Shortly after the discovery of penicillin in 1929, Alexander Fleming already pointed out the possibility of resistance during an interview with the New York Times. The first case of penicillin resistance was reported only one year after clinical trials began; within 20 years, 80% of Staphylococcus aureus isolates were resistant to penicillin (Lobanovska and Pilla, 2017).

Over the years, clients and patients have gotten used to receiving a pill to quickly fix their ailments. Often, antibiotics have been prescribed for illnesses they were not effective against, including viral challenges. This has unnecessarily accelerated the rate of resistance development. To reverse this trend, education is key. At the same time, the judicious use of antibiotics, meaning the correct antibiotic for the challenge plus proper administration and duration of use, is paramount for all medical professionals to help preserve the efficacy of these critical substances.

Antibiotic use in animal production must be reduced

For many years, animal producers have used antibiotics as growth promoters. The E.U. banned this type of use in 2006, and the United States followed in 2017. Evaluations have shown a decrease in antibiotic use in the U.S.: In 2014, according to the FDA, 17,000 tons of antibiotics were sold in the United States for livestock, representing 80 percent of all U.S. antibiotics sales. In 2019, a total of about 11,000 tons of antibiotics were sold for use in food-producing animals (FDA, 2020).

As the number of isolated multi-drug resistant bacteria increases and the discovery and approval of new antibiotics slows, it is imperative that the use of antibiotics in animal production, especially those that are critically important for humans, is reduced to a minimum. Hence, antibiotics should only be used to treat, control, or prevent diseases in case of imminent risk, but not for growth-promoting purposes.

Scanning electron micrograph of methicillin-resistant Staphylococcus aureus bacteria (yellow) and a dead human white blood cell (red). Credit: National Institute of Allergy and Infectious Diseases/NIH

Customers’ requests for antibiotic-free chicken push antibiotic reduction

Many birds are already raised without antibiotics in the US and elsewhere because of the demands of the market. Since 2016, chicken antibiotic sales decreased by 62% (Dall, 2020). Frequently, the goal of these antibiotic-free (ABF) production programs is to differentiate products in a highly competitive commodity market. The reduction of antibiotic use has been a secondary, generally unintended consequence.

Nevertheless, to meet customer demands for ABF products, antibiotics that are not important to human health but for production (e.g., ionophores) have also been eliminated. In many cases, this has negatively affected growth performance and bird health. As the requirements for production efficiency and welfare standards increase, transitioning from “conventional” to ABF production poses a challenge for everyone involved.

Antibiotic reduction through improved management

One must never trade animal welfare for reduced antibiotics use, but the need for them can be decreased through improved management practices. Flock health starts with genetics companies selecting birds that are resilient to disease and management challenges and continues all the way to the processing plant. All of the inputs and practices must be optimized in modern poultry production to maintain a high level of performance and animal welfare while reducing reliance on antibiotics.

Antibiotic-free requires diligent management

When antibiotics are not available, attention to detail becomes more decisive. All aspects of production are important, but the most critical stages are those that affect the downstream process. The pullets, breeders, and hatchery require the most meticulous care. Additionally, all production factors must meet the highest quality standards: feed, light, air quality, water quality, litter quality, biosecurity, vaccination, sanitation, nutrition and feeding.

Antibiotic reduction requires meticulous attention to detail to safeguard animal welfare.

Non-antibiotic feed additives support ABF programs

ABF production is all about sustainability. For agricultural operations to survive and thrive in the future, one has to move away from the old paradigm of “saving the way to success”. This is not impossible in ABF production, but misses out on the larger picture of long-term profitability, investment in innovation, and system change.

Non-antibiotic feed and water additives are essential resources to support sustainable management. To mention a few, probiotics, prebiotics, toxin binders, organic acids, and phy­tomolecules are all options for reducing the need for antibiotics based on different modes of action. Phytomolecules, for example, often have antimicrobial properties, some toxin binders can bind bacterial toxins, and pre- and probiotics support the gut flora. There are many kinds of solutions on the market; the key is to find the right ones for your issues.

Antibiotic stewardship: together for a healthier future

There is already a large body of literature demonstrating the benefits of alternative or complementary solutions. More importantly, there are already many people that successfully raise birds and other animals without antibiotics. Whenever possible, leverage your professional network and talk to trusted people with unique experiences. Working together, we can build a healthier future for people and animals.

The Antibiotic Reduction series

The series that debuts here consists of a set of articles offering professionals a practical overview of poultry production with reduced antibiotic use. The independent expert in charge, starting with the next article in the series, is Dr. TJ Gaydos, who holds a Master’s degree in Avian Medicine and is a diplomate of the American College of Poultry Veterinarians.

Dr. Gaydos works with integrated poultry companies and allied industries, focusing on bird health and antibiotic-free production performance. He has spent his veterinary career working to improve intestinal health, animal welfare, production efficiency, and reduce zoonotic diseases. He works extensively with intestinal health, probiotics and prebiotics, and other non-antimicrobial feed additives.

Topics covered under Dr. Gaydos’s guidance include biosecurity, nutrition, pullet management, hatchery sanitation, gut health, and more. Together they provide an extensive look at the producers’ pain points and potential strategies to maintain bird health while mitigating the need for antibiotics.

References

AccessScience Editors, “U.S. Bans Antibiotics Use for Enhancing Growth in Livestock.” Access Science. McGraw-Hill Education, January 1, 1970. https://www.accessscience.com/content/u-s-bans-antibiotics-use-for-enhancing-growth-in-livestock/BR0125171.

Dall, Chris. “FDA Reports Another Rise in Antibiotic Sales for Livestock.” FDA Reports Another Rise in Antibiotic Sales for Livestock | International Biosecurity and Prevention Forum, December 16, 2020. https://www.ibpforum.org/news/fda-reports-another-rise-antibiotic-sales-livestock.

Lobanovska, Mariya, and Giulia Pilla . “Penicillin’s Discovery and Antibiotic Resistance: Lessons for the Future?” Yale Journal of Biology and Medicine. 90, no. 1 (March 29, 2017): 135–45.

U.S. Food and Drug Administration. “2020 Summary Report On Antimicrobials Sold or Distributed for Use in Food-Producing Animals” Food and Drug Administration, 2019. https://www.fda.gov/media/144427/download.

by Predrag Persak, Regional Technical Manager North Europe, EW Nutrition

The main sustainability challenge for broiler production lies in securing enough high-quality, nutritious, safe, and readily available food at a reasonable cost. At times, feed ingredients have to be included that are not nutritionally ideal and might compromise one’s broilers’ health and wellbeing. However, counteracting this threat with prophylactic antibiotics is not acceptable: We must minimize the use of antibiotics to mitigate antimicrobial resistance. The way forward is to go beyond static and linear nutritional value-to-price thinking. A dynamic nutritional strategy focusing on the interdependencies between ingredients, gut, microbiome, and digestion, enables sustainable ABF broiler production.

Sustainable ABF broiler production requires a dynamic, gut health-oriented nutritional strategy

Sustainability vs. ABF production – is there a trade-off?

The United Nations’ 1987 Brundtland report offers a clear definition of sustainability as “development that meets the needs of the present without compromising the ability of future generations to meet their own needs.” “Ability” includes the availability of resources – and in broiler production, which is one of the most efficient livestock productions, resources have always been a top priority. As a constantly evolving industry, broiler production has been quick to adopt sustainability into its management strategies. The use of the resource that is antibiotics, however, poses particular challenges.

Humans and animals depend on antibiotics to fight microbial infections. It is essential to maintain their efficacy so that future generations can lead healthy lives. Antibiotic efficacy is under threat from the development of antimicrobial resistance, which emerges from overuse and misuse in both human and veterinary medicine. Across the globe, broilers are still raised with the assistance of antibiotics. Either for disease therapy, to prevent disease occurrence, and still, in some parts of the world, to enhance performance. Driven by regulatory and consumer demands, broiler production with minimal or no use of antibiotics is rapidly gaining importance.

The challenges of antibiotic-free broiler production

ABF systems encounter numerous challenges since production requirements change drastically. Stock density must be lower; it takes longer to reach the desired weight; and more feed is needed to produce the same amount, with a higher risk of morbidity and mortality (Cervantes, 2015). The latter can result in more birds needing treatment with medically important antimicrobial drugs. All those challenges need to be overcome by adopting suitable strategies related to nutrition, genetics, management, biosecurity, welfare, and food safety.

As animal nutritionists, our focus lies on nutrition, feed, feed materials, additives, feed processing, feeding, and their (positive or negative) influence on the sustainability of ABF broiler production. However, we cannot look at these dimensions of production as a separate process. They are linked in the whole food chain and are affected by changes that happen in other related parts. An obvious example is feed production, which has an enormous impact on the overall sustainability of ABF broiler production:

• Due to raw material shortages, diets are becoming ever more complex, containing more single feed ingredients. For some of them, we need a better understanding of their impact on ABF broiler production (e.g., sunflower, rapeseed, beans, lupins).
• The nutritional composition of raw materials changes due to limitations in fertilizer use, and variability within the same raw material group is expected to increase.
• New food waste-reducing feed materials can enhance feed security but also require nutritional profiling to integrate them into diets.
• Local feed material production in humid and warm environments can introduce various pathogens into the feed/food chain.
• Increases in known and the emergence of new antinutrients and feed components that impair animal health, performance, and feed efficiency.
• Sustainability-driven pesticide reduction raises concerns about mycotoxins contaminating feed ingredients.
• Nutrient reduction to support gut health and, primarily, lower the excretion of nitrogen and phosphorous, negatively affects growth, nutritional standards, and the ability to freely select feed materials to include in broiler diets.
• The value (of which price is also part) of raw materials will be compromised, due to availability and nutritional variability.

Mycotoxin contaminated-feed can damage production animals’ performance, health, and welfare

When striving for a sustainable ABF broiler production approach, the possibility for errors becomes higher, while the error margin becomes smaller. The solution lies in helping the animals to mitigate the impact of stressors by focusing on the interaction of ingredients, gut, microbiome, and digestion. It is a holistic approach centered on gut health. Keeping the intestines BEAUTIful will help you produce in challenging conditions without the use of antimicrobials.

Keep the broiler gut BEAUTIful and resilient to stress

The BEAUTIful formula captures the six areas producers need to target for supporting broiler gut health:

Barrier

If it’s working correctly, the effective gatekeeper knows what gets in and what stays out. When the barrier function is compromised due to stress, pathogens can cause infections, disrupt health, and negatively impact broiler immunity. Necrotic enteritis, femoral head necrosis, and bacterial chondronecrosis with osteomyelitis (BCO) are common diseases that affect today’s broiler production (Wideman, 2015). As the source of nutrients, feed serves as a modulator of various physiological functions in the intestinal tract, including intestinal barrier function.

Enzymatic digestion

The gut is where endogenous and exogenous enzymes perform their hydrolysis functions to break down complex nutrients into the parts that can be used either by the intestinal tissue itself or for the whole animal. One part of hybrid enzymatic digestion is the fermentation by commensal microbes, in which complex materials form end-products of high biological values (such as short-chain fatty acids, SCFA).

Absorption

Maintaining the gut’s resorptive capacity is essential to secure the total intake of digested nutrients. Otherwise, pathogenic bacteria might use the excess nutrients to grow, form toxins, and affect the birds’ health and productivity.

United microbiome

The intestine of a broiler chicken is colonized by more than 800 species of bacteria and other inhabitants, such as viruses and simple organisms that are still unknown. By competitive exclusion and secretion of bacteriocins (volatile fatty acids, organic acids, and natural antimicrobial compounds), commensal bacteria keep the host safe from an overgrowth of dangerous bacteria (e.g., Salmonella, Campylobacter, and Clostridium perfringens). The fine-tuned diversity in the intestinal flora and balance in all interactions between it, the host, and the ingesta are needed for birds to stay healthy and perform well.

Transport

Birds’ digestive tract volumes are smaller than those of mammals with similar body weight. This means that they achieve more efficient nutrient digestion in a shorter retention time, averaging between 5 and 6 hours. Passing the small intestine usually takes around 3 hours, of which 1 hour is spent in the duodenum and jejunum. Transport times are affected by the feeding system and the extent to which material enters the caeca. Reflux of material from the distal to the proximal small intestine is an important feature that helps digestion and maintenance of a healthy gut.

Immunity

The intestinal microbiota is critically important for the development and stimulation of the immune system. The intestine is the key immunological organ, comprised of myeloid and lymphoid cells, and a site for producing many immune cell types needed to initiate and mediate immunity. Together with the microbiome, dendritic cells induce antigen-specific responses and form immunoglobulin A, which works in the intestinal lumen.

Natural gut health solution for sustainable ABF broiler production

In practice, supporting broiler gut health requires a holistic approach that includes natural feed additive solutions. Phytomolecules are compounds that certain plants develop as defenses mechanisms. Phytomolecules-based solutions should feature prominently in sustainable ABF broiler production approaches due to their advantageous properties:

Enhance digestion, manage variability

Sustainability necessitates efficient resource utilization. Digestion support needs to be a priority to use the available feed in its entirety. This is particularly important if antibiotics use needs to be minimized: a maximum of nutrients should be utilized by the animal; otherwise, they feed potentially harmful bacteria, necessitating antibiotic treatments. Enhancing digestibility is the focus when we are dealing with variable feed materials or feed changes that represent stress to the animal. Selected phytomolecules have proven efficient at improving performance due to enhanced digestion (Zhai et al. 2018).

Work on microbiome and pathogens

The antimicrobial activity of certain phytomolecules can prevent the overgrowth of pathogens in the gastrointestinal tract, thereby reducing dysbacteriosis (Liu et al., 2018) and specific diseases such as necrotic enteritis. Studies on broilers show that they also reduce the adhesion of pathogens to the wall of the intestine. Certain phytomolecules even possess antimicrobial characteristics against antibiotic-resistant pathogens.

Keep gut integrity

Phytomolecules help maintain tight junction integrity, thus preventing leaky gut (Li et al., 2009). As a result, the potential flow of bacteria and their toxins from the gut lumen into the bloodstream is mitigated. Their properties thus make phytomolecules a promising alternative to the non-therapeutic use of antibiotics. 

