Amongst naturally occurring mycotoxins, the five most important ones are aflatoxin, ochratoxin, deoxynivalenol, zearalenone, and fumonisin. Their incidence varies with the different climates, the prevalence of plant cultures, the occurrence of pests, and the handling of harvest and storage. Worldwide, farmers faced various and sometimes extremely high mycotoxin contamination in their feed materials in 2021. In the following, we show the major challenges in five main regions.

Asia faced high aflatoxin contamination

In Asia, high temperatures and humidity favor Aspergillus growth in grains. As a result, 95 % of the samples in South Asia and three-quarters of the samples in the China and the SEAP region (Indonesia, Philippines, Vietnam) showed aflatoxin contamination. The average contamination being higher than the threshold for all farm animals represents an increased risk for their health and performance.
In China and the SEAP region, also DON and T-2 were highly prevalent. Showing an incidence of more than 60%, they pose a severe risk when combined with aflatoxin.

Fumonisins afflicted the LATAM region

In Mexico, Central and South America, fumonisin contamination prevailed with an incidence of almost 90% at average levels that can be considered risky for swine and dairy. Together with incidence levels of around 60% found for DON and T2, fumonisin may act synergically in the animals, raising the risk for health and performance.
The Fusarium species linked to these mycotoxin contaminations occur in the grains on the field. Amongst others, insect damage, droughts during growing, and rain at silking favor their development.

Trichothecenes prevailed in North America

Contamination with trichothecenes (DON and T2) is the rule in the United States. The interaction of these mycotoxins is at least additive. The damage they cause to the gut opens the door to dysbiosis and disease, decreasing performance and profitability.
Also in this case, the responsible molds for the contamination are Fusarium species that develop when grains are in the field. As with fumonisins, the molds are favored by insect damage, moderate to warm temperatures and rainfall.

Fusarium toxins contaminated grain in the MEA region

Fusarium toxins such as Fumonisin, DON, and T2 prevail in the region of Egypt, Jordan, and South Africa. In combination, these mycotoxins have additive effects at the intestinal level, which increases the risk of dysbiosis in poultry.

A challenging year with long-term repercussions

Since mycotoxin contamination affects animal health, measures must be taken to provide the best protection. Besides improving agricultural practices in the field, smart in-feed solutions and mold inhibitors can be used in stored grain. These measures help producers preserve feed quality after a troubled year for crops around the world.

Factors for successful pig production

For years we have been increasing our understanding of how to formulate diets to support a healthy intestine through the optimal use of the supplied nutrients. Functional proteins, immune-related amino acids, and fiber are now applied worldwide for improved pig nutrition.

What lies beyond formulation adjustments?

However, pig producers have also realized that these nutritional strategies alone are not always fully efficient in preventing an “irritation” of the immune system and/or in preventing diseases from happening.

Immune nutrition is gaining a strong foothold in pig production, and the body of research and evidence grows richer every year. At the same time, we see genetics continually evolving and bringing production potential to increasingly higher levels. We are also constantly increasing our understanding of the importance of farm and feed management, as well as biosecurity in this process.

Finally, the importance of a stable microflora is now uncontested. Especially around weaning, a stable microflora is necessary to prevent the proliferation of pathogens such as E.coli bacteria. Such pathogens can degrade the lysine (the main amino acid for muscle protein production) we have added to our formulations, rendering it useless.

Single molecules (or additives) are able to support the development of gut microflora, boost  its integrity, and therefore help the animals use “traditional nutrients” in a more effective way.

The impact of immune system activation on the performance of pigs

Animal performance is influenced by complex processes, from metabolism to farm biosecurity. Environmental conditions, diet formulation and feed management, and health status, among others, directly affect the amount of the genetic potential that animals can effectively express.

Among these so-called non-genetic variables, health status is one of the most decisive factors for the optimal performance from a given genotype. Due to the occurrence of (sub-) clinical diseases, the inflammatory process can be triggered and may result in a decrease in weight gain and feed efficiency.

Not so long ago, pig producers believed that a maximized immune response would always be ideal for achieving the best production levels. However, after decades spent researching what this “maximized immune response” could mean to our pigs, studies from different parts of the globe proved that an activated immune system could negatively affect animal performance. The perception is nowadays common sense within the global pig production industry.

That understanding led us to increasingly search for production systems that will yield the best conditions for the pigs. This means minimum contact with pathogens, reduced stress factors, and therefore a lower need for an activated immune system.

How immune system stimulation works

The immune system has as main objective to identify the presence of antigens – substances that are not known to the body – and protect the body from these “intruders”. The main players among these substances are bacteria and viruses. However, some proteins can also trigger an immunological reaction. Specific immune cells are responsible for the transfer of information to the other systems of the body so that it can respond adequately. This response from the immune system includes metabolic changes that can affect the demand for nutrients and, therefore, the animals’ growth.

The stimulation of the immune system has three main metabolic consequences:

• behavioral responses
• direct connection with the endocrine system and regulation of the secretions
• release of leukocytes, cytokines, and macrophages

In general, the immune system responds to antigens, releasing cytokines that activate the cellular (phagocytes) and humoral components (antibody), resulting in a decreased feed intake and an increased body temperature/heat production.

When feed formulation is concerned, possibly even more important is to understand that the activation of the immune system leads to a change in the distribution of nutrients. The basal metabolic rate and the use of carbohydrates will have completely different patterns in such an event. For instance, some glucose supplied through the feed follows its course to peripheral tissues; however, part of the glucose is used to support the activated immune system. As a consequence, the energy requirement of the animal increases.

Protein synthesis and amino acid utilization also change during this process. There is a reduction of body protein synthesis and an increased rate of degradation. The nitrogen requirement increases because of the higher synthesis of acute-phase proteins and other immunological cells.

However, increased lysine levels in the diets will not always help the piglets compensate for this shift in the protein metabolism. According to Shurson & Johnston (1998), when the immune system is activated, there is further deamination of amino acids and increased urinary excretion of nitrogen. Therefore we need to understand better which amino acids must be supplied in a challenging situation.

In pigs, the gastrointestinal tract is, to a large extent, responsible for performance. This happens because the gut is the route for absorption of nutrients, but also a reservoir of hundreds of thousands of different microorganisms – including the pathogenic ones.

Understanding  Gut Health

Gut health and its meaning have been the topic of several peer-reviewed articles in the last few decades (Adewole et al., 2016, Bischoff, 2011, Celi et al., 2017, Jayaraman and Nyachoti, 2017, Kogut and Arsenault, 2016, Moeser et al., 2017, Pluske, 2013). Despite the valuable body of knowledge accumulated on the topic, a clear and widely-accepted definition is still lacking.  Kogut and Arsenault (2016) define it in the title of their paper as “the new paradigm in food animal production”. The authors explain it as the “absence / prevention / avoidance of disease so that the animal is able to perform its physiological functions in order to withstand exogenous and endogenous stressors”.

In a recently published paper, Pluske et al. (2018) add to the above definition that gut health should be considered in a more general context. They describe it “a generalized condition of homeostasis in the GIT, with respect to its overall structure and function”. The authors add to this definition that gut health in pigs can be compromised even when no clinical symptoms of disease can be observed. Every stressful factor can undermine the immune response of pigs and, therefore, the animals’ performance.

All good information on this topic leads us to the conclusion that, without gut balance, livestock cannot perform as expected. Therefore, balance is the objective for which we formulate our pigs’ feed.

Current nutritional strategies for a stable gut microbiota

Feeding: quality of raw materials

The photos included here were taken in the field and show that taking action against this reality is a must for keeping animals healthy.

Much of this action is related to farm management. The most effective way to minimize such situations is to implement a strict control system in the feed production sites, including controlling raw material quality.

Additives can be used to improve the safety of raw materials. As already extensively discussed, everything that goes into the intestine of the animals will affect gut health and performance. Therefore,  the potential harmful load of mycotoxins should be taken into account. Besides careful handling at harvest and the proper storage of grains, mycotoxin binders can be applied to further decrease the risk of mycotoxin contamination.

The effect of nutrition on microflora: commercial weaning diet after focusing on gut health

The gut-health-focused formulation of diets must take into account the following essentials:

• decrease of gut pH
• gut wall integrity
• minimization of (pathogenic) microbial growth
• microflora modulation with consequently improved colonization resistance

Gut pH

A lower pH in the stomach slows the passage rate of the feed from the stomach to the small intestine. A longer stay of the feed in the stomach potentially increases the digestion of starch and protein. The secretion of pancreatic juices stimulated by the acidic stomach content will also improve the digestion of feed in the small intestine.

For weaned pigs, it is essential that as little as possible of the substrate will reach the large intestine and be fermented. Pathogens take advantage of undigested feed to proliferate. Lowering these “nutrients” will decrease the risk of bacterial overgrowth.

The same is true where protein sources and their levels are concerned. It is essential to reduce protein content as much as possible and preferably use synthetic (essential) amino acids. The application of such sources of amino acids has been proven long ago, and yet in some cases, it is still not fully utilized. Finally, using highly digestible protein sources should, at this point, be a matter of mere routine.

All these strategies have the same goal: the reduction of undigested substances in the gut. Additionally, the reduction of the protein levels can also decrease the costs of the diets.

Further diet adjustments

Further diet adjustments, such as increasing the sulfur amino acids (SAA) tryptophan and threonine to lysine ratio, must also be considered (Goodband et al., 2014; Sterndale et al., 2017). Although the concept of better balancing tryptophan and threonine are quite clear among nutritionists, SAA are sometimes overestimated. Sulfur amino acids are the major amino acids in proteins related to body maintenance, but not so high in muscle proteins. Therefore, the requirement of SAA must also be approached differently. Unlike lysine, the requirements of SAA tend to be higher in immunologically stimulated animals (Table 1).

Table 1. Effect of the immune system activation on the demand for lysine and sulfur amino acids in pigs (Stahly et al., 1998) 

*ISA – immune system activation

Vitamins and minerals are classic nutrients to be considered when formulating gut health-related diets. Maybe not so extensive as the amino acids and protein levels, these nutrients have, however, been found to carry benefits in challenging situations. In the past several years, a lot was published on the requirements of pigs facing an activation of the immune system. Stahly et al. (1996) concluded that when the immune system is activated, the phosphorous requirements change.

Table 2. Effect of the immune system activation on the performance and phosphorous requirements of pigs (Stahly et al., 1998)

*ISA – immune system activation

Another example is vitamin A. It is involved in the function of macrophages and neutrophils. Vitamin A deficiency decreases the migratory and phagocytic abilities of the immune cells. A lower antibody production is observed in vitamin A deficiency as well. Furthermore, vitamin A is an important factor in mucosal immunity, because this vitamin plays a role in lymphocyte homing in the mucosa (Duriancik et al., 2010).

Phytomolecules: key additives to support gut health

Phytomolecules are currently considered one of the top alternatives to in-feed antibiotics for pigs worldwide. Programs sponsored by the European Union are once more evaluating the effectiveness of these compounds as part of a strategy to produce sustainable pigs with low or no antibiotic use. The EIP-Agri (European Innovation Partnership “Agricultural Productivity and Sustainability”) released a document with suggestions to lower the use of antibiotics in feed by acting in three areas:

• improving pig health and welfare
• changing attitudes and human habits
• finding specific alternatives to antibiotics

Under the last topic, the commission recommends plant-based feed additives to be further examined.

Antibiotics have been used for many years for supporting performance in animal production, especially in critical moments. The mode of action consists of the reduction of pathogen proliferation and inflammation processes in the digestive tract. These (soon-to-be-) banned compounds therefore reduce the activation of the immune system, helping keep pigs healthy through a healthy gastrointestinal tract. As potential alternatives to antibiotic usage, phytomolecules should be able to do the same.

The mode of action of phytomolecules

Antimicrobial

Most phytomolecules used nowadays aim to control the number and type of bacteria in the gut of animals.  According to Burt (2004), the antimicrobial activity of phytomolecules is not the result of one specific mode of action, but a combination of effects on different targets of the cell. This includes disruption of the membrane by terpenoids and phenolics, metal chelation by phenols and flavonoids, and protective effects against viral infections for certain alkaloids and coumarins (Cowan, 1999).

Digestion support

The antimicrobial efficacy is one of the most important activities of secondary plant compounds, but it also impacts digestion. Windisch et al. (2008) states that growth-promoting agents decrease immune defense stress during critical situations. They increase the intestinal availability of essential nutrients for absorption, thus promoting the growth of the animal.

Indeed, phytomolecules are a good tool for stabilizing the gut microbiota. But more can be expected when adding this class of additives into your formulation and/or farm operations. Mavromichalis, in his book “Piglet Nutrition Notes – Volume 2”, brings attention to the advantages of using phytomolecules such as capsaicin, which is often related to increased feed intake. Recent research has demonstrated that capsaicin increases the secretion of digestive enzymes that may result in enhanced nutrient digestibility. According to Mavromichalis, this can lead to a better feed conversion rate as more nutrients are available to the animal. Indirectly, this also helps control the general bacterial load in the gut.

Antioxidant support

This results from the polyphenols’ capacity to act as metal-chelators, free radical scavengers, hydrogen donators, and inhibitors of the enzymatic systems responsible for initiating oxidation reaction. Furthermore, they can act as a substrate for free radicals such as superoxide or hydroxyl, or intervene in propagation reactions.

This variety of benefits explains at least partially the high level of interest in this group of additives for pigs under challenging conditions. For the production of effective blends, it is crucial to understand the different modes of action of the phytomolecules and the probable existing synergies. Furthermore, the production technology  must be considered. For instance, microencapsulation techniques that prevent losses during feed processing are an important consideration.

Not to be discarded: Biosecurity

The recent outbreak of African Swine Fever focused our attention on something that is sometimes neglected on the farm: biosecurity rules. According to the report “Good Practices For Biosecurity In The Pig Sector” (2010), the three main elements of biosecurity are:

• segregation
• cleaning
• disinfection

In general terms, the following steps must be adopted with the clear goal of reducing the challenges that the pigs are facing.

• Farms must be located far from other farms (regardless of the species) and ideally must be protected with natural (forest/woods) or physical barriers.
• Only one entrance must be used to go into the farm (for both vehicles and people) and a disinfection procedure must be in place, either by an automatized system or by manual application of disinfectants. Equipment disinfection systems must also be in place.
• Workers and any other person that enters the facility should adhere to strict biosecurity measures 24/7. The farms must have a visitors’ book including relevant data on previous visits to farms (regardless of the species).
• Trucks and visitors should not have been in contact with other pigs recently (at least 48 hours previous to the visit).
• Only farm workers are allowed to go into the barns unless special approval is given (followed by strict biosecurity measurements prior to the visit).
• The use of clothing and footwear that are worn only in the pig unit (and certainly not during visits to other pig farms) is recommended.
• No materials (e.g. tools) can be moved from one barn to another barn. People that enter a barn should change footwear and wash their hands with soap for at least 10 seconds.

These simple actions can make a big difference to the performance of the pigs, and as a consequence to the profitability of a swine farm.

Take-home messages

Different formulations and reassessed nutritional level recommendations have been on the radar for a couple of years. It is high time to consider using efficient additives to support the pigs’ gut health. Phytomolecules appear as one of the most prominent tools to reduce pathogenic stress in pig production. Either via feed or water, phytomolecules are proven to reduce bacterial contamination and therefore reduce the need for antibiotic interventions. Furthermore, a more careful look at our daily activities in the farm is crucial. Paying attention to biosecurity and to feed safety should be standard tools to improve performance and the success of pig production operations.

References are available upon request.

*The article was initially published in the PROCEEDINGS OF THE PFQC 2019

By Technical Team, EW Nutrition

In modern swine production, one of the key aspects for success is a balanced diet. This essentially means ensuring that the animal meets its daily nutritional requirements for maintenance, growth, and reproduction. In order to provide an appropriate diet and safe feed for the animals, the sensory and nutritional characteristics of the feed must be preserved and issues like the oxidation of the feed must be avoided.

This article aims to highlight why oxidation in  feed can become a big concern for swine producers, what the problems resulting from oxidation in pig feed are, and present practical solutions to improve feed quality and pig performance by controlling the oxidation.

Feed oxidation: What are the dangers?

In pig diets, various sources of lipids are added to increase caloric density, provide essential fatty acids, improve feed palatability, improve pellet quality, and reduce dust (Keer et al., 2015). Some of the feed ingredients are more susceptible to oxidation because of their physical and chemical characteristics, such as milled grains and ingredients of animal origin and vegetable oils with a high content of polyunsaturated fatty acids.

Oxidative rancidity is a type of lipid deterioration. In the oxidation process, the free radicals react with lipids and proteins and induce cellular and tissue damage.

Some consequences of oxidative deterioration are the destruction of fat-soluble vitamins, supplemental fats, and oils. Preserving these ingredients is crucial because fats and oils provide a high quantity of energy and essential fatty acids. At the same time, vitamins, such as those present in vitamin premixes, are indispensable for optimal animal growth and performance.

The oxidation process also results in by-products with strong unpleasant taste and odor, and even toxic metabolites. In addition, oxidized feed has less protein, amino acids, and energy content. All these factors are relevant when resources, in the current scenario of high prices of feed ingredients and inputs, might be wasted due to poor feed management.

Performance losses caused by oxidation

Lipid oxidation can incur several losses regarding the pigs’ performance. Feeding oxidized lipids significantly decreases growth rate, feed intake and efficiency, immune function, and weight gain efficiency in pigs, especially in breeding animals, since the exposure occurs over long periods.

The ingestion of products resulting from the oxidative deterioration of fatty acids leads to irritability of the intestinal mucosa, diarrhea, and, in extreme cases, can result in liver degeneration and cell death. DeRouchey et al. (2004) observed reduced growth rates in pigs that are fed rancid white grease. Ringseis et al. (2007) reported that feeding oxidized sunflower oil increased oxidative stress markers in the small intestine of pigs, while Boler et al. (2012) reported that feeding pigs oxidized corn oil reduced growth performance (Table 1). Lu et al. (2014a) reported signs of liver damage in pigs subjected to dietary oxidative stress, increasing plasma bilirubin content, and enlarged liver size.

Table 1. Effects of dietary corn oil quality and antioxidant inclusion on barrow performance (Source: Boler et al., 2012)

There are some theories as to why oxidized feed causes such effects. According to Dibner et al. (1996), vitamins and polyunsaturated fatty acids deteriorate in the absence of antioxidants, and oxidized fats and their byproducts can negatively affect cells, resulting in changes in membrane permeability, viscosity, secretory activity, and membrane-bound enzyme activity. These primary effects lead to observable systemic effects. In order to prevent these damaging consequences, antioxidants have become a widely used alternative.

The power of antioxidants

Chemical antioxidants (Table 2) are added to animal feeds to delay fat and vitamin oxidation, which keeps the diet palatable and helps prolong the feed’s shelf life, ultimately maintaining the quality of the ingredients (Jacela et al., 2010). They prevent the binding of oxygen to free radicals. Dietary antioxidants have also been used in several species of animals to replace vitamin E, which is known for its antioxidant powers. Antioxidants are highly applicable in warm climates, when high levels of fat are added to the diet, and in areas where byproducts high in unsaturated fats are commonly used.

Table 2. Commonly used chemical antioxidants

Lu et al. (2014b) studied the effects of dietary supplementation with a blend of antioxidants (ethoxyquin and propyl gallate) on carcass characteristics, meat quality, and fatty acid profile in finishing pigs fed a diet high in oxidants. They reported that the inclusion of antioxidants minimized the effects of the high oxidant diet. The treatments including antioxidants, whether combined with vitamin E or not, had positive results in carcass weight, back fat, loin characteristics, and extractable lipid percentage.

Fernandez-Duenas (2009) studied the use of antioxidants in feed containing fresh or oxidized corn oil and its effects on animal performance, the oxidative status of tissues, meat quality, shelf life, and the antioxidant activity of skeletal muscle of finishing pigs. They reported that barrows fed with diets with the antioxidant blend showed increased feed efficiency. Orengo et al. (2021) showed that feeds protected with antioxidants could compensate for low vitamin E supply with regard to growth performance in the starter phase. Hung et al., 2017 theorized that the impacts on growth performance are likely related to the lack of adequate antioxidant capacity of the diet and oxidative stress status.

As literature and application results show, the use of antioxidants in pig feed is crucial to minimize adverse effects from oxidized feed and allow the animals to express their full performance potential.

SANTOQUIN: preserving feed quality

From a practical standpoint, swine producers must consider some criteria for selecting a good antioxidant, which must preserve feed components, be nontoxic for humans and pigs, show effectiveness at very low concentrations, and be economically sustainable.

Considering those major characteristics, EW Nutrition offers a range of antioxidant solutions for the preservation of feed ingredients and feeds for poultry and swine through their SANTOQUIN product line. Santoquin is a feed preservative that protects supplemental fats, oils, meals, and vitamin premixes and protect feed from oxidation. Santoquin provides unsurpassed protection from oxidative rancidity, and it has proven effects against oxidation in feeds (Figure 1) ensuring the prolonged shelf life of feeds, especially during suboptimal storage conditions, such as those with high environmental temperature and elevated levels of moisture.

Figure 1. Antioxidant efficacy and competitiveness. SANTOQUIN MAX feed preservative is a proprietary antioxidant blend that effectively prolongs the shelf life of feed and feed ingredients by reducing oxidation rate.

Studies have been conducted to show the beneficial effects of Santoquin. Ethoxyquin, contained in Santoquin, has been used in the swine industry for over five decades and has been shown to improve growth performance and markers of oxidative status in pigs (Dibner et al., 1996). Ethoxyquin is also known for being the most efficacious and cost-effective antioxidant. Lu et al. (2014b) showed that the addition of an antioxidant blend (ethoxyquin and propyl gallate) protected pigs fed with a high-oxidant diet from oxidative stress more efficiently than vitamin E supplementation (Figure 2).

Figure 2. Concentrations of vitamins A and E across treatments in the plasma (A) and muscle (B). HO: high oxidant diet containing 5% oxidized soybean oil (peroxide value at approximately 180 mEq/kg of oil, 9 mEq/kg in the diet) and 10% of a PUFA source (providing approximately 55.57% of crude fat that contains docosahexaenoic acid [ DHA] at 36.75%, and 2.05% DHA in the diet); VE: the HO diet with 11 IU/kg of added vitamin E; AOX: the HO diet with an antioxidant blend (ethoxyquin and propyl gallate, 135 mg/kg); VE+AOX: the HO diet with both vitamin E and antioxidant blend; SC: a standard corn–soy control diet with nonoxidized oil and no PUFA source. The HO pigs were switched to the SC diet after day 82 as an intervention for poor health and performance. The samples came from two pigs from each pen. The VE treatment lost 1 replicate during the feeding phase and transportation period (n = 4), while in other treatments, n =5. (Source: Lu et al., 2014b)

Conclusion

The negative effects of oxidation in pig feed can result in diets with lower biological energy value. To avoid that, antioxidants help maintain intestinal health, ensure a safe food intake, preserve the ingredients and resources used in pig production. Overall, antioxidants help swine producers improve feed conversion and achieve more productive animals and lower mortality caused by toxicity. At the end of the day, the use of antioxidants is associated with better profitability.

References

Boler, D. D., Fernández-Dueñas, D. M., Kutzler, L. W., Zhao, J., Harrell, R. J., Campion, D. R., Mckeith, F. K., Killefer, J., & Dilger, A. C. (2012). Effects of oxidized corn oil and a synthetic antioxidant blend on performance, oxidative status of tissues, and fresh meat quality in finishing barrows. Journal of Animal Science, 90(13), 5159–5169. https://doi.org/10.2527/jas.2012-5266

DeRouchey, J. M., Hancock, J. D., Hines, R. H., Maloney, C. A., Lee, D. J., Cao, H., Dean, D. W., & Park, J. S. (2004). Effects of rancidity and free fatty acids in choice white grease on growth performance and nutrient digestibility in weanling pigs. Journal of Animal Science, 82(10), 2937–2944. https://doi.org/10.2527/2004.82102937x

Dibner, J. J., Atwell, C. A., Kitchell, M. L., Shermer, W. D., & Ivey, F. J. (1996). Feeding of oxidized fats to broilers and swine: Effects on enterocyte turnover, hepatocyte proliferation and the gut associated lymphoid tissue. Animal Feed Science and Technology, 62(1 SPEC. ISS.), 1–13. https://doi.org/10.1016/S0377-8401(96)01000-0

Fernández-dueñas, D. M. (2009). Impact of oxidized corn oil and synthetic antioxidant on swine performance, antioxidant status of tissues, pork quality, and shelf life evaluation.

Hung, Y. T., Hanson, A. R., Shurson, G. C., & Urriola, P. E. (2017). Peroxidized lipids reduce growth performance of poultry and swine: A meta-analysis. Animal Feed Science and Technology, 231, 47–58. https://doi.org/10.1016/j.anifeedsci.2017.06.013

Jacela, J. Y., DeRouchey, J. M., Tokach, M. D., Goodband, R. D., Nelssen, J. L., Renter, D. G., & Dritz, S. S. (2010). Feed additives for swine: Fact sheets–flavors and mold inhibitors, mycotoxin binders, and antioxidants. Journal of Swine Health and Production, 18(1), 27-32.

Kerr, B. J., Kellner, T. A., & Shurson, G. C. (2015). Characteristics of lipids and their feeding value in swine diets. Journal of Animal Science and Biotechnology, 6(1), 1-23. https://doi.org/10.1186/s40104-015-0028-x

Lu, T., Harper, A. F., Zhao, J., Estienne, M. J., & Dalloul, R. A. (2014). Supplementing antioxidants to pigs fed diets high in oxidants: I. Effects on growth performance, liver function, and oxidative status. Journal of animal science, 92(12), 5455-5463. https://doi.org/10.2527/jas.2013-7109

Lu, T., Harper, A. F., Dibner, J. J., Scheffler, J. M., Corl, B. A., Estienne, M. J., Zhao, J., & Dalloul, R. A. (2014b). Supplementing antioxidants to pigs fed diets high in oxidants: II. Effects on carcass characteristics, meat quality, and fatty acid profile. Journal of Animal Science, 92(12), 5464–5475. https://doi.org/10.2527/jas.2013-7112

Orengo, J., Hernández, F., Martínez-Miró, S., Sánchez, C. J., Peres Rubio, C., & Madrid, J. (2021). Effects of commercial antioxidants in feed on growth performance and oxidative stress status of weaned piglets. Animals, 11(2), 1–13. https://doi.org/10.3390/ani11020266

Ringseis, R., Piwek, N., & Eder, K. (2007). Oxidized fat induces oxidative stress but has no effect on NF-κB-mediated proinflammatory gene transcription in porcine intestinal epithelial cells. Inflammation Research, 56(3), 118–125. https://doi.org/10.1007/s00011-006-6122-y

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

Freitas Barbosa, Fellipe, Silvano Bünzen. Produção de suínos em épocas de restrição aos antimicrobianos–uma visão global. In: Suinocultura e Avicultura: do básico a zootecnia de precisão (2021): 14-33. https://dx.doi.org/10.37885/210203382

Correa-Fiz, Florencia, José Maurício Gonçalves dos Santos, Francesc Illas and Virginia Aragon, “Antimicrobial removal on piglets promotes health and higher bacterial diversity in the nasal microbiota,” Scientific reports 9, no. 1 (2019): 1-9. https://doi.org/10.1038/s41598-019-43022-y

Food and Drug Administration [FDA]. 2019. Animal drugs and animal food additives. Avaliable at: https://www.fda.gov/animalveterinary/development-approval-process/veterinary-feeddirective-vfd

Stein, Hans H , “Experience of feeding pigs without antibiotics: a European perspective,” Animal Biotechnology 13 no. 1(2002): 85-95. https://doi.org/10.1081/abio-120005772

Helm, Emma T, Shelby Curry, Julian M Trachsel, Martine Schroyen, Nicholas K Gabler, “Evaluating nursery pig responses to in-feed sub-therapeutic antibiotics”, PLoS One 14 no. 4 (2019). https://doi.org/10.1371/journal.pone.0216070.

Hengxiao Zhai, Hong Liu, Shikui Wang, Jinlong Wu and Anna-Maria Kluenter, “Potential of essential oils for poultry and pigs,” Animal Nutrition 4, no. 2 (2018): 179-186. https://doi.org/10.1016/j.aninu.2018.01.005

Pluske, J. R., Kim, J. C., Black, J. L. “Manipulating the immune system for pigs to optimise performance,” Animal Production Science 58, no 4, (2018): 666-680. https://doi.org/10.1071/an17598

Zimmerman, Jeffrey, Locke Karriker, Alejandro Ramirez, Kent Schwartz, Gregory Stevenson, Jianqiang Zhang (Eds.), “Diseases of Swine,” 11 (2019), Wiley Blackwell.

Campbell, Joy M, Joe D Crenshaw & Javier Polo, “The biological stress of early weaned piglets”, Journal of animal science and biotechnology 4, no. 1 (2013):1-4. https://doi.org/10.1186/2049-1891-4-19

Jung M. Heo, Opapeju, F. O., Pluske, J. R., Kim, J. C., Hampson, D. J., & Charles M. Nyachoti, “Gastrointestinal health and function in weaned pigs: a review of feeding strategies to control post‐weaning diarrhoea without using in‐feed antimicrobial compounds,” Journal of animal physiology and animal nutrition 97, no. 2 (2013): 207-237. https://doi.org/10.1111/j.1439-0396.2012.01284.x

Junjie Jiang, Daiwen Chen, Bing Yu, Jun He, Jie Yu, Xiangbing Mao, Zhiqing Huang, Yuheng Luo, Junqiu Luo, Ping Zheng, “Improvement of growth performance and parameters of intestinal function in liquid fed early weanling pigs,” Journal of animal science 97, no. 7 (2019): 2725-2738. https://doi.org/10.1093/jas/skz134

Cardinal, Kátia Maria, Ines Andretta, Marcos Kipper da Silva, Thais Bastos Stefanello, Bruna Schroeder and Andréa Machado Leal Ribeiro, “Estimation of productive losses caused by withdrawal of antibiotic growth promoter from pig diets – Meta-analysis,” Scientia Agricola 78, no.1 (2021): e20200266. http://doi.org/10.1590/1678-992X-2020-0266

Cardinal, Katia Maria, Marcos Kipper, Ines Andretta and Andréa Machado Leal Ribeiro, “Withdrawal of antibiotic growth promoters from broiler diets: Performance indexes and economic impact,” Poultry science 98, no. 12 (2019): 6659-6667. https://doi.org/10.3382/ps/pez536

Mazutti, Kelly, Leandro Batista Costa, Lígia Valéria Nascimento, Tobias Fernandes Filho, Breno Castello Branco Beirão, Pedro Celso Machado Júnior, Alex Maiorka, “Effect of colistin and tylosin used as feed additives on the performance, diarrhea incidence, and immune response of nursery pigs”, Semina: Ciências Agrárias 37, no. 4 (2016): 1947. https://doi.org/10.5433/1679-0359.2016v37n4p1947

Lee, Kwang-Geun and Takayuki Shibamoto, “Antioxidant activities of volatile components isolated from Eucalyptus species,” Journal of the Science of Food and Agriculture 81, no. 15 (2001): 1573-1579. https://doi.org/10.1002/jsfa.980

Long, S. F., Xu, Y. T., Pan, L., Wang, Q. Q., Wang, C. L., Wu, J. Y., … and Piao, X. S. Mixed organic acids as antibiotic substitutes improve performance, serum immunity, intestinal morphology and microbiota for weaned piglets,” Animal Feed Science and Technology 235, (2018): 23-32.

Davies, Madlen and Timothy R. Walsh, “A colistin crisis in India,” The Lancet. Infectious diseases 18, no. 3 (2018): 256-257. https://doi.org/10.1016/s1473-3099(18)30072-0

Castillo, Marisol, Susana M Martín-Orúe, Miquel Nofrarías, Edgar G Manzanilla and Josep Gasa, “Changes in caecal microbiota and mucosal morphology of weaned pigs”, Veterinary microbiology 124, no. 3-4 (2007): 239-247. https://doi.org/10.1016/j.vetmic.2007.04.026

Dyar, Oliver J, Jia Yin, Lilu Ding, Karin Wikander, Tianyang Zhang, Chengtao Sun, Yang Wang, Christina Greko, Qiang Sun and Cecilia Stålsby Lundborg, “Antibiotic use in people and pigs: a One Health survey of rural residents’ knowledge, attitudes and practices in Shandong province, China”, Journal of Antimicrobial Chemotherapy 73, no. 10 (2018): 2893-2899. https://doi.org/10.1093/jac/dky240

Prudius, T. Y., Gutsol, A. V., Gutsol, N. V., & Mysenko, O. O “Globigen Jump Start usage as a replacer for blood plasma in prestarter feed for piglets,” Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies, Series: Agricultural sciences 23, no. 94 (2021): 111-116. https://doi.org/10.32718/nvlvet-a9420

Guevarra, Robin B., Jun Hyung Lee, Sun Hee Lee, Min-Jae Seok, Doo Wan Kim, Bit Na Kang, Timothy J. Johnson, Richard E. Isaacson and Hyeun Bum, “Piglet gut microbial shifts early in life: causes and effects,” Journal of animal science and biotechnology 10, no. 1 (2019): 1-10. https://dx.doi.org/10.1186%2Fs40104-018-0308-3

Waititu, Samuel M., Jung M. Heo, Rob Patterson and Charles M. Nyachoti, “Dose-response effects of in-feed antibiotics on growth performance and nutrient utilization in weaned pigs fed diets supplemented with yeast-based nucleotides,” Animal Nutrition 1, no. 3 (2015): 166-169. https://doi.org/10.1016/j.aninu.2015.08.007

Xiaoyu Li, Ying Yao, Xitao Wang, Yuhong Zhen, Philip A Thacker, Lili Wang, Ming Shi, Junjun Zhao, Ying Zong, Ni Wang, Yongping Xu. “Chicken egg yolk antibodies (IgY) modulate the intestinal mucosal immune response in a mouse model of Salmonella typhimurium infection,” International immunopharmacology 36, (2016) 305-314. https://doi.org/10.1016/j.intimp.2016.04.036

Yunsheng Han, Tengfei Zhan, Chaohua Tang, Qingyu Zhao, Dieudonné M Dansou, Yanan Yu, Fellipe F Barbosa, Junmin Zhang. Effect of Replacing in-Feed Antibiotic Growth Promoters with a Combination of Egg Immunoglobulins and Phytomolecules on the Performance, Serum Immunity, and Intestinal Health of Weaned Pigs Challenged with Escherichia coli K88. Animals 11, no. 5 (2021): 1292. https://doi.o

by Inge Heinzl, Editor, and Marisabel Caballero, Global Technical Manager Poultry, EW Nutrition

What is your most crucial key feed performance indicator? We posted this question on an online professional platform and got more than 330 answers from professionals in the industry:

• 55 % of the respondents considered feed efficiency or feed conversion rate (FCR) the key indicator, and
• 35 % listed feed cost / kg produced as their most important indicator.

As feed represents 60-70 % of the total production costs, feed efficiency has a high impact on farm profitability – especially in times of high feed prices. Furthermore, for the meat industry, an optimal FCR is essential for competitiveness against other protein sources. Finally, for food economists, feed efficiency is connected to the optimal use of natural resources (Patience et al., 2015).

In this article, we explain the factors that influence feed efficiency and show options to support animals in optimally utilizing the feed – directly improving the profitability of your operation.

How to measure the feed conversion rate

The FCR shows how efficiently animals utilize their diet for maintenance and net production. In the case of fattening animals, it is meat production; for dairy cows, it is milk, and for layers, it is egg mass (kg) or a specific egg quantity.

The feed conversion rate is the mathematical relation obtained by dividing the amount of feed the animal consumed by the production it provided. The FCR is an index for the degree of feed utilization and shows the amount of feed needed by the animal to produce one kg of meat or egg mass, or, e.g., 10 eggs.

When comparing the FCRs of different groups of animals (e.g., from different houses or farms), some considerations are important:

• Feed consumed is not feed disappeared: Due to differences in feeder design and feeder adjustment, these two values can differ by 10-30 %. If FCR is calculated for economic purposes, the wasted feed must be included, as it causes costs and must be paid by the farmer. However, if FCR is calculated for scientific purposes (e.g., a performance trial), only the feed consumed should be included.
• Even if they are same-aged animals, individuals or groups differ in weight. Hence, they have different requirements for maintenance and also diverging quantity left for production. To avoid mistakes, weight-corrected FCR can be used.
• Nutrient utilization also depends on genotype and sex; thus, comparisons should consider these factors as they also influence weight gain and body composition (Patience et al., 2015).

Many factors influence the FCR

There are internal and external factors that influence feed efficiency. Internal factors originate in the animal and include genetics, age, body composition, and health status. In contrast, external factors include feed composition, processing, and quality, as well as the environment, welfare enrichment, and social aspects.

1. Species

Different species have different body sizes and physiology and, therefore, vary in their growth and maintenance requirements, impacting their efficiency in converting the feed.

Table 1: FCRs of different species

Compared to terrestrial animals, for example, fish and other aquatic animals have a low FCR. Being poikilothermic (animals whose body temperature ranges widely), they don’t spend energy on maintaining their body temperature if the surrounding water is within their optimal range. As they are physically supported by water, they also need less energy to work against gravity. Furthermore, carnivorous fish are offered highly digestible, nutrient-dense feed, which lowers their requirements in quantity. Omnivorous fish, on the other hand, also consume feedstuffs not provided by the producer (e.g., algae and krill), which is not considered in the calculation. Broilers are the only farm animals achieving a similar FCR.

2. Sex, age, and growth phase

Sex determines gene expression related to the regulation of feed intake and nutrient utilization. Males have a better feed conversion and put on more lean meat than females and castrates, which grow slower and easier run to fat.

Young animals have a fast growth rate and are offered nutritionally dense feed; hence, their FCR is lower. When the animal grows and gains weight, its energy requirement for maintenance increases and its growth rate and the feed nutrient density diminish.

Table 2: FCR during different life phases of pigs (based on Adam and Bütfering, 2009)

3. Health and gut health

Health decisively impacts feed conversion. An animal that is challenged by pathogens reduces its feed intake and, thus, decreases growth. Additionally, the body needs energy for the immune defense, the replacement of damaged or lost tissue, and heat production, in case of fever. As many immune components are rich in protein, this is the first nutrient to become limited.

An imbalance in the gut microbiome also impacts feed conversion: pathogenic microorganisms damage tissues, impair nutrient digestion and absorption, and their metabolic products are harmful. Furthermore, pathogens consume nutrients intended for the host and continue to proliferate at its expense.

4. Environment

The environment influences the way the animals spend their maintenance energy. According to Patience (2012), when a 70 kg pig is offered feed ad libitum, 34 % of the daily energy is used for maintenance. For each °C below the thermoneutral zone, an additional 1.5% of feed is needed for maintenance. In heat stress, each °C above the optimum range decreases feed intake by 2%. Therefore, the feed needs to be denser to fulfill the requirement, or the animal will lose weight. Social stress also influences animal performance, especially chronic stress situations. Keeping the animals in their thermoneutral zone and mitigating the impact of stressors means more energy can go towards performance.

5. Feed quantity, composition, and quality

The feed is the source of nutrients animals convert into production. So, it’s natural that its quality and composition, and the availability of nutrients affect feed efficiency.

Better FCR by increasing nutrient density and digestibility

Higher energy content in the diet and better protein digestibility improve FCR. Saldaña et al. (2015) assert that increasing the energy content of a diet led to a linear decrease of the average daily feed intake but improved FCR quadratically. The energy intake by itself remained equal. However, these diet improvements also increase costs, and a cost-benefit analysis should be conducted.

Feed form and particle size play an important role

Feed processing can improve nutrient utilization. Particle size, moisture content, and whether the feed is offered as pellets or mash influence feed efficiency. Reducing the particle size leads to a higher contact surface for digestive enzymes and higher digestibility. Chewning et al. (2012) tested the effect of particle size and feed form on FCR in broilers. They found that pellet diets enable better FCRs than mash diets – one reason is the lower feed waste, another one the smaller feed particle size in the pelleted feed. Comparing the different tested mash diets, the birds receiving feed with a particle size of 300 µm performed better than the birds getting a diet with 600 µm particles.

Richert and DeRouchey (2015) show that pigs’ feed efficiency improved by 1.3 % for every 100 µm when the particle size was reduced from 1000 µm to 400 µm , as the contact surface for the digestible enzymes increased. In weaning piglets of 28-42 days, the increase of particle size from 394 µm to 695 µm worsened FCR from 1.213 to 1.245 (Almeida et al., 2020). There is a flipside to smaller particle size as well, however: high quantities of fines in the diet can lead to stomach ulceration in pigs (Vukmirović et al., 2021).

Non-starch polysaccharide (NSP)-rich cereals worsen FCR

The carbohydrates in feedstuffs such as wheat, rye, and barley are not only energy suppliers, and if not managed well, the inclusion of these raw materials can deteriorate feed conversion. Vegetable structural substances such as cellulose, hemicellulose, or lignin (e.g., in bran), are difficult or even impossible to utilize as they lack the necessary enzymes.

Figure 1: Contents of arabinoxylan and ß-glucan in grain (according to Bach Knudsen, 1997)

Additionally, water-soluble NSPs (e.g., pectins, but also ß-glucans and pentosans) have a high water absorption capacity. These gel-forming properties increase the viscosity of the digesta. High viscosity reduces the passage rate and makes it more difficult for digestive enzymes and bile acids to come into contact with the feed components. Also, nutrients’ contact with the resorptive surface is reduced.

Another disadvantage of NSPs is their “cage effect.” The water-insoluble NSPs cellulose and hemicellulose trap nutrients such as proteins and digestible carbohydrates. Consequently, again, digestive enzymes cannot reach them, and they are not available to the organism.

Molds and mycotoxins impair feed quality, but also animal health

Molds reduce the nutrient and energy content of the feed and negatively impact feed efficiency. They are dependent on active water in the feed and feed ingredients. Compared to bacteria, which need about 0.9-0.97 Aw (active water), most molds require only 0.86 Aw.

Table 3: Comparison of 28-day-old chicks performance fed not-infested and molded corn

Besides spoiling raw materials and feed and reducing their nutritional value, molds also produce mycotoxins which negatively impact animal health, including gut health. They damage the intestinal villi and tight junctions, reducing the surface for nutrient absorption. In a trial with broiler chickens, Kolawole et al. (2020) showed a strong positive correlation between the FCR and the exposure to different mycotoxins. The increase in levels of toxin mixtures resulted in poor FCR. Williams and Blaney (1994) found similar results with growing pigs. The animals received diets containing 50 % and 75 % of corn with 11.5 mg nivalenol and 3 mg zearalenone per kg. The inclusion of contaminated corn led to a deterioration of feed efficiency from 2.45 (control) to 3.49 and 3.23.

Oxidation of fats also affects feed quality

DDGS (distiller’s dried grains with solubles), by-products of corn distillation processes, are often used as animal feed, especially for pigs. The starch content is depleted in the distillation process and thus removed. The fat, however, is concentrated, and DDGS reach a similar energy content as corn.

Pigs also receive fats from different sources (e.g., soybean or corn oil, restaurant grease, animal-vegetable blends), especially in summer. Due to heat, the animals eat less, so increasing energy density in the feed is a possibility to maintain the energy intake.  The high fat content, however, makes these feeds susceptible to oxidation at high temperatures.

The oxidation of feedstuffs manifests in the rancidity of fats, destruction of the fat-soluble vitamins A, D, and E, carotenoids (pigments), and amino acids, leading to a lower nutritional value of the feed.

Use adequate supplements to enhance FCR

The feed industry offers many solutions to improve the FCR for different species. They usually target the animal’s digestive health or maintain/enhance feed quality, including increasing nutrient availability.

1. Boost your animals’ gut health

Producers can improve gut health by preventing the overgrowth of harmful microorganisms and by mitigating the effects of harmful substances. For this purpose, two kinds of feed additives are particularly suitable: phytomolecules and products mitigating the impact of toxins and mycotoxins.

Phytomolecules help stabilize the balance of the microbiome

By preventing the proliferation of pathogens, phytomolecules help the animal in three ways:

1. They prevent pathogens from damaging the gut wall
2. They deter and mitigate inflammation
3. By inhibiting the overgrowth of pathogens, they promote better