels of SMB to weanling pigs is safe and effective to detoxify DON. Although the response is still present even without pelleting in many situations, heat and moisture during the pelleting process seem to enhance the capacity of SMBS to detoxify DON. Moreover, SMBS can increase the protein solubility and growth performance of sorghum-based diets in broiler chickens because SMBS can cleave disulphide cross-linkages in protein in sorghum (Selle et al., 2013). However, more than 4% SMBS can reduce voluntary feed intake significantly in broiler chickens (Selle et al., 2013). Because SMBS may be degraded quickly to form sulfur dioxide, then damaging the metabolism of the liver and the functionality of the immune system, eventually leading to a decrease in health or growth performance (Dänicke et al., 2012). This may explain why more than 0.35% of unprotected SMBS in the diet can show toxic effects on pigs. Moreover, little SMBS will remain intact in the small intestine where an optimal pH environment exists for SMBS to detoxify DON (Yu et al., 2021). Thus, there may be a need to deliver intact SMBS to the lower gut such as the small intestine to detoxify DON effectively through innovative delivery methods (Yu et al., 2021). Encapsulated SMBS with hydrogenated palm oil was stable in the simulated gastric fluid and allowed a progressive release of SMBS in the simulated intestinal fluid. The released SMBS in the simulated intestinal fluid effectively detoxified DON (Yu et al., 2021). Further, feeding high SMBS in the diet can decrease the bioavailability of thiamin. So, thiamin may be supplemented at greater concentrations or with a protected form in diets that are supplemented with SMBS.

Limiting Iron Acquisition by Pathogens

Iron is an essential nutrient for both animals and pathogens (Tan et al., 2021). Salmonella strains had better growth when treated with a higher dose of iron, but iron chelators can effectively inhibit the growth of WT and iron uptake-defective mutants of Salmonella and the availability of iron is an important determinant of virulence of Salmonella (Tan et al., 2019). Antibiotic-free diets are currently strongly advocated; therefore, as a nutrition strategy to control iron level and metabolism, it could be a potential weapon to control Salmonella infections in poultry (Tan et al., 2021). In a recent study (unpublished), iron polysaccharide complexes increased the ratio of Firmicutes to Bacteroidetes at the phylum level regardless of environmental hygiene. On the Genus level, iron polysaccharide complexes fed pigs had increased relative abundance of Lactobacillus and Streptococcus. Replacing standard FeSO4 with iron polysaccharide complexes had lower abundance of pathogens in feces from 0 to 14 days, suggesting iron polysaccharide complexes decrease pathogen load. Iron polysaccharide complexes can be alternative iron sources to iron sulfate.

In conclusion, there is still no single “magic bullet” that can replace in-feed antibiotics. It needs to use more than one feed additive that has scientifically proven to support gut health. Minimizing mycotoxin contamination in feeds is also an important component in maintaining animal health and performance in the post-antibiotic world. The host-pathogenic competition for iron suggests that limiting iron acquisition by pathogens can be an effective approach to improve animal health.

Presented at the 2024 Animal Nutrition Conference of Canada. For information on the next edition, click here.