Trial results: Phytomolecules enhance broiler gut health

To test the efficacy of phytomolecules, we conducted a large-scale field study in Brazil, under practical conditions. The focus was on growth performance, and no growth-promoting antibiotics were used. Lasting 5 months, the trial involved more than 2 million broilers. The birds were divided into a control and a trial group, with two repetitions per group. Both groups were fed the standard feed of the farm. The trial group additionally received 100g of Activo per MT in its finisher feed for 3 weeks. The study clearly shows that Activo supplementation improves performance parameters (daily weight gain, average total gain, and improved feed efficiency), which resulted in a higher production efficiency factor (PEF):

• Activo groups had a 3 % higher average daily weight gain and reached their slaughtering age earlier
• The final weight of Activo groups was about 2.5 % higher than in the control group
• With a 2 points better feed conversion, the animals of the Activo group achieved a 13.67 points higher PEF

Figure 1: Broiler performance results, Activo vs. non-supplemented control group 

Conclusion

Antibiotic-free broiler production is a challenging endeavor: producers need to maintain animal welfare and keep up efficiency while making farming profitable. Over time, these challenges will affect producers even more as sustainability requirements increase across all parts of the broiler production chain. On top of that, coccidiostats, which are essential for efficient broiler production, are increasingly being questioned, which will require concerted research into feed additive solutions.

To make sustainable ABF broiler production the norm, it is unavoidable to adopt suitable strategies related to nutrition, genetics, management, biosecurity, welfare, and food safety. Effective, scientifically and practically proven tools already exist: Thanks to their positive impact on intestinal health, phytomolecules reliably support sustainable broiler production without antibiotics.

References

Cervantes, Hector M. “Antibiotic-Free Poultry Production: Is It Sustainable?” Journal of Applied Poultry Research 24, no. 1 (2015): 91–97. https://doi.org/10.3382/japr/pfv006.

Li, Y., H.Y. Cai, G.H. Liu, X.L. Dong, W.H. Chang, S. Zhang, A.J. Zheng, and G.L. Chen. “Effects of Stress Simulated by Dexamethasone on Jejunal Glucose Transport in Broilers.” Poultry Science 88, no. 2 (2009): 330–37. https://doi.org/10.3382/ps.2008-00257.

Liu, ShuDong, MinHo Song, Won Yun, JiHwan Lee, ChangHee Lee, WooGi Kwak, NamSoo Han, HyeunBum Kim, and JinHo Cho. “Effects of Oral Administration of Different Dosages of Carvacrol Essential Oils on Intestinal Barrier Function in Broilers.” Journal of Animal Physiology and Animal Nutrition 102, no. 5 (2018): 1257–65. https://doi.org/10.1111/jpn.12944.

Wideman, Robert F. “Bacterial Chondronecrosis with Osteomyelitis and Lameness in Broilers: a Review.” Poultry Science 95, no. 2 (2016): 325–44. https://doi.org/10.3382/ps/pev320.

Zhai, Hengxiao, Hong Liu, Shikui Wang, Jinlong Wu, and Anna-Maria Kluenter. “Potential of Essential Oils for Poultry and Pigs.” Animal Nutrition 4, no. 2 (2018): 179–86. https://doi.org/10.1016/j.aninu.2018.01.005.

Over the past 60 years, antibiotics have played an essential role in the swine industry as a tool that swine producers rely on to control diseases and to reduce mortality. Besides, antibiotics are also known to improve performance, even when used in subtherapeutic doses. The perceived overuse of antibiotics in pig production, especially as growth promoters (AGP), have raised concerns from governments and public opinion, regarding the emergence of multidrug-resistant bacteria, adding a threat not only to animal but also human health. The challenges raised regarding AGPs and the need for their reduction in livestock led to the development of combined strategies such as the “One Health Approach”, where animal health, human health, and the environment are interlaced and must be considered in any animal production system.

In this scenario of intense changes, swine producers must evaluate strategies to adapt their production systems to accomplish the global pressure to reduce antibiotics and still have a profitable operation.

Many of these concerns focus on piglet nutrition, since the use of sub-therapeutic levels of antimicrobials as growth promotors is still a regular practice for preventing post-weaning diarrhea in many countries (Heo et al., 2013; Waititu et al., 2015). Taking that into consideration, this article serves as a practical guide to swine producers through AGP removal and its impacts on piglet performance and nutrition Three crucial points will be addressed:

1. Why is AGP removal a global trend?
2. What are the major consequences for piglet nutrition and performance?
3. What alternatives do we have to guarantee optimum piglet performance in this scenario?

AGP removal: a global issue

Discussions on the future of the swine industry include understanding how and why AGP removal became such important topic worldwide. Historically, European countries have led discussions on eliminating AGP from livestock production. In Sweden, AGPs were banned from their farms as early as 1986. This move culminated into a total ban of AGPs in the European Union in 2006. Other countries followed same steps. In Korea, AGPs were removed from livestock operations in 2011. The USA is also putting efforts into limiting AGPs and the use of antibiotics in pig farms, as published in guidance revised by the Food and Drug Administration (FDA, 2019). In 2016, Brazil and China banned Colistin, and the Brazilian government also announced the removal of Tylosin, Tiamulin, and Lincomycin in 2020. Moreover, countries like India, Vietnam, Bangladesh, Buthan, and Indonesia have announced strategies for AGP restrictions (Cardinal et al., 2019; Davies and Walsh, 2018).

The major argument against AGPs and antibiotics in general is the already mentioned risk of the development of antimicrobial resistance, limiting the available tools to control and prevent diseases in human health. This point is substantiated by the fact that resistant pathogens are not static and exclusive to livestock, but can also spread to human beings (Barbosa and Bünzen, 2021). Moreover, concerns have been raised in regard to the fact that antibiotics in pig production are also used by humans – mainly third-generation antibiotics. The pressure on pig producers increased and it is today multifactorial: from official regulatory departments and stakeholders at different levels, who need to consider public concerns about antimicrobial resistance and its impact on livestock, human health, and the sustainability of farm operations (Stein, 2002).

It is evident that the process of reducing or banning antibiotics and AGPs in pig production is already a global issue and increasing as it takes on new dimensions. As Cardinal et al. (2019) suggest, that process is irreversible. Companies that want to access the global pork market and comply with increasingly stricter regulations on AGPs must re-invent their practices. This, however, is nothing new for the pig industry. For example, pig producers from the US and Brazil have adapted their operations in order to not use ractopamine to meet the requirements from the European and Asian markets. We can be sure, therefore, that the global pig industry will find a way to replace antibiotics.

With that in mind, the next step is to evaluate the consequences of AGP withdrawal from pig diets and how that affects the animals’ overall performance.

Consequences in piglet health and performance

Swine producers know very well that weaning pigs is challenging. Piglets are exposed to many biological stressors during that transitioning period, including introducing the piglets to new feed composition (going from milk to plant-based diets), abrupt separation from the sow, transportation and handling, exposure to new social interactions, and environmental adaptations, to name a few. Such stressors and physiological challenges can negatively impact health, growth performance, and feed intake due to immune systems dysfunctions (Campbell et al. 2013). Antibiotics have been a very powerful tool to mitigate this performance drop. The question then is, how difficult can this process become when AGPs are removed entirely?

Many farmers around the world still depend on AGPs to make the weaning period less stressful for piglets. One main benefit is that antibiotics will reduce the incidence of PWD, with subsequent improved growth performance (Long et al., 2018). The weaning process can create ideal conditions for the overgrowth of pathogens, as the piglets’ immune system is not completely developed and therefore not able to fight back. Those pathogens present in the gastrointestinal tract can lead to post-weaning diarrhea (PWD), among many other clinical diseases (Han et al., 2021). PWD is caused by Escherichia coli and is a global issue in the swine industry, as it compromises feed intake and growth performance throughout the pig’s life, also being a common cause for losses due to young pig death (Zimmerman, 2019).

Cardinal et al. (2021) also highlight that the hypothesis of a reduced intestinal inflammatory response is one explanation for the positive relationship between the use of AGPs and piglet weight gain.  Pluske et al. (2018) point out that overstimulation of the immune system can negatively affect pig growth rate and feed use efficiency. The process is physiologically expensive in terms of energy and also can cause excessive prostaglandin E2 (PGE2) production, leading to fever, anorexia, and reduction in pig performance. For instance, Mazutti et al. (2016) showed an increased weight gain of up to 1.74 kg per pig in animals that received colistin or tylosin in sub-therapeutic levels throughout the nursery. Helm et al. (2019) found that pigs medicated with chlortetracycline in sub-therapeutic levels increased average daily gain in 0.110 kg/day. Both attribute the higher weight to the decreased costs of immune activation determined by the action of AGPs on intestinal microflora.

On the other hand, although AGPs are an alternative for controlling bacterial diseases, they have also proved to be potentially deleterious to the beneficial microbiota and have long-lasting effects caused by microbial dysbiosis – abundance of potential pathogens, such as Escherichia and Clostridium; and a reduction of beneficial bacteria, such as Bacteroides, Bifidobacterium, and Lactobacillus (Guevarra et al., 2019; Correa-Fiz, 2019). Furthermore, AGPs reduced microbiota diversity, which was accompanied by general health worsening in the piglets (Correa-Fiz, 2019).

It is also important to highlight that the abrupt stress caused by suckling to weaning transition has consequences in diverse aspects of the function and structure of the intestine, which includes crypt hyperplasia, villous atrophy, intestinal inflammation, and lower activities of epithelial brush border enzyme (Jiang et al., 2019). Also, the movement of bacteria from the gut to the body can occur when the intestinal barrier function is deteriorated, which results in severe diarrhea and growth retardation. Therefore, nutrition and management strategies during that period are critical, and key gut nutrients must be used to support gut function and growth performance.

With all of that, it is more than never necessary to better understand the intestinal composition of young pigs and finding strategies to promote gut health are critical measures for preventing the overgrowth and colonization of opportunistic pathogens, and therefore being able to replace AGPs (Castillo et al., 2007).

Viable alternatives for protecting the piglets

The good news is that the swine industry already has effective alternatives that can replace AGP products and guarantee good animal performance.

Immunoglobulins from egg yolk (IgY) have proven to be a successful alternative to weaned piglet nutrition. Investigations have shown that egg antibodies improve the piglets’ gut microbiota, making it more stable (Han et al., 2021). Moreover, IgY optimizes piglet immunity and performance while reducing occurrences of diarrhea caused by E. coli, rotavirus, and Salmonella sp. (Li et al., 2016).

Phytomolecules (PM) are also potential alternatives for AGP removal, as they are bioactive compounds with antibacterial, antioxidant, and anti-inflammatory characteristics (Damjanović-Vratnica et al., 2011; Lee and Shibamoto, 2001). When used for piglet diet supplementation, phytomolecules optimize intestinal health and improve growth performance (Zhai et al., 2018).

Han et al. (2021) evaluated a combination of IgY (Globigen^® Jump Start, EW Nutrition) and phytomolecules (Activo^®, EW Nutrition) supplementation in weaned piglets’ diets. Results from that study (Table 1 and 2) showed that this strategy decreases the incidence of PWD and coliforms, increases feed intake, and improves the intestinal morphology of weaned pigs, making that combination a viable AGP replacement.

Table 1. Effect of dietary treatments on the growth performance of weaned pigs challenged with E. coli K88 (SOURCE: Han et al., 2021).

Table 2. Effect of dietary treatments on the post-weaning diarrhea incidence of weaned pigs challenged with E. coli K88 (%) (SOURCE: Han et al., 2021).

A trial conducted at the Institute of Animal Sciences of the Chinese Academy of Agricultural Sciences, China, supplemented weaning pigs challenged by E. coli K88 with a combination of PM (Activo^®, EW Nutrition) and IgY (Globigen^® Jump Start). The trial reported that this combination (AC/GJS) showed fewer diarrhea occurrences than in animals from the positive group (PC) during the first week after the challenge and similar diarrhea incidence to the AGP group during the 7th and 17th days after challenge (Figure 1).

Figure 1 – Incidence of diarrhea (%). NC: negative group, PC: positive group, AGP: supplementation with AGP, AC/GJS: combination of PM (Activo, EW Nutrition) and IgY (Globigen Jump Start).

The same trial also showed that the combination of these non-antibiotic additives was as efficient as the AGPs in improving pig performance under bacterial enteric challenges, showing positive effects on body weight, average daily gain (Figure 2), and feed conversion rate (Figure 3).

Figure 2 – Body weight (kg) and average daily gain (g). NC: negative group, PC: positive group, AGP: supplementation with AGP, AC/GJS: combination of PM (Activo, EW Nutrition) and IgY (Globigen Jump Start).

Figure 3 – Feed conversion rate. NC: negative group, PC: positive group, AGP: supplementation with AGP, AC/GJS: combination of PM (Activo, EW Nutrition) and IgY (Globigen Jump Start).

The multiple benefits of using IgY in piglet nutrition strategies are also highlighted by Rosa et al. (2015), Figure 4, and Prudius (2021).

Figure 4. Effect of treatments on the performance of newly weaned piglets. Means (±SEM) followed by letters a,b,c in the same group of columns differ (p < 0.05). NC (not challenged with ETEC, and diet with 40 ppm of colistin, 2300 ppm of zinc, and 150 ppm of copper). Treatments challenged with ETEC: GLOBIGEN® (0.2% of GLOBIGEN®); DPP (4% of dry porcine plasma); and PC (basal diet) (SOURCE: Rosa et al., 2015).

Conclusions

AGP removal and overall antibiotic reduction seems to be the only direction that the global swine industry must take for the future. From the front line, swine producers demand cost-effective AGP-free products that don’t compromise growth performance and animal health. Along with this demand, finding the best strategies for piglet nutrition in this scenario is critical in minimizing the adverse effects of weaning stress. With that in mind, alternatives such as egg immunoglobulins and phytomolecules are commercial options that are already showing great results and benefits, helping swine producers to go a step further into the future of swine nutrition.

References

Damjanović-Vratnica, Biljana, Tatjana Đakov, Danijela Šuković and Jovanka Damjanović, “Antimicrobial effect of essential oil isolated from Eucalyptus globulus Labill. from Montenegro,” Czech Journal of Food Sciences 29, no. 3 (2011): 277-284.

Pozzebon da Rosa, Daniele, Maite de Moraes Vieira, Alexandre Mello Kessler, Tiane Martin de Moura, Ana Paula Guedes Frazzon, Concepta Margaret McManus, Fábio Ritter Marx, Raquel Melchior and Andrea Machado Leal Ribeiro, “Efficacy of hyperimmunized hen egg yolks in the control of diarrhea in newly weaned piglets,” Food and Agricultural Immunology 26, no. 5 (2015): 622-634. https://doi.org/10.1080/09540105.2014.998639

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by Ruturaj Patil, Product Manager Phytogenic Liquids, EW Nutrition

Commercial poultry operations have undergone enormous changes in production practices over the last 50 years. Genetic selection for high production rates, along with upgraded management techniques and dietary measures, have led to increased performance standards in all poultry operations (Kogut et al., 2017). However, it is sensible to now look into whether poultry performance may soon reach a ceiling due to genetic and/or physiological limits. So, aiming at further performance optimization, poultry researchers and producers are now focusing on gut health.

Gut health management is key to sustainably improve poultry performance

The caveat, of course, is that, due to concerns about antimicrobial resistance, antimicrobial growth promoters (AGPs) no longer offer the easy answer to gut health issues they once were. To preserve antibiotics’ efficacy for cases where they are indispensable, gut health-oriented performance enhancement needs to come from other sources. This article reviews the principles of gut health management in poultry and shows how Activo liquid, a phytomolecules-based in-water solution, strengthens poultry performance by targeting gut health.

Gut health: the cradle of poultry performance

Gastrointestinal health in poultry birds encompasses three dimensions: microflora balance, gut structural integrity, and immune system status. The gut plays a vital and diverse role as it hosts most microorganisms in the body, contains more than twenty different hormones, digests and absorbs the nutrients, and accounts for 20% of body energy expenditure (Choct, 2021). When gut health is compromised, digestion and nutrient absorption are affected, with likely detrimental effects on feed conversion, followed by economic loss and greater disease susceptibility.  Disease resistance and nutrient utilization largely depend on maintaining a beneficial gut antioxidant status, improving gut integrity, and modulating the gut microbiota (Oviedo-Rondón, 2019).

In birds, the gut is separated into five distinct regions (Figure 1): crop, proventriculus, gizzard, small intestine (duodenum, jejunum, and ileum), and large intestine (ceca, cloaca, and vent). Each of these regions has a specific role in the secretion of digestive juices and enzymes, the grinding of feed particles and then the digestion and absorption of nutrients (Bailey 2019).

Figure 1: Schematic overview of poultry gastrointestinal tract

Factors affecting gut health

Gut health is influenced by the balance between the physiological health status of host, the gut microbiota, and a range of specific factors, all of which producers need to consider. From a management perspective, key factors encompass deprived gut health, biosecurity, and production stress, which is elevated during certain critical stages (see table 1). Environmental factors include humidity, temperature, and ventilation. Dietary factors, such as feed and water quality, feed composition, and mycotoxin contamination, also impact the development and ongoing state of poultry birds’ intestinal microbiota.

Table 1: Critical stages for gut health issues in poultry birds

The future is here: antibiotic reduction through improved gut health

There is a strong trend towards antibiotic-free (ABF) poultry production, fueled by AGP bans in certain regions (such as the European Union) and increasing consumer interest in avoiding products containing traces of AGPs. ABF systems can be profitable as long as the prices for the final ABF products can cover the investment costs necessary to produce these products. Larger-scale, sustainable ABF production will depend on developing a more profound understanding of intestinal health alongside the development of practical applications that foster gut health throughout each step of the production system.

Feed additive solutions to support birds during challenging situations

Feed additive manufacturers are looking into accessible alternatives to mitigate the need for antibiotics in ABF systems, requiring enormous research and development efforts. At EW Nutrition, our approach is to offer a holistic antibiotic reduction program for gut health management in poultry. The program comprises feed- and water-based solutions to support gut health during high-challenge periods. Activo liquid, an in-water solution containing standardized amounts of selected phytomolecules, is a key component of our program. Based on its three-fold mode of action, Activo liquid provides gut health support that improves livability and feed efficiency:

• Antimicrobial activity hinders the growth of potential pathogens
• Better gut integrity and positive microbiota optimize feed efficiency and gut health
• Antioxidant activity at the gut level prevent free radical formation and oxidative stress

As a water-based solution, Activo liquid provides a quick and flexible option for gut health control on poultry farms. The benefits of Activo liquid supplementation have been demonstrated through several scientific and field studies globally.

Activo liquid reduces mortality and improves feed conversion in broilers

Numerous field studies for antibiotic-free broilers across different countries and breeds show: on average, the inclusion of Activo liquid reduces mortality by 0.6% and improves FCR by 5%, compared to non-supplemented control groups (Figure 2).

Figure 2: Changes in livability and feed conversion rate in Activo liquid-supplemented broilers

Activo Liquid supports broiler breeders from start of lay to pre-peak production

Broiler breeders are prone to gut-related issues from the start of lay to pre-peak production (age 24 to 32 weeks). This period is characterized by sudden changes in feed consumption and high production stress. Field studies from Thailand show that Activo liquid supplementation in this phase leads to improved livability and higher laying rates.

A of 34,000 female broiler breeders during the first 9 weeks of production found that for the group receiving Activo Liquid  (200 ml / 1000 L, 5 days per week, 6 hours per day):

• The average laying rate/HH increased by 7.2 % during the trial period,
• Nearly 3  more  hatching  eggs  per  hen  housed  and  about  5  more  hatching  eggs  than  the  genetic standard were produced, and
• Mortality decreased by 0.2 % points compared to the control.

Another study, again evaluating the first 9 weeks of production using 20,000 birds, also found that broiler breeders supplemented with  Activo  Liquid show reduced mortality, a higher laying rate, and more hatching eggs per hen housed (Figure 3).

Figure 3: Performance results from Cobb broiler breeders, Activo liquid supplementation vs. control

Activo program improves layer productivity

Commercial layers often becomes challenged due to stress originating from management issues, gut pathogens, and an improper assimilation of nutrients. The negative impact on gut health can result in poor uniformity, low livability, and impaired body weight gain. The Activo program (a combination of Activo powder and liquid) has been found to improve layer performance, likely because its phytogenic components foster better intestinal integrity and microbiome diversity.

A study of 8 replicates with 36 Hy-line brown laying hens was conducted in China, for instance, testing the inclusion of both Activo (100 g / MT of feed) and Activo Liquid (250 ml / 1000 L for 4 days, every 2 weeks, from week 15 to week 25). It found that the Activo program  can effectively support the animals in coping with NSP-rich diets (Figure 4). Supplemented layers showed 3.36% higher egg production, representing more than 3.5 eggs and more than 150 grams of additional egg mass per hen housed during the period.  Better  gut  health  in  the  Activo  Program  gut  was evidenced  by  a  better  hen  body  weight ,  as  well  as  higher  yolk  color, lower  FCR, and improved  intestinal morphology parameters.

Figure 4: Performance results from Hy-line layers, Activo program vs. control

Conclusion: future improvements in poultry performance will come from the gut

As the trend towards ABF poultry production gains momentum, a concerted focus on supporting birds’ gut health is key to achieving optimal performance. Multiple field studies of Activo liquid application demonstrate that, due to their antimicrobial and antioxidant properties, the phytomolecules present in Activo liquid effectively support birds’ intestinal health during challenging periods.

In combination with good dietary, hygiene and management practices, phytomolecules offer a potent tool for reducing the use of antibiotics. The inclusion of Activo liquid in their birds’ diets allows poultry producers to achieve better gut health and, thus, stronger performance results in a sustainable way.

References

Bailey, Richard A. “Gut Health in Poultry: the World within – Update.” The Poultry Site, July 6, 2021. https://www.thepoultrysite.com/articles/gut-health-in-poultry-the-world-within-1.

Choct, Mingan. “The Importance of Managing Gut Health in Poultry.” Poultry Hub Australia, November 26, 2014. https://www.poultryhub.org/importance-managing-gut-health-poultry.

Kogut, Michael H., Xiaonan Yin, Jianmin Yuan, and Leon Bloom. “Gut Health in Poultry.” CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources 12, no. 031 (October 1, 2017): 1–7. https://doi.org/10.1079/pavsnnr201712031.

Oviedo-Rondón, Edgar O. “Holistic View of Intestinal Health in Poultry.” Animal Feed Science and Technology 250 (2019): 1–8. https://doi.org/10.1016/j.anifeedsci.2019.01.009.

by Dr. Ajay Bhoyar, Global Technical Manager – Poultry, EW Nutrition

Necessity, goes the saying, is the mother of invention. No wonder, then, that necessity is driving innovation in the poultry industry.  A few distinct such drivers of change stand out:

Genetic improvements: Significant genetic improvements have consistently increased the production performance of breeders, as well as commercial broilers and layers. The genetically improved breeds demand improved nutrition and management practices.

Feed ingredient prices/availability: Corn and soybean meal are the main feed ingredients in poultry feed. Consequently any fluctuations in their prices have a high impact on the cost of production of eggs and meat. During the short span of the last 5 years, US corn and soybean meal prices have increased by around 54% and 68%, respectively. The optimum utilization of available feed ingredients and improvements in nutrient availability continue to be the key areas of interest for the poultry industry.

Consumer preference and regulatory changes: In certain geographies, these changes have resulted into 3 major trends in the poultry industry: antibiotics reduction (ABR), cage-free rearing, and food safety. The trend in the production and consumption of antibiotic-free meat products is growing faster than ever across the globe.

Antibiotics reduction (ABR): a key global trend

Apart from veterinary use, antibiotics are used as feed additives —antibiotic growth promoters (AGP) in animal production. Alarming levels of resistance to antibiotics have been reported in countries of all income levels, with the result that common diseases are becoming untreatable, and life-saving medical procedures riskier to perform.  Misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens. (WHO/ https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance )

Antibiotic-free chicken production has gained a lot of momentum in the recent past. Over the past years, consumer preferences in the US resulted in a significant increase in the production of antibiotics-free (ABF) broiler chicken meat. In effect, the number of birds produced in “no antibiotics ever” (NAE) programs in the U.S. today is now at more than 50 percent (Poultry Health Today, 2019).

The reduction of antibiotic use poses some challenges to poultry producers. Apart from increased capital investment for modifications in feed mills and farms, increase in feed additive cost, the main challenge due to the removal of AGPs from feed can be the reduced production performance of poultry, mainly due to increased gut health issues.

Good gut health is a must for profitable production

“The intestinal health of poultry has broad implications for the systemic health of birds, animal welfare, the production efficiency of flocks, food safety, and environmental impact,” state Oviedo-Rondón (2019). The main challenges for ABF chicken or turkey production fall under the same heading of gut health, in particular the prevention and control of coccidiosis and necrotic enteritis (Cervantes, 2015).

What are the most effective ways to mitigate gut health challenges?

Depending on specific production needs and challenges, various technologies are used by the poultry producers to address gut health issues. Some of the most commonly used innovative technologies include:

Dietary Fibers (DF)

Scientists have found that DF have an enormous impact on the gastrointestinal tract (GIT) development, digestive physiology, including nutrient digestion, fermentation, and absorption processes of poultry (Jha & Mishra, 2021).

The water-insoluble fibers are seen as functional nutrients, as they can escape digestion and modulate nutrient digestion: “A moderate level of insoluble fiber in poultry diets may increase chyme retention time in the upper part of the GIT, stimulating gizzard development and endogenous enzyme production, improving the digestibility of starch, lipids, and other dietary components” (Mateos et.al. 2012). The insoluble DF, when used in amounts between 3–5% in the diet, could have significant effects on intestinal development and nutrient digestibility.

Dietary fibers influence the development of the gizzard in poultry birds.  A well-developed gizzard is a must for good gut health. Jiménez-Moreno & Mateos (2012) noted that the coarse fiber particles are selectively retained in the gizzard, that ensures a complete grinding and a well-regulated feed flow and secretion of digestive juices, and regulates GIT motility & feed intake. The inclusion of insoluble fibers in adequate amounts improves the gizzard function and stimulates HCl production in the proventriculus. Thus it can help in the control of gut pathogens.

Probiotics and prebiotics

Probiotics and prebiotics have drawn considerable attention as alternatives to antibiotics in animal feeds. Supplementing diets with probiotics and prebiotics is a significant factor contributing to modified intestinal microflora, which, in turn, may effectively influence the birds’ growth performance and health (Yang et al. 2009).

Probiotics introduce desirable microorganisms into the intestinal tract through the diet (feed or water). They consist of live bacteria, fungi, or yeasts that positively contribute to the gastrointestinal flora. As such, they are important for a well-formed and well-maintained digestive system, and are indirectly essential to growth performance and to the overall health of animals in general. Probiotic supplementation could have the following effects, as stated by Jha et al:

• modification of the intestinal microbiota
• stimulation of the immune system
• reduction in inflammatory reactions
• prevention of pathogen colonization
• enhancement of growth performance
• alteration of the ileal digestibility and total tract apparent digestibility coefficient
• decrease in ammonia and urea excretion (Jha et.al., 2020)

Probiotics can be used not just in feed and drinking water, but also in spray solutions applied to day-old chicks either in the hatchery or immediately after placement in the brooding house. This way, the beneficial microorganisms can enter the intestine earlier than through other methods (known as early seeding).

Prebiotics are also a means of increasing the beneficial bacteria in the poultry gut microbiota. Prebiotics like mannan-oligosaccharides (MOS), inulin and its hydrolysate (fructooligosaccharides: FOS), as well as other prebiotics are important contributors to the modulation of the intestinal microflora and stimulating a potential immune response, as well as stimulating the development of beneficial microorganisms. Prebiotics can also help reduce pathogen colonization in the GIT.

Feed enzymes

The role of feed enzymes in promoting the efficiency of nutrient utilization is well recognized. Recent estimates (Adeola & Cowieson, 2011) indicate that feed enzymes saved the global feed market an estimated US $3–5 billion per year. Feed Enzymes can also have a positive impact on gut health.

Among the beneficial effects of feed enzymes are:

• Inactivating anti-nutrients in the feed ingredients
• Unlocking nutrients otherwise unavailable to birds (e.g. Phosphorus from phytic acid)
• Reducing harmful microbial proliferation, depriving detrimental microorganisms of nutrients
• Reducing the undigestible components of feed, the viscosity of digesta, or the irritation to the gut mucosa that causes inflammation.

Enzymes also generate metabolites that promote microbial diversity, which helps to maintain gut ecosystems that are more stable and more likely to inhibit pathogen proliferation (Bedford, 1995; Kiarie et al., 2013). Feed enzymes are heat-sensitive and tend to lose their activity potential during pelleted feed manufacturing. There has been a significant interest in the application of intrinsically heat stable enzymes for more efficient action. Apart from coated feed enzymes, the post pellet liquid application (PPLA) of feed enzymes has increased in the recent past.

Toxin binders & antioxidants

Intestinal health problems can often be preempted, especially in poultry companies with ABF production programs, by mitigating the danger of mycotoxins in feedstuffs and rancid fats (Murugesan et al., 2015; Grenier and Applegate, 2013). Mycotoxins can compromise several key functions of GIT. This often results in decreased nutrient absorption (by decreasing the available surface area), modulation of nutrient transporters, and loss of barrier function (Grenier and Applegate, 2013). Some mycotoxins “encourage” the persistence of intestinal pathogens and thus enhance the possibility of intestinal inflammation.

Rancid fats and oils have been linked to the pathogenesis of enteric diseases (Hoerr, 1998; Butcher and Miles, 2000; Collet, 2005). The oxidation of oils and fats negatively impacts the energy content of these ingredients. The addition of feed antioxidants during the rendering process/ blending of fats and oils, and proper storage and transport before final use in feed can control rancidity in oils and fats. Proper fat storage conditions in tanks and transportation lines should be constantly monitored to prevent the development of rancidity in the feed mill. Antioxidants and mycotoxin binders can reduce the effects of mycotoxins and peroxide, especially, but not only, in ABF programs (Yegani and Korver, 2008).

Organic acids

Organic acids are compounds with acidic properties that occur naturally and include carbon. As the digestive process includes microbial fermentation, beneficial bacteria which naturally reside in the crop, intestines, and ceca produce such organic acids (Huyghebaert et.al. 2010). The inclusion of organic acids in poultry diets can improve gut health, increase endogenous digestive enzyme secretion and activity, and improve nutrient digestibility. Thus they generally contribute to the overall gut health of the animal.

The inclusion of organic acids in feed can help not only decontaminate feed but also have the potential to reduce enteric pathogens in poultry. The acids can cross the bacterial cell wall and disrupt the normal actions of certain types of bacteria, including Salmonella spp, E. coli, Clostridia spp, Listeria spp. and some coliforms.

Organic acids are also used in drinking water to help lower the microbial count. This can be achieved by lowering the pH of water and by the prevention/removal of biofilms in the water lines.

However, organic acids should be included in the feed or water with caution. The limitations for use of organic acids in animal production can be:

• Bacterial resistance to organic acids over long-term use
• Adverse effect on feed palatability, leading to feed refusal
• Organic acids are corrosive in nature and can damage poultry equipment
• Buffering capacity of dietary ingredients can impact efficacy

Essential oils/Phytomolecules

Essential oils (EOs) are raw extracts from plants (herbs, flowers, leaves, roots, fruit etc.). The beneficial effects of EOs include appetite stimulation, improvement of enzyme secretion related to food digestion, and immune response activation (Krishan and Narang, 2014)

EOs are an unpurified mix of different phytomolecules. The raw extract from oregano is a mix of various phytomolecules (terpenoids) like carvacrol, thymol, and p-cymene. Carvacrol, for instance, is a monoterpinoid found in various plants such as oregano or thyme. A phytomolecule is one active compound.

These botanicals have received increased attention as possible growth performance enhancers for animals in the last decade because of their beneficial influence on lipid metabolism, as well as their antimicrobial and antioxidant properties (Botsoglou et al., 2002), their ability to stimulate digestion (Hernandez et al., 2004), their immune-enhancing activity, and anti-inflammatory potential (Acamovic and Brooker, 2005). Many studies have reported on the supplementation of poultry diets with essential oils that enhanced weight gain, improved carcass quality, and reduced mortality rates (Williams and Losa, 2001). The use of specific EO blends can be effective in reducing the colonization and proliferation of Clostridium perfringens and controlling coccidia infections. Consequently, it may also help reduce necrotic enteritis (Guo et al., 2004; Mitsch et al., 2004; Oviedo-Rondón et al., 2005, 2006a, 2010).

Mode of action of phytomolecules

The gut health optimizing mode of action of phytomolecule-based preparations like Activo® (EW Nutrition) can be described as follows:

Digestive

The digestive properties increase the secretion of digestive enzymes and enhance gut motility. A “significant increase in pancreatic trypsin, amylase, and maltase activities in broilers fed different blends of commercial essential oils” has been reported as well (Jang et al., 2007). The essential oils in carvacrol, for instance, have positive effects on growth performance and the intestinal barrier function of broilers. They were also able to support repairing the intestinal damage caused by lipopolysaccharides (Liu et al. 2020).

Antimicrobial

The antimicrobial properties of phytomolecules can impede the growth of potential pathogens. Thymol, eugenol, and carvacrol have been shown to have “synergistic or additive antimicrobial effects when combined at lower concentrations” (Bassolé and Juliani, 2012). In in vivo studies, essential oils used either individually or in combination “have shown clear growth inhibition of Clostridium perfringens and E. coli in the hindgut and ameliorated intestinal lesions and weight loss than the challenged control birds” (Jamroz et al., 2006, Jerzsele et al., 2012, Mitsch et al., 2004).

One well-known mechanism of antibacterial activity is linked to the phytomolecules’  hydrophobic nature. This characteristic helps disrupt the permeability of cell membranes and cell homeostasis. The consequence of this disruption is the loss of cellular components, influx of other substances, or even cell death (Brenes and Roura, 2010, Solórzano-Santos and Miranda-Novales, 2012, Windisch et al., 2008, O’Bryan et al., 2015).

Antioxidant

The antioxidant properties at the gut level prevent free radical formation and oxidative stress. Thymol and carvacrol have been shown to inhibit lipid peroxidation (Hashemipour et.al. 2013), a mechanism leading to the oxidative destruction of cellular membranes (Rhee et al., 1996). This destruction can ultimately lead to cell death and to the production of toxic and reactive aldehyde metabolites, known as free radicals. Among these free radicals, malondialdehyde (MDA) as a final product of lipid peroxidation has often been used for determining oxidative damage (Jensen et al., 1997).  Thymol and carvacrol both have strong antioxidant activity (Yanishlieva et al., 1999). Oregano “added in doses of 50 to 100 mg/kg to the diet of chickens exerted an antioxidant effect in the broiler tissues” (Botsoglou et al., 2002).

It has also been suggested that chicken body oxidative balance can benefit from essential oils. Karadas et al. (2014) fed a blend of carvacrol, cinnamaldehyde, and capsicum oleoresin to Ross 308 broilers, and found a significant increase in the hepatic concentration of carotenoids and coenzyme Q10 at d 21 of age.

Essential oils, or phytomolecules, are highly volatile substances and are susceptible to changes caused by external factors such as light, oxygen, and temperature, in addition to being prone to evaporating. They need to be protected/micro-encapsulated during the process of feed manufacturing. The advantages of matrix encapsulation include

• a slow and gradual release of active ingredients in the digestive tract
• protection of phytomolecules from oxidation and other harsh conditions during feed processing
• prevention of any negative effects on palatability of feed

Above: Micro-encapsulation protecting phytomolecules in feed processing

Apart from use in feed, the liquid phytomolecules preparations for drinking water use can prove to be beneficial in preventing and controling losses during challenging periods of the birds’ life (feed change, handling, environmental stress, etc.).  The liquid preparations have the potential to reduce morbidity and mortality in poultry houses and thus the use therapeutic antibiotics. Barrios et al. (2021) suggested that Activo and Activo Liquid may ameliorate the impact of Necrotic Enteritis on broilers and further hypothesized that the effects of Activo Liquid were particularly important in improving overall mortality.

Conclusion

The prevailing driving forces of the market will continue to challenge the dynamic poultry industry. Still, gut health challenges in ABF poultry production can be alleviated with multifactorial approaches, including changes in nutrition and improved management practices. Innovative feed additive technologies have contributed to reducing production losses triggered by the removal of AGPs in poultry production.

Essential oils/phytomolecules are one such promising technology, with proven benefits in terms of the production performance of poultry. Phytomolecules are generally recognized as safe and are commonly used in the food industry. Some of the phytomolecules combinations have multiple modes of action, supporting an efficient and sustainable reduction in antibiotics use in poultry production.

To make ABF programs successful, however, more attention needs to be given to the whole production system, not only to feed, feed additives or control of a few enteric pathogens. Housing, management, water quality and biosecurity at both breeder and grow-out levels are critical in ABF production.

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by EW Nutrition USA, Inc.

In the poultry industry, Necrotic Enteritis is of great interest due to the potential detrimental growth effects it may have in a flock, even at subclinical levels⁵⁰. Coccidiostats and antibiotics have been used for a long time to get the disease-causing bacterium Clostridium perfringens under control, but with increasing antimicrobial resistance, alternative approaches are required. This article aims to give an overview of the disease and the measures against it.

Clostridium perfringens – a ubiquitous, highly resilient bacterium

Clostridium perfringens is a Gram-positive, spore-forming, anaerobic, rod-shaped bacterium⁵⁰. This encapsulated, non-motile microorganism is fastidious in growth requirements⁵⁹. Most often, complex media like cooked meat or thioglycolate broth are used as enrichment³⁰.

It was Welch and Nuttall who first identified C. perfringens in 1892 as Bacillus aerogenes capsulatus¹⁸. In Great Britain, the bacterium was commonly known as C. welchii and sometimes called Frankel’s bacillus in Germany until designated C. perfringens by Bergey¹³.

Clostridium perfringens is the causal microorganism for Necrotic Enteritis (NE)¹⁴. In humans, it is one of the most common causes of foodborne illness²⁰. The Centers for Disease Control and Prevention (CDC, 2012) estimates that nearly one million people are affected every year, making C. perfringens the third most frequent source of domestically acquired foodborne illness after Norovirus and Salmonella.

Clostridium perfringens can be found everywhere

Clostridium perfringens is found in soil, water, and other organic materials. As far as poultry facilities, C. perfringens has been isolated from litter, dust, walls, floors, fans, transportation coops, feeders, and feed⁸⁹.

Additionally, C. perfringens is found in the GI tract of broiler chickens, humans, and other mammals⁴⁷. When intestinal samples of broiler chickens were analyzed for C. perfringens, 75-95 % tested positive²⁴. Drew and co-workers¹⁰ determined that C. perfringens is usually found at ~10⁴ colony-forming units (CFU)/g of broiler digesta. These results agree with Jia et al.²⁶, who stated that C. perfringens is present at low levels in healthy poultry. In humans, investigations in different parts of the world showed a prevalence of Clostridium perfringens between 57-94%³².

Different types of Clostridium perfringens with different toxins

There are five types (A-E) of C. perfringens, which can be identified through their toxin production (see table 1). All strains produce alpha-toxin. Furthermore, Clostridium perfringens has been described to produce eight other toxins, three (delta, theta, kappa) can be lethal, but these are seldom involved in disease origin³⁷.

Table 1. Different types of Clostridium perfringens

High resilience gives an advantage against competitors

Since Clostridium perfringens is a spore-forming bacterium, it is very resilient to high temperatures, slight pH variations, and toxic chemicals^{43, 7}.

Labbe et al.³⁰ established that C. perfringens can reproduce at temperatures between 15-50 °C. Hence, proper refrigeration temperatures (below 10 °C) can be an effective means of control. The optimum range is between 37-47 °C, and at these temperatures, the mean generation time – the time required for the bacterial count to double – is approximately 10-12 minutes⁴¹. These short generation times allow the bacteria to outcompete other microorganisms that may need similar resources in a certain environment.

The optimum pH range of Clostridium perfringens is between 5.5-7.0²². However, it can grow at a pH as low as 5 and as high as 9. In live broiler chickens, the pH in the small intestine has been determined to be between 6.00-7.78.

Necrotic enteritis in poultry

The disease necrotic enteritis was first described by Parish^{45, 46} in cockerels in England. Some of the symptoms include depression, reluctance to move, ruffled feathers, somnolence, diarrhea, loss of appetite, and anorexia²¹. Mortality ranges from 0-50% ⁶ have been reported in infected flocks. Since then, virtually every area that raises poultry has reported signs of necrotic enteritis.

Clostridium perfringens – How NE unravels

As already mentioned, 10⁴ colony-forming units (CFU)/g of broiler digesta¹⁰ are normal and can be found in healthy birds. C. perfringens becomes problematic when counts reach 10⁷-10⁸ CFU/g⁶.

Necrotic enteritis is caused by types A and C of Clostridium perfringens, but normally, predisposing factors “set the stage”^{24, 48}. This could be seen in an investigation where they wanted to create a model to reproduce NE in a laboratory setting. Researchers realized that inoculation of C. perfringens alone did not cause the disease found in the field⁴⁸. Therefore, it was assessed that certain cofactors must play a significant role in the pathogenicity of C. perfringens. Williams⁵⁷ reviewed concurrent infections of coccidiosis and necrotic enteritis in chickens (Figure 1). The copious interactions of these diseases with predisposing factors, control methods, sources of infection, and disease form is a testament to the complexity of this poultry industry matter.

Coccidiosis creates access

Shane et al.⁵³ noted that several authors had considered coccidiosis to be a predisposing factor for NE. They proceeded to describe the pathogenesis of Eimeria acervulina, one of the protozoa responsible for coccidiosis in poultry. When the oocysts are ingested, they quickly attach to the intestinal wall causing lesions where the protozoa reproduce numerous times. These are the lesions to which C. perfringens attaches.

What happens in the animal?

Long et al.³³ proposed the pathogenesis for NE: First, epithelial cells are vacuolated, and the epithelium lifts off the lamina propria, which is congested and edematous. These lesions can be caused by a combination of factors like toxin production and/or, as just mentioned, coccidiosis. Clostridium perfringens cells attach to the lamina propria, where they thrive. The tissue becomes necrotic as large numbers of heterophils, a type of phagocyte, flood the foci (sites of lesions).

A combination of disease-inducing factors such as bacteria proliferation, heterophil lysis, and villus’ necrosis seem to develop quickly. The inflammation zone then becomes riddled with mononuclear cells, cells containing lymphocytes, antigen-presenting cells, and eosinophilic-staining (proteinaceous) amorphous material. This necrotizing process moves from the tip of the villi to the crypt.

Chronic version

In chronic cases, villi may be found to have multiple cysts from recurrent necrosis. In birds that overcome the disease, injured epithelial cells are replaced by newly formed reticular structures. These new cells travel from the crypt to the tip of the villi and replace the old, damaged cells. The result is a short, flat villus with a reduced surface area for nutrient absorption^{44, 45, 34}. These morphologically altered villi are the necrotic lesions found in the field and some C. perfringens challenge trials (Figure 2).

Acute form

The acute form of NE results in enlarged lesions along the gut wall, and the epithelium becomes eroded and detached; consequently, a diphtheritic membrane is formed. This yellow, green, or brownish pseudo-membrane is called the “Turkish towel,” which describes the appearance of the friable, gas-filled, foul-smelling GI tract⁵⁷.

Subclinical form

Poultry producers are not only concerned with the acute form of NE. Recent studies have shown that the disease’s subclinical form can be as detrimental as the acute illness¹⁹. Lovland and co-workers³⁵ stated that this symptomless disease is often overlooked at the farm, and the effects are only noticed at the processing facility.

Subclinical NE (SNE) can cause cholangiohepatitis, a condition where the liver is enlarged with pale reticular patterns and sometimes small, pale foci. In the United Kingdom, it was estimated that 4% of broiler carcasses and 12% of livers are condemned at processing plants due to clostridial infection; thereby, reducing profit³⁶. Moreover, sparse lesions that may be found in a case of SNE may be enough to hinder growth performance; thus, resulting in an underproductive flock³⁹.

Feeding Against Necrotic Enteritis

It has been reported that diet formulation has the greatest impact on the prevalence of C. perfringens in chicken GI tracts⁶¹. The poultry industry formulates diets on a least-cost basis, which may become problematic if nutritionists do not take into consideration the pathological consequences that some ingredients may have in the GI tracts of chickens. Every feed ingredient has a specific purpose in the diet. For instance, cereal grains are fed for their energy concentration as well as fiber. Also, some grain and animal/plant meals are used for their protein content. Since these ingredients are obtained from different sources, they are highly variable in macro and micronutrients¹.

The diet provides the conditions for proliferation

There are multiple elements that affect the proliferation of C. perfringens in chicken intestines, one of the most critical factors being diet formulation^{5, 36}. Some feed ingredients have been found to exacerbate the numbers of C. perfringens in chickens’ gastrointestinal tract. Diets formulated with wheat increased NE intestinal lesion scores compared to broiler chickens fed a corn-based diet⁴. In another study, Drew et al.¹⁰ investigated the effects of different protein sources on the intestinal populations of C. perfringens in broiler chickens. Diets were formulated to contain 230, 315, and 400 g/kg of fishmeal or soy protein concentrate (SPC). The numbers of C. perfringens in the ileum and ceca increased when the amount of protein increased from 230 to 400 g/kg.

Type of grain influences the occurrence of Clostridium perfringens

Authors have studied the effects of grain inclusion on gut microbiota, and it is well established that small cereal grains such as barley, rye, and wheat tend to increase the prevalence of C. perfringens in the GI tract. Shakouri et al.⁵² investigated the influence of barley, sorghum, wheat, and corn on counts of C. perfringens in the different intestinal segments. Corn and wheat had the lowest C. perfringens counts, followed by sorghum, while barley yielded the highest counts. These findings agree with Riddell and Kong⁵¹.

Other researchers have concluded that the increase in gut viscosity and increased chyme transit time elicit the overgrowth of C. perfringens in the intestines²⁸. Grains like wheat and barley contain high amounts of non-starch polysaccharides (NSP), which increase viscosity²⁶. Furthermore, it has been alleged that, since these grains are high in NSP, the bird cannot absorb nutrients as efficiently, thereby leaving them for microbes like C. perfringens to consume³¹.

Enzymes improve nutrient availability in the presence of C. perfringens

Shakori et al.⁵² and Jia et al.²⁶ also studied the impact of several diets with the inclusion of a blend of carbohydrases such as glucanase and xylanase. Their findings suggested that enzyme addition did not affect counts of C. perfringens in the different intestinal sections. However, they did find an improvement in growth performance. They stated that enzymes improved chyme viscosity by degrading the encapsulation of nutrients in diets.

For this reason, researchers have investigated the use of enzymes in wheat and barley-based diets on the incidence of C. perfringens in chicken intestines. Jackson et al.²⁵ studied the effect of beta-mannanase addition on flocks infected with Eimeria spp. and C. perfringens. They found that feeding this enzyme significantly reduced the impact of C. perfringens on the performance of infected flocks as well as intestinal lesion scores. Moreover, the authors explained that this might be due to beta-mannanase crossing the intestinal wall to provoke an immune response. They determined that this enzyme tended to ameliorate the symptoms of necrotic enteritis, but not significantly.

MOS may have a positive impact on immunity

Hofacre et al. ²³ found similar results when birds were fed mannan-oligosaccharides. A marked effect was only found when mannan-oligosaccharides were included along with lactic acid-producing, competitive exclusion products (probiotics).

The feed form is decisive

Feed form has also been investigated on the incidence of C. perfringens. When birds were fed whole wheat compared to ground, researchers found reduced counts of C. perfringens in the gut². These results can be extrapolated to the findings of Engberg et al.¹¹. They found that when birds were fed coarse versus fine mash or pellets, C. perfringens counts were consistently higher in flocks fed mash diets. These authors concluded that feeding pellets or whole grains increases gizzard activity, which consequently triggers hydrochloric acid production and decreases pH in the GI tract. This drop in pH of approximately 0.5 units may be responsible for decreased C. perfringens counts.

Mind the protein source

Another well-established fact is that the C. perfringens population can be affected by the type of the protein source and the inclusion rates.

Potato is worse than fish

Palliyeguru et al. ⁴² studied the inclusion of protein concentrates (potato, fish, and soy) on subclinical NE. They determined that the potato-containing diet resulted in the highest incidence of C. perfringens in the gut, followed by fish and soy. Also, the potato-containing diet had the highest activity of trypsin inhibitors and lowest lipid content. Increased trypsin inhibition does not allow for the inactivation of alpha and beta toxins produced by C. perfringens, resulting in increased intestinal wall lesions.

Fish is worse than soy due to the amino acid composition

Drew et al.¹⁰ formulated diets containing fishmeal or a soy protein concentrate at different levels. Feeding dietary fishmeal resulted in a higher incidence of C. perfringens as compared to the soy protein diet. Furthermore, with increasing levels of soy and fishmeal diets, counts of C. perfringens increased as well. A notable difference in fishmeal protein concentrate compared to the soy protein concentrate was the amino acid ratio in this experiment; the methionine and glycine ratios were 1.3 times greater in fishmeal diets. Muhammed et al.⁴⁰ determined that methionine was required for C. perfringens sporulation. This may be of interest to nutritionists since some authors have estimated that 10-20 % of synthetic amino acids are not absorbed and reach the lower intestinal tract, i.e., ceca; thereby, aiding in the proliferation of C. perfringens.

Fat source – animal fat is critical

The effects of fat sources on C. perfringens population remain largely unknown. Knarreborg et al.²⁹ studied the bacterial microflora in chicken intestines after feeding different dietary fats (soy oil and a tallow and lard mix) in rations containing antibiotic growth promoters (AGP). When soy oil was fed, C. perfringens counts were significantly lower than diets containing animal fats. The authors stated that, since plant oils contain higher amounts of unsaturated fatty acids, the chyme in birds fed oil diets would have decreased viscosity, decreasing transit time. Furthermore, an additive effect was found when soy oil was provided along with AGP, which may be due to facilitated antibiotic dispersion caused by the oil’s lipophilic properties. Knarreborg et al. (2002) investigated the effects of fat sources on C. perfringens. They found that total anaerobic counts increased with animal fat addition. However, zinc bacitracin was included in their diets, specifically targeting Gram-positive microorganisms like C. perfringens; thus, potentially biasing their results.

Antibiotics and coccidiostats in the diet – helpful, but finite

Antibiotics and coccidiostats have been commonly included in poultry diets since the mid-1940s and 1950s^{61, 58}.

Prescott et al.⁴⁹ studied the inclusion of zinc bacitracin to prevent necrotic enteritis and concluded that it successfully controlled the C. perfringens challenge. Flocks in the antibiotic treatments were able to overcome disease and perform similarly to unchallenged birds. Multiple authors have replicated these results using different antibiotics such as virginiamycin and salinomycin^{17, 3, 11}.

Improvements in flock performance with the inclusion of antibiotics and coccidiostats are well understood and omnipresent in the literature. However, the potential loss of subtherapeutic antibiotic usage in livestock in the United States due to increasing concerns over antimicrobial resistance and consumer demands makes research of viable alternatives to these compounds paramount.

So, what are your alternatives?

A lot of different approaches are possible. In general, these measures should act against Clostridium perfringens while supporting gut health.

Tested substances without the desired effects

Lastly, multiple options have been studied to control C. perfringens in poultry. Some researchers have studied the inclusion of complex carbohydrates and fibers like pine shavings, guar gum, and pectin with limited success^{4, 31}. Another popular alternative is the use of competitive exclusion-based products such as prebiotics and probiotics^{27, 16}. Still, these products failed to yield consistent results.

Other options that have been investigated are the addition of lactose and organic acids^{54, 38}. Potassium diformate did not produce lowered counts of C. perfringens. Lactose reduced C. perfringens counts but resulted in undesirable ceca characteristics including, enlargement and increased fermentation⁵⁴.

Essential oils alone or in combination may be a solution

Mitsch and coworkers³⁹ investigated the efficacy of two blends of essential oils with positive effects on the reduction of C. perfringens from the gut and feces of broilers. Gaucher and coworkers¹⁵ compared growth performance and gut health of broilers fed a conventional (anticoccidials and AGPs) vs. ABF (Coccidiosis vaccine and essential oil blends) diet. They established that livability, age at slaughter, and percentage of condemnation did not change with diet type. However, average daily weight gain and FCR were negatively affected. Furthermore, NE was more prevalent in ABF flocks.  Still, many authors agree that a multifactorial approach is necessary if antibiotics should be completely replaced by these strategies³⁶.

A contemporary study by Wati et al.⁵⁶ aimed to compare AGPs to a commercial blend of essential oils fed to broilers. Authors found that chickens fed essential oils had body weights and FCRs that were statistically similar to the AGP treatment. Moreover, both AGP and essential oil treatments had statistically lower counts of Salmonella and E. coli after an oral challenge than the control group.

Conclusion

C. perfringens is a potential pathogen found in every place poultry is raised. Therefore, we must continue to identify strategies to control the development of Necrotic Enteritis. Since antibiotics alone may not always successfully control C. perfringens and have the potential for subtherapeutic use loss in the US, a multifactorial approach must be considered and investigated. Grain size, enzymes, feed form, animal protein source, fats, and feed supplements such as essential oils can affect the proliferation of C. perfringens. Nutritionists, veterinarians, and live production personnel must come together to develop the best approach for their specific complex circumstances.

Figure 1. Interaction between coccidiosis and NE with environmental factors

Solid-line arrows are beneficial in controlling disease. Dashed-line arrows impart high disease risk factors. Double-line arrows depict major disease-risk factors. AGP, antibiotic growth promoter; CIA, chick infectious anemia; CEP, competitive exclusion product; Cp, Clostridium perfringens; IBD, infectious bursal disease; MD, Marek’s disease; NE, necrotic enteritis. (Williams, R.B. 2005)

 Figure 2. Necrotic Enteritis lesions in chicken intestines

Yellowish necrotic lesions in three intestinal samples. Intestines A and C show a few marked lesions. Intestine B shows clusters of lesions typical of the “Turkish towel” syndrome. (Source: http://www.mdpi.com/2072-6651/2/7/1913/htm. Accessed: January 14, 2021).

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by  Merideth Parke, Regional Technical Manager, EW Nutrition

To contain and reverse antimicrobial resistance, consumers and government regulators expect changes in pork production with the clear goal to reduce antibiotic use. For healthy, profitable pig production with simultaneous antibiotic reduction, a holistic strategy is required: refocusing human attitudes and habits, optimal pig health and welfare, and applying potential antibiotic alternatives.

Pig producers need to manage pathogenic pressure while reducing antibiotics

Intensive pig production has stress points associated with essential husbandry procedures such as weaning, health interventions, and dietary modifications. Stress is widely accepted to have a negative impact on immune system effectiveness, enhancing opportunities for pathogenic bacteria to invade at a local or systemic level. The gastrointestinal and respiratory systems are highly susceptible to developing disease as a result of these combined factors. Interventions such as antibiotics are commonly implemented to reduce the impact of pathogens and manage pig health. Processes that minimize the number of pathogens in the environment are the foundation for a successful antibiotic reduction plan. The challenge is to smartly combine strategies to keep the gastrointestinal and respiratory tract intact and robust.

Phytomolecules, the specific active defense compounds found in plants, have been identified as capable of enhancing pig health through antimicrobial (Cimanga et al., 2002, Franz et al., 2010), antioxidative (Katalinic et al., 2006, Damjanovic-Vratnica et al., 2007, Lee et al., 2011), digestion-stimulating and immune-supportive functions. As many thousands of phytomolecules exist,  laboratory research has focused on identifying those with the capability of microbial management, facilitating the end goal of reducing the reliance on antibiotics for pig health and welfare and the production of safe pork (Zhai et al., 2018).

Which roles can phytomolecules play in reducing antibiotics?

The gastrointestinal tract benefits from applying phytomolecules such as capsaicin, carvacrol, and cinnamaldehyde, as they:

• support a balanced and stable biome,
• prevent dysbiosis, maintain tight junction integrity (Liu et al., 2018),
• increase secretion of digestive enzymes, and
• enhance gut contractility (Zhai et al., 2018).

Pigs most susceptible and in need of phytomolecule gastrointestinal supportive actions are piglets at weaning and pigs of all ages undergoing stress, pathogen challenges, and/or dietary changes.

Porcine respiratory disease is a complex multifactorial disorder. It frequently requires antibiotics to manage infection pressure and clinical disease to maintain pig health, welfare, and production performance. Causal pathogens may be transmitted by direct contact between pigs in saliva (Murase et al., 2018) or bioaerosols (LeBel et al., 2019), via the nasal or oral cavities (inhalation directly into the airways and lungs), or via an unhealthy gut. Phytomolecules such as carvacrol and cinnamaldehyde have antimicrobial properties. Hence, they may help contain respiratory pathogens in their natural habitat (the upper respiratory tract) or during transit through the oronasal cavity and gastrointestinal tract (Swildens et al., 2004, Lee et al., 2001).

In addition to supporting the gastrointestinal and respiratory systems, phytomolecules such as menthol and 1,8-cineole have been shown to enhance the physical and adaptive immune systems in multiple species (Brown et al., 2017, Barbour et al., 2013). When applied via drinking water, adherence to the oronasal mucosa facilitates the inhalation of the active phytomolecule compounds into the respiratory tract. There, they act as mucolytics, muscle relaxants, and enhancers of the mucociliary clearance mechanism (Başer and Buchbauer, 2020). Phytomolecules have also been documented to positively influence the adaptive immune system, promoting both humoral and cell-mediated immune responses (Awaad et al., 2010, Gopi et al., 2014, Serafino et al., 2008).

How phytomolecules feature in the holistic approach to antibiotic reduction

Antibiotic reduction programs positively enact social responsibility by reducing the risk to farmworkers of exposure to antimicrobial-resistant bacteria. They also help maintain or increase efficiency in safe pork production – pork with minimal risk of antibiotic residues.

Implementation of a successful health program with reduced antibiotic use will require:

• application of strict internal and external biosecurity processes;
• evaluation and monitoring of AMR bacteria;
• partnerships with specialist nutritionists to target a lifetime healthy gut biome; and
• phytomolecule-assisted health management (Figure 1).

A combination of in vitro and in vivo studies provides evidence that specific phytomolecules can support both enteric and respiratory systems through biome stabilisation and pathogen management (Bajabai et al., 2020). Antimicrobial activity of thymol, carvacrol, and cinnamaldehyde has been reported against respiratory pathogens including S. suis, A. pleuropneumoniae, and H. parasuis (LeBel et al., 2019); multi-drug resistant and ESBL bacteria (Bozin et al., 2006); enteric pathogens including E. coli, Salmonella enteritidis, Salmonella cholerasuis, and Salmonella typhimurium (Penalver et al., 2005); Clostridium spp., E. coli spp., Brachyspira hyodysenteriae (Vande Maelle et al., 2015); and Lawsonia intracellularis (Draskovic et al., 2018). These results have shown phytomolecules to be effective antimicrobial alternatives for incorporation into holistic pig health programs.

Additionally, the inclusion of phytomolecules into pig production systems also enhances production performance by reducing the negative impact of stress on the pig and increasing the positive effects on gut health and nutrient utilization (Franz et al., 2010). Phytomolecules that directly impact digestive actions include capsaicin, which optimizes the production of digestive enzymes and increases serotonin for gut contraction maintenance and improved digesta mixing (Zhai et al., 2018). Cineol’s antioxidative activities provide support during times of stress (Cimanga et al., 2002).

Phytomolecules are key to reducing antibiotics in pig production

The pig industry searches for alternatives to therapeutic, prophylactic, and growth-promoting antibiotic applications to keep available antibiotics effective for longer – and to address the social responsibility of mitigating AMR. This search for ways to produce safe pork has made it clear that only a combination of management and antibiotic alternatives can achieve these aligned goals.

Biosecurity, hygiene, stress reduction, and husbandry and nutritional advances form the foundation for the strategic application of specific phytomolecules (Zeng et al. 2016). Supporting pig production and health, this complete holistic solution (EIP-AGRI) moves the pig industry into a future where antibiotic reduction or removal, with equivalent or increased production of safe pork, becomes a reality.

References

Awaard M, Abdel-Alim G, Sayed K, Kawkab, Ahmed1 A, Nada A , Metwalli A, Alkhalaf A. “Immunostimulant effects of essential oils of peppermint and eucalyptus in chickens”. Pakistan Veterinary Journal (2010). 2:61-66. http://www.pvj.com.pk/

Bajagai YS, Alsemgeest J, Moore RJ, Van TTH, Stanley D. “Phytogenic products, used as alternatives to antibiotic growth promoters, modify the intestinal microbiota derived from a range of production systems: an in vitro model”. Applied Microbiology and Biotechnology (2020). 104:10631-10640. https://doi.org/10.1007/s00253-020-10998-x

Barbour EK, Shaib H, Azhar E, Kumosani T, Iyer A, Harakey S, Damanhouri G, Chaudary A, Bragg RR. “Modulation by essential oil of vaccine response and production improvement in chicken challenged with velogenic Newcastle disease virus”. Journal of Applied Microbiology (2013). 115, 1278-1286. https://doi:10.1111/jam.12334

Biljana Damjanovic-Vratnica, Tatjana Dakov, Danijela Sukovic, Jovanka Damjanovic. “Antimicrobial effect of essential oil isolated from Eucalyptus globulus Labill” (2011). Czech Journal of Food Science 27(3):277-284. https://www.agriculturejournals.cz/publicFiles/39925.pdf

Bozin B, Mimica-Dukic N, Smin N, Anackov G. “Characterization of the volatile composition of essential oils of some Lamiaceae spices and the antimicrobial and antioxidant activities of the entire oils” Journal of Agriculture and Food Chemicals (2006). 54:1822-1828 https://pubs.acs.org/doi/10.1021/jf051922u

Brown SK, Garver WS, Orlando RA. “1,8-cineole: An Underappreciated Anti-inflammatory Therpeutic” Journal of Biomolecular Research &Therapeutics (2017). 6:1 1-6  https://doi: 10.4172/2167-7956.1000154

Cimanga K., Kambu K., Tona L., Apers S., De Bruyne T., Hermans N., Totte J., Pieters L., Vlietinck A.J. “Correlation between chemical composition and antibacterial activity of essential oils of some aromatic medicinal plants growing in the Democratic Republic of Congo”. Journal of Ethnopharmacology (2002) 79: 213–220. https://doi.org/10.1016/s0378-8741(01)00384-1

Draskovic V, Bosnjak-Neumuller J, Vasiljevic M, Petrujkic B, Aleksic N, Kukolj V, Stanimirovic Z. “Influence of phytogenic feed additive on Lawsonia intracellularis infection in pigs” Preventative Veterinary Medicine (2018). 151: 46-51 https://doi.org/10.1016/j.prevetmed.2018.01.002

European Innovation Partnership Agricultural Productivity and Sustainability (EIP-AGRI). https://ec.europa.eu/eip/agriculture/en/european-innovation-partnership-agricultural

Franz C., Baser KHC, Windisch W. “Essential oils and aromatic plants in animal feeding-a European perspective. A review Flavour”. Flavour and Fragrance Journal (2010) 25:327-40. https://doi.org/10.1002/ffj.1967

Gopi M, Karthik K, Manjunathachar H, Tamilmahan P, Kesavan M, Dashprakash M, Balaraju B, Purushothaman M. “Essential oils as a feed additive in poultry nutrition”. Advances in  Animal and Veterinary Sciences (2014) 1:17.  https://doi.10.14737/journal.aavs/2014.2.1.1.7

Başer, Kemal Hüsnü Can, and Gerhard Buchbauer. Handbook of Essential Oils Science, Technology, and Applications. Boca Raton: CRC Press, 2020.

Hengziao Zhai, Hong Liu, Shikui Wang, Jinlong Wu, Anna-Maria Kluenter. “Potential of essential oils for poultry and pigs.” Animal Nutrition 4 (2018): 179-186.  https://doi.org/10.1016/j.aninu.2018.01.005

Katalinic V., Milos M., Kulisic T., Jukic M. “Screening of 70 medicinal plant extracts for antioxidant capacity and total phenols”. Food Chemistry (2006) 94(4):550-557.  https://doi.org/10.1016/j.foodchem.2004.12.004

LeBel G., Vaillancourt K., Bercier P., Grenier D. “Antibacterial activity against porcine respiratory bacterial pathogens and in vitro biocompatibility of essential oils”. Archives of Microbiology (2019) 201:833-840; https://doi.org/10.1007/s00203-019-01655-7

Lee KG, Shibamoto T. “Antioxidant activities of volatile components isolated from Eucalyptus species”. Journal of the Science of Food and Agriculture (2001). 81:1573-1597. https://doi.org/10.1002/jsfa.980

Liu SD, Song MH, Yun W, Lee JH, Lee CH, Kwak WG Han NS, Kim HB, Cho JH. “Effects of oral administration of different dosages of carvacrol essential oils on intestinal barrier function in broilers” Journal of Animal Physiology and Animal Production (2018) https://doi.org/10.1111/jpn.12944

Murase K, Watanabe T, Arai S, Kim H, Tohya M, Ishida-Kuroki K, Vo T, Nguyen T, Nakagawa I, Osawa R, Nguyen N, Sekizaki T. “Characterization of pig saliva as the major natural habitat of Streptococcus suis by analyzing oral, fecal, vaginal, and environmental microbiota”. PLoS ONE (2019). 14(4). https://doi.org/10.1371/journal.pone.0215983

Nethmap MARAN report 2018. https://www.wur.nl/upload_mm/7/b/0/5e568649-c674-420e-a2ca-acc8ca56f016_Maran%202018.pdf

Penalver P, Huerta B, Borge C, Astorga R, Romero R, Perea A. “Antimicrobial activity of 5 essential oils against origin strains of the Enterobacteriaceae family”. Acta Pathologica Microbiologica, et Immunologica Scandinavica (2005) 113:1-6. AromaticScience, LLC Antimicrobial activity of five essential oils against origin strains of the Enterobacteriaceae family.

Serafino A, Vallebona PS, Adnreola F, Zonfrillo M, Mercuri L, Federici M, Rasi G, Garaci E, Pierimarchi P. “Stimulatory effect of Eucalyptus essential oil on innate cell-mediated immune response” BioMed Central (2008). 9:17 https//:doi:10.1186/1471-2172-9-17

Swildens B, Stockhofe-Zurwieden N, van der Meulen J, Wisselink HJ, Nielen M. “Intestinal translocation of Streptococcus suis type 2 EF+ in pigs”. Veterinary Microbiology (2004) 103:29-33. https://doi: 10.1016/j.vetmic.2004.06.010

Vande Maele L, Heyndrickx M, Maes D, De Pauw N, Mahu M, Verlinden M, Haesbrouck F, Martel A, Pasmans F, Boyen F. “In vitro susceptibility of Brachyspira hyodysenteriae to organic acids and essential oil components”. Journal of Veterinary Medical Science (2016). 78(2):325-328.  https://doi.org/10/1292/jvms.15-0341

Zeng Z, Zhang S, Wang H, Piao X. “Essential oil and aromatic plants as feed additives in non-ruminant nutrition: a review”. Journal of Animal Science and Biotechnology (2015) 6:7. https://doi.org?10/1186/s40104-015-004-5

Strong demand by consumers; restaurant chains and wholesalers for antibiotic-free (ABF) meat; the threat of antimicrobial resistance; and stringent regulations on the use of antibiotics – there are many good reasons for poultry producers to strive for antibiotic-free production systems. Crucially, to successfully produce poultry meat without antibiotics requires a paradigm shift that starts right at the parent stock level, with the antibiotic-free production of hatching eggs.

Broiler breeders’ gut health is linked to progeny’s performance

Broiler breeders’ performance is measured in terms of how many saleable day old chicks (DOCs) per hen they produce. However, within a sustainable ABF production system (also known as No Antibiotics Ever or NAE), this parameter is not seen in isolation. Breeder hens’ nutritional and health status not only affect the number of DOCs they can produce, but also the transfer of nutrients, antibodies, microbiota and even contaminants, e.g. mycotoxins, to the egg – and therefore, their progeny’s long-term health and performance.

This starts with egg formation, which requires several metabolic processes in the hen to function perfectly. If the hen’s intestinal integrity is compromised, for example due to mycotoxins, she will absorb fewer nutrients, which in turn affects egg formation. Mycotoxicosis has particularly insidious effects for egg formation as it can damage the liver whose biosynthetic activities strongly impact on the egg’s internal (yolk) and external (eggshell) quality.

Chick embryos depend on the maternal antibodies and nutrients deposited in the yolk, including vitamin D3, carotenoids, and fatty acids, to develop normally. Eggshell quality, among other things, affects the embryo’s access to oxygen, which is especially important when it develops body tissues.

Hens’ ability to form healthy eggs depends on their diet and health. Research indicates that, via the impact on egg formation, broiler breeders’ feeding program quantifiably influences their progeny’s immune system and intestinal health. There is indeed a direct relationship between parent and offspring’s gut health because the chick’s microbiome is in part also inherited from the hen. The impact on DOC quality is thus one of many dimensions to consider when calibrating one’s broiler breeders feeding approach.

The challenge of feeding an ABF broiler breeder

Just as their offspring, breeder hens are genetically predisposed for rapid growth and muscle development. From rearing right through to the laying period, poultry nutritionists need to carefully balance their diets and moderate weight gain in order for hens to reach their reproductive potential.

Different stages of a breeder’s life cycle come with different objectives – for example, good flock uniformity in the rearing period versus egg size and hatchability in the laying phase – and thus different requirements in terms of calories, amino acids, vitamins, and minerals. What remains constant is that the actual nutrient intake depends on intestinal health, determining both the breeders’ performance and, via the impact on egg characteristics, its progeny’s performance.

The feeding regimes adopted to avoid hens becoming overweight can have a negative effect on their gut flora. Without antibiotics as a tool to maintain or recover optimal gut function, even mild intestinal disorders can quickly become chronical impairments that negatively impact breeders’ productivity. In ABF production systems, intestinal health therefore needs to be a central focus for the feeding strategy.

Can phytomolecules improve broiler breeders’ performance?

Among the plethora of feed additives, phytomolecules, or secondary plant compounds, stand out as a class of active ingredients that may help to improve gut health and thereby reduce the use of antibiotics.  Synthesized by plants as a defense mechanism against pathogens, phytomolecules combine digestive, antimicrobial and antioxidant properties.

Some studies have shown that phytomolecules-based products can increase broilers’ body weight gain and improve laying hens’ laying rate, egg mass and egg weight. Both broilers and laying hens responded to the inclusion of phytomolecules in their diet with inclusion rate-dependent improvements in feed conversion. To evaluate if phytomolecules could similarly improve broiler breeders’ performance, two trials were conducted.

Study I: Effect of phytomolecules on laying performance during peak production

The first study was set up on a farm in Thailand. In total, 40000 Cobb broiler breeders (85% female, 15% male) were divided into two groups with 8500 hens (one house) in the control and 25500 (three houses) in the trial group. Both groups were fed standard feed. The trial group additionally received a phytomolecules-based liquid complementary feed (Activo® Liquid, EW Nutrition GmbH) via the waterline from week 24 to week 32 at a rate of 200ml/1000L during 5 days per week.

Activo® Liquid was found to have a positive influence on laying performance (Figure 1). The average laying rate increased by 7.2% during the trial period, resulting in almost 3 additional hatching eggs per hen housed. A further indication of the beneficial influence that this particular combination of phytomolecules had on gut health was a 0.2% lower mortality.

Figure 1: Laying rate (%) of breeder hens during first 9 weeks of production

Study II: Effect of phytomolecules on laying performance after peak production

For a second study, conducted in the Czech Republic, 800 female and 80 male Hubbard breeders (JA57 and M77, respectively) were divided into 2 groups with 5 replicate pens and 80 female and 8 male breeders per pen. The experiment started after the peak-production period, at 34 weeks of age and ended at 62 weeks of age. All animals received a standard mash diet. For one group a phytogenic premix (Activo^®, EW Nutrition GmbH) was added to the diet at a rate of 100g/MT.

The results indicate that Activo^® helped maintain the breeder hens’ egg laying performance close to the breed’s genetic potential (Figure 2). In the course of the experiment, Activo® supplemented birds produced 3.6 more eggs than control birds, while consuming a similar amount of feed. As a result, feed consumption per egg produced was lower for birds receiving phytomolecules than for the control birds (169.9 versus 173.6g/d, respectively).

As hatchability was not influenced by the dietary treatment in this study (P>0.5), the 3.6 extra eggs resulted in 2.9 extra day old chicks per hen produced, during the post-peak period alone.
The microencapsulated, selected phytomolecules contained in Activo^® are likely to have improved gut health and feed digestibility, and thereby enhanced the animals’ feed efficiency.

Figure 2: Laying rate (%) of breeder hens week 35 till 62

Chicken or egg? Antibiotic-free poultry production looks at the bigger picture

To successfully produce antibiotic-free poultry meat requires a systematic re-think of each component of the production process. Broiler breeders’ lay the foundation for their progeny’s health and performance via the egg. Breeder hens need to be in optimal health to consistently deliver optimal eggs. Without recourse to antibiotics for maintaining or recovering intestinal functionality, an effective ABF production needs to make gut health central to its feeding approach.

The trials reviewed demonstrate that selected phytomolecules quantifiably boost breeders’ laying performance, increasing the number of hatching eggs and DOCs, while reducing mortality and feed consumption per egg produced. As part of an intelligent antibiotic reduction strategy, the right phytogenic products can be potent tools to help poultry producers achieve their NAE objectives.

by S. Regragui Mazili, T. van Gerwe and M. Caballero

References

Calini, F., and F. Sirri. “Breeder Nutrition and Offspring Performance.” Revista Brasileira De Ciência Avícola 9, no. 2 (2007): 77-83. doi:10.1590/s1516-635×2007000200001.

Ding, Jinmei, Ronghua Dai, Lingyu Yang, Chuan He, Ke Xu, Shuyun Liu, Wenjing Zhao, et al. “Inheritance and Establishment of Gut Microbiota in Chickens.” Frontiers in Microbiology 8 (October 10, 2017): 1967.

Kuttappan, Vivek A., Eduardo A. Vicuña, Juan D. Latorre, Amanda D. Wolfenden, Guillermo I. Téllez, Billy M. Hargis, and Lisa R. Bielke. “Evaluation of Gastrointestinal Leakage in Multiple Enteric Inflammation Models in Chickens.” Frontiers in Veterinary Science 2 (December 14, 2015): 66.

Moraes, Vera M. B., Edgar O. Oviedo-Rondón, Nadja S. M. Leandro, Michael J. Wineland, Ramon D. Malheiros, and Pamela Eusebio-Balcazar. “Broiler Breeder Trace Mineral Nutrition and Feeding Practices on Embryo Progeny Development.” Avian Biology Research 4, no. 3 (2011): 122–32.

Oviedo-Rondon, Edgar O., Nadja S. M. Leandro, Rizwana Ali, Matthew Koci, Vera M. B. Moraes, and John Brake. “Broiler Breeder Feeding Programs and Trace Minerals on Maternal Antibody Transfer and Broiler Humoral Immune response1.” The Journal of Applied Poultry Research 22, no. 3 (October 1, 2013): 499–510.

What we know about S. suis epidemiology and pathogenesis

Practically all farms worldwide have carrier animals, but the percentage of animals colonized “intra-farm” varies between 40 and 80%, depending on several factors such as environmental conditions, hygiene measures, and the virulence of the S. suis strains involved.

How S. suis strains are classified

S. suis strains were once classified into 35 serotypes, according to their different capsular polysaccharides(CPS), theoutermost layer of the bacterial cell. Due to phylogenic and genomic sequencing, some of the old serotypes (20, 22, 26, 32, 33, and 34) are now reclassified, either in other bacterial genera or in other Streptococcus species. This has reduced the total to 29 S. suis serotypes.

Globally, the prevalence of the disease varies between 3% and 30%. The main serotypes affecting pig population are type 2 (28%), 9 (20%), and 3 (16%); differences in the geographical distribution are shown in Figure 1.

Figure 1: Global distribution of S. suis serotypes
Based on different sources, incl. Goyette-Desjardins et al. (2014), Zimmermann et al. (2019), and Gebhart (2019)

In addition to the serotype classification based on CPS antigens, S. suis has also been genetically differentiated into “sequence types” using the MLST (Multi Locus Sequence Typing) technique. The distribution of both porcine and human sequence types is detailed in Figure 2.

Figure 2: S. suis sequence types and their worldwide distribution

How S. suis is transmitted in swine

The main transmission routes are, firstly, the vertical sow-piglet route; the mucosa of the vagina is the first point of contamination. In the farrowing room, respiratory transmission from the sow to the piglets takes place. Horizontal transmission between piglets has also been proven to occur, especially during outbreaks in the post-weaning phase. This form of transmission happens through aerosols, feces, and saliva.

While in humans, the possibility of infection via the digestive tract has been confirmed, there are discussions about this route for swine. De Greeff et al. (2020) argue, based on in vitro and in vivo data, that infection through the digestive tract is associated with specific serotypes. Serotype 9, for example, would have a greater capacity for colonizing the gastrointestinal tract, and from there, the bacteria’s translocation takes place. The same authors point out that, in Western Europe, S. suis serotype 9 has become one of the most prevalent serotypes in recent years.

How S. suis colonization occurs

Although there are still unknown mechanisms in the pathogenesis of the disease, it can be schematically summarized how colonization occurs (Figure 3). From the different infection routes, the pathogen always passes through the mucosa. When S. suis enter the bloodstream, it can lead to a systemic infection, ending in septicemia, meningitis, endocarditis, or pneumonia, or a local infection at the joints level, causing arthritis.

According to Haas and Grenier (2018), different pathogenicity factors intervene in each of the processes. The CPS, for example, are relevant during colonization and the initial progression (indicated by black arrows). Microvesicles released by S. suis cell membranes are more involved in the passage to the bloodstream or, for example, the progression towards local or systemic infection (indicated by white arrows).

Figure 3: Pathogenesis of S. suis infection
Source: based on Haas and Grenier (2018)

Depending on the host and the immune response, the well-known clinical signs of the disease will occur. Although they may begin in the lactation phase, the highest prevalence of meningitis (the main clinical symptom) usually occurs between the 5th and the 10th week of life, that is, between two and three weeks after weaning.

How to diagnose S. suis infection

Diagnosing S. suis is relatively simple at a clinical level; however, we need to know how to differentiate it from G. parasuis in the case of animals with nervous symptoms. We also need to distinguish S. suis from other pathogens responsible for producing arthritis, such as M. hyosynoviae or the fibrin-producing agent M. hyorhinis.

Laboratory techniques are developing on two fronts. Among molecular techniques, multilocus sequence typing (MLST) is considered the gold standard for serotyping. It is still costly and not yet practicable for large samples at the farm level. In contrast, several types of polymerase chain reaction (PCR) show greater practical applicability. Quantitative PCRs (qPCR) are used for the evaluation of bacterial load, and some PCRs are based on the identification of specific virulence genes.

Due to the relevance of S. suis for human health, more complex techniques are also available, such as the complete sequencing of the bacterial genome. This type of method aims to develop epidemiological analyzes together with the differentiation between virulent and non-virulent S. suis strains. Research is also underway in serology, particularly on evaluating maternal immunity and its interference with the piglet, as well as autogenous vaccines monitoring.

Why S. suis sometimes causes disease: Virulence factors and coinfections

Streptococcus suis is a pathobiont, i.e., a microorganism that belongs to the commensal flora of animals but generates disease under certain conditions. In their daily work on farms, clinical veterinarians, for instance, find that S. suis often colonizes the upper respiratory tract, nasal cavity, and tonsils without causing disease. S. suis pathogenicity is associated with an astounding range of different circumstances or triggering factors; some sources list more than 100 virulence factors. Several factors are considered essential in the development of pathogenesis; others, however, are the subject of ongoing research (cf. Xia et al., 2019, and Segura et al., 2017).

Critical virulence factors

• One of the most important proteins is the CPS that establishes serotypes. The CPS largely determines the bacteria’s adhesion and colonization behavior. It can modify its thickness depending on the stage: it becomes thinner when adhering to the mucociliary apparatus and thicker when circulating through the bloodstream, protecting the bacteria against possible attacks by immune system cells.
• Likewise, suis has an adhesin known as Protection Factor H (FHB) that protects it from phagocytosis by macrophages and can also interfere with the complement activation pathways of the immune system.
• Suilysin is one of the most critical suis‘ protein toxins. This toxin plays a fundamental role in the interaction with host cells (modulating them to facilitate invasion and replication within the host cells) as well as in the inflammatory response.
• S. suis is a mucosal pathogen and, hence, triggers a mucosal immunity response, mainly by immunoglobulins A (IgA). S. suis has developed proteases capable of destroying both IgA and IgG.
• Research is still in progress, but both suis serotype 2 and 9 encode the development of adhesion proteins that facilitate mucociliary colonization when salivary glycoproteins are present (these are called antigens 1 and 2).
• Other than Suilysin, two of the bacteria’s protein components that have been studied in-depth to develop subunit vaccines are the MRP (Muramidase Release Protein) and EF (Extracellular Factor) protein. Whether the expression of these proteins is associated with virulence depends on the serotype.
• Recent research indicates that greater biofilm production capacity is associated with the more virulent suis strains. The production of biofilm is closely related to the production of fibrinogen, which allows the bacteria to develop resistance to the action of antimicrobials, to colonize tissues, to evade the immune system, etc.

Concomitant factors for S. suis infection

Even though S. suis is a primary pathogen that can cause disease by itself, many factors can exert a direct or indirect influence on whether or not and to which extent disease develops.

Veterinarians and producers are well aware of the influence of environmental and management factors such as temperature variations, poor ventilation together with poor air quality, irritants for the respiratory tract, as well as correct densities for animals’ welfare. Occasionally, depending on the geographical location, S. suis can be considered as a seasonal pathogen, showing a higher prevalence during the coldest months of the year when ventilation is lower or not well-controlled.

At the level of the individual animal, concomitant pathogens, environmental changes, diet changes, previous pathologies, piglet handling problems, etc., all come into play. Younger piglets tend to be more susceptible because of the decrease in maternal immunity or insufficient colostrum intake; diarrhea during the lactation phase also increases disease vulnerability.

Recently, researchers have started to explore the hypothesis that a change in the digestive tract microbiome balance may favor a pathogenic trajectory. Some results indicate that changes in the microbiota around the moment of weaning could indeed trigger disease. I will return to the vital topic of the digestive tract in S. suis pathogenesis below.

The role of coinfections

The virulence of S. suis can increase in the presence of other pathogens, both viral and bacterial. Among the main viruses, key interactants are the PRRS virus, the influenza virus (SIV), as well as Porcine Circovirus (PCV) and Porcine Respiratory Coronavirus (PRCV). At the bacterial level, Bordetella bronchiseptica and Glaesserella parasuis have the most direct interaction with S. suis (Brockmeier, 2020).

There are several mechanisms by which coinfections might increase S. suis virulence: some of them (i.e., B. bronchiseptica and SIV) alter the epithelial barrier, facilitating the translocation of S. suis. Moreover, viruses such as PRRS either cause an alteration in the response of the immune system or destroy relevant immune system cells.

Valentin-Weigand et al. (2020) posit that the influenza virus increases the pathogenic capacity of S. suis so that, for specific strains, the disease can develop even in the absence of the key virulence factor suilysin. This highlights the importance of controlling coinfections for successful S. suis management.

The five pillars of holistic S. suis management in swine

The challenge of managing this problematic pathogen with limited use of antibiotics prompts a review of all strategies within our reach. From birth to slaughterhouse, interventions must be coordinated and cannot work independently.

1. Biosecurity

The principles of biosecurity are easily understood. Yet, across different locations and production systems, farms struggle with consistently executing biosecurity protocols. For the moment, it appears unrealistic to avoid the introduction of new S. suis strains altogether. Also, complete eradication is not feasible with the currently available tools.

Genetic companies and research centers will likely continue to explore how to reduce bacterial colonization in animals, to produce piglets that have no or only minimal S. suis populations. Again, this option is not available for now.

At the farm level, the most promising and feasible approach is to reduce the risk of bacterial transmission, i.e., to optimize internal biosecurity. This extends to controlling both viral and bacterial coinfections. The two major viruses affecting the nursery stage are the PRRS virus and Swine Influenza virus. Bacteria that can contribute to the disintegration of the mucosa, both at the respiratory level and the digestive level, are Atrophic Rhinitis (progressive or not) and digestive pathogens such as E. coli, Rotavirus and Eimeria suis. All possible measures to reduce the prevalence and spread of these co-infectants must be executed to help control S. suis.

2. The pre-weaning period

We need to consider several elements in the first hours after birth that influence the spread of the bacteria in the farrowing rooms:

• How is the colostrum distribution between the litters and the subsequent distribution of the piglets carried out?
• How is the “processing” of the piglets carried out after farrowing: iron administration, wound management, and tail docking?
• Are we taking any measure to prevent iatrogenic transmission of pathogens through needle exchange?

Until today, it is common practice to administer systemic (in-feed) or local (vaginally applied) antibiotics during the pre-weaning phase, albeit with partial or inconsistent successes in terms of reducing infection pressure. Notably, during the pre-weaning phase, the development of the piglet’s microbiota begins to take shape, and the systematic and prophylactic application of antibiotics in young animals can reduce bacterial diversity of the microbiome (Correa-Fiz et al., 2019). This, in turn, leads to a proliferation of bacteria with a pathogenic profile that could detrimentally influence subsequent pathology.

S. suis is an ultra-early colonizer; piglets can get infected already at birth

3. The post-weaning period

The post-weaning period undoubtedly constitutes the most critical stage of the piglets’ first weeks of life. In addition to social and nutritional stress, piglets are exposed to new pathogens. While maternal immunity is decreasing, piglets have not developed innate immunity yet; they are now most susceptible to the horizontal transmission of diseases. Hence, S. suis prevention during this phase center on measures that improve piglet quality. Key parameters include:

• Do we have a correct and homogeneous weight/age ratio at weaning?
• What is the level of anorexia in piglets? Do we practice suitable corrective measures to encourage the consumption of post-weaning feed?
• How are we feeding them? What medications do they routinely receive?
• How are housing facilities set up concerning density, environment, and hygiene?

Again, gut health is critical: Ferrando and Schultsz (2016) suggest that the status of the piglet’s weaning gastrointestinal tract centrally influences the subsequent development of the disease. Their research supports the idea that some specific S. suis serotypes can develop their pathogenesis from the digestive tract, just as in human medicine. While in humans, this digestive route is associated with the consumption of raw or insufficiently processed pork, in swine, the most susceptible moments are sudden changes in diet. The transition from milk to solid feed, in particular, leads to an increase in alpha-glucans that favor bacteria proliferation. Likewise, an increase in susceptibility occurs when the integrity of the intestinal wall is lost, for example, due to viral and bacterial coinfections.

4. Treatments and vaccination

Since weaning is such a difficult phase for the life of the piglet, it is a common practice on farms across the world to include one or several antibiotics in the post-weaning phase. Sometimes, when the legal framework allows, producers use a systematic antibiotic (i.e., beta-lactams or tetracyclines) and another one with a digestive profile (e.g., pharmacological doses of ZnO, trimethoprim, sulfa drugs and derivatives).

While antibiotics, for the most part, effectively prevent infection in the post-weaning phase, they can have adverse effects on the digestive tract. According to Zeineldin, Aldrige, and Lowe (2019), continued antibiotics use:

• might increase the susceptibility to other infections because of the imbalance of the microbiome,
• the immune system might be weakened, together with an alteration in metabolism,
• and it fosters a greater accumulation of bacteria that are resistant to antibiotics.

The effectiveness of curative antibiotics treatments varies considerably. In any case, early detection is critical; affected animals need to be isolated and provided with a comfortable environment. Therapeutic parenteral antibiotics are best combined with high-dose corticosteroids. Some sick animals are unable to stand or walk. As a complementary measure, it is recommended, where possible, to help them ingest some feed and water.

Much research attention is focused on finding suitable vaccines to control the disease. This is a challenging task: S. suis shows high genetic diversity, making the identification of common proteins difficult, and is protected against antibody binding by a sugar-based envelope. The research group around Mariela Segura and Marcelo Gottschalk, for example, is working on a subunit vaccine strategy that addresses both dimensions. Recently, Arenas et al. (2019) identified infection-site specific patterns of S. suis gene expression, which could serve as a target for future vaccines.

The arrival of a universal, affordable S. suis vaccine is still a distant hope, though. Inactivated vaccines generally offer low levels of antibodies at the mucosal level and would need some adjuvant to increase them. A multiple injection protocol will not work from a commercial and practical point of view. On the other hand, live attenuated vaccines risk re-developing virulence with potentially drastic effects on human health. To complicate the topic of vaccination further, there is a controversy regarding the time of application and what animals we should vaccinate – sows, piglets, both?

Today, though with variable results, the alternative to scarce commercial vaccines is autogenous vaccines. These are based on the suspected serotype(s) present on a particular farm. This strategy hinges on the difficult procedure of isolating the strain from the meninges, spleen, or joints of the animals. If this step is successful, a laboratory can then develop the autogenous vaccine. Immunization occurs mainly in piglets, but occasionally some sows are vaccinated during the lactation period.

5. Hygiene

Just as for any other pathogen, hygiene management is critical. The infection pressure can be lowered through simple steps, such as washing the breeders before they enter the farrowing room. It is, or it should be, standard practice to maximize hygiene in the processing of piglets, avoiding injuries or pinching of the gums during teeth cutting, as well as disinfecting the umbilical area.

We know that S. suis is usually very sensitive to most disinfectants, but that is can form a biofilm that allows it to withstand hostile conditions. Physical or chemical methods to eliminate biofilm-formation are thus vital for combatting S. suis effectively.

Figure 4: The 5 pillars of S. suis control and prevention

S. suis control and prevention: The future lies in the gut

There is no ideal solution for totally controlling S. suis yet: autogenous vaccines are only partially effective, and since we cannot continue to administer antibiotics systematically, it is necessary to look for alternatives. Pending the arrival of a universal vaccine, the most promising efforts focus on the gastrointestinal tract.

Microbiome balance to keep S. suis in check

The gastrointestinal tract is not only the site where nutrient absorption takes place.  The gut is the largest immune system organ in the body and most exposed to different antigens; therefore, what happens at the digestive level has a considerable influence on the immune system, locally and systemically.

The microbiome can be defined as the set of autochthonous bacteria that reside in the digestive system of animals. This group of bacteria is continually evolving and changes at critical moments in the life of animals. Simply put, a healthy microbiome is one that has a high bacterial diversity in the digestive tract (alpha diversity). The diversity between animals, on the other hand, should be low (beta diversity). A healthy microbiota implies the absence of dysbiosis and pathogens. Finally, one wants to promote the presence of bacteria that can produce substances with a bactericidal effect, such as short-chain fatty acids or bacteriocins.

Can we influence the microbiome to have fewer S. suis problems? Research by Wells, Aragon, and Bessems (2019) compared microbiota samples of the palatine tonsils from healthy and infected animals. They found that animals that would later develop the disease showed less diversity and, in particular, a diminished presence of the genus Moxarella. Importantly, they found that these differences in the microbiome’s composition of animals that later developed the disease were noticeable before weaning and at least two weeks before the outbreak occurred.

The same authors investigated in more depth, which bacteria in the microbiome were able to maintain homeostasis at the digestive level, finding that this was mostly the case for the genera Actinobacillus, Streptocuccus, and Moraxella. Moreover, they found that Prevotellacea and Rhotia produce antibacterial substances against S. suis.

Nutrition can impact the microbiome through targeted ingredients

We have to think about the microbiome of locations other than the digestive system as well. As we previously saw, the bacteria are transmitted through the mucosal route in the vagina, through the respiratory route, and there are recent studies that consider saliva as a leading source of infection in oral transmission.

This research contributes insights into how we might approach S. suis management through nutritional strategies. The question for nutritionists is, can you formulate feed that reduces the availability of S. suis’ favorite nutrients? S. suis appears to develop best when the feed contains large quantities of carbohydrates or starches. Other nutritional factors include the feed’s buffering capacity and the stomach pH of the piglets.

In times of antimicrobial resistance, additives are crucial for S. suis control and prevention

Gut health and nutrition approaches come together in the area of additives: targeted gut health-enhancing additives to feed or water will become a cornerstone of S. suis control. What we want to see in such products are molecules or substances that are capable of limiting, inhibiting, or slowing down the growth of S. suis by altering the membrane or interfering with the energy mechanisms of the bacteria.

There are already several products on the market with different active ingredients, such as phytomolecules, medium-chain fatty acids, organic acids, prebiotics, probiotics, etc. Soon, those products or combinations of them will be a part of our strategy for controlling this pathogen of such importance to our industry.

By Technical Team, EW Nutrition

References

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Lower use of antimicrobials with higher biosecurity

Studies and assessments such as those done by (Laanen, et al., 2013), (Gelaude, et al., 2014), (Postma, et al., 2016), (Collineau, et al., 2017) and (Collineau, et al., 2017a) relate a high farm biosecurity or improvements in biosecurity with lower antimicrobial use. Laanen, Postma, and Collineau studied the profile of swine farmers in different European countries, finding a relation between a high level of internal biosecurity, efficient control of infectious diseases, and a reduced need for antimicrobials.

Others such as Gelaude and Collineau studied the effect of interventions. The former examined Belgian broiler farms, finding a reduction of antimicrobial use by almost 30% when biosecurity and other farm issues were improved within a year. The latter studied swine farms located in Belgium, France, Germany and Sweden, in which antimicrobial use was also reduced in 47% across all farms and observed that farms with the higher biosecurity compliance and who also took a holistic approach, making other changes (e.g. management and nutrition), achieved a higher reduction in antimicrobial use.

Biosecurity interventions pay off

Of course, the interventions necessary to achieve an increased level of biosecurity carry some costs. However, the interventions, especially if taken with other measures such as improved management of new-born animals and nutritional improvements, also improve productivity. The same studies which report that biosecurity improvements decrease antimicrobial use also report an improvement in animal performance. In the case of broilers, Laanen (2013) found a reduction of 0.5 percentual points in mortality and one point in FCR; and Collineau (2017) obtained an improvement during both the pre-weaning and the fattening period of 0.7 and 0.9 percentual points, respectively.

Implementation, application and execution

Although biosecurity is considered the cheapest and most effective intervention in antibiotic reduction programmes, compliance is often low and difficult. The implementation, application, and execution of any biosecurity programme involve adopting a set of attitudes and behaviours to reduce the risk of entrance and spread of disease in all activities involving animal production or animal care. Measures should not be constraints but part of a process aimed at improving the health of animals and people, and a piece of the holistic approach to reduce antibiotics and improve performance.

Designing effective biosecurity programmes: Consider these 5 principles

When designing or evaluating biosecurity programmes, we can identify 5 principles that need to be applied. These principles set the ground for considering and evaluating biosecurity interventions:

1. Separation: Know your enemy, but don’t keep it close

It is vital to have a good separation between high and low-risk animals or areas on the farm, as well as dirty (general traffic) and clean (internal movements) areas on the farm. This avoids not only the entrance but the spread of disease, as possible sources of infection (e.g. wild birds) cannot reach the sensitive population.

2. Reduction: Weaken your enemy, so it doesn’t spread

The goal of the biosecurity measures is to keep infection pressure beneath the level which allows the natural immunity of the animals to cope with the infections, lowering the pressure of infection e.g. by an effective cleaning and disinfection programme, by the reduction of the stocking density, and by changing footwear when entering a production house.

3. Focus: Hunt the elephant in the room, shoo the butterflies

In each production unit, some pathogens can be identified as of high economic importance. For each of these, it is necessary to understand the likely routes of introduction into a farm and how it can spread within it. Taking into account that not all disease transmission routes are equally important, the design of the biosecurity programme should focus first on high-risk transmission routes, and only subsequently on the lower-risk transmission routes.

4. Repetition: Increasing the probability of infection

In addition to the probability of pathogen transmission via the different transmission routes, the frequency of occurrence of the transmission route is also highly significant when evaluating a risk (Alarcon, et al., 2013). When designing biosecurity programmes, risky actions such as veterinary visits, if repeated regularly must be considered with a higher risk.

5. Scaling: In the multitude, it is easy to disguise

The risks related to disease introduction and spread are much more important in big; more animals may be infected and maintain the infection cycle, also large flocks/herds increase the infection pressure and increase the risk by contact with external elements such as feed, visitors, etc.

Can we still improve our biosecurity?

Almost 100% of poultry and swine operations already have a nominal biosecurity programme, but not in all cases is it effective or completely effective. BioCheck UGent, a standardised biosecurity questionnaire applied worldwide, shows an average of 65% and 68% of conformity, from more than 1000 broiler and 2000 swine farms between respectively; opportunities to improve can be found in farms globally, and they pay off.

The bottom line

Biosecurity is necessary for disease prevention in any profitable animal production system. To make effective plans, these 5 principles should be applied to choose the right interventions that prevent the entrance and spread of disease. However, maintaining a successful production unit requires a holistic approach in which other aspects of biosecurity need to also be taken seriously, as well as actions to improve in other areas such as management, health and nutrition.

Authors: Marisabel Caballero, Global Technical Manager Poultry – EW Nutrition

References available under request.
Article published in Pig Progress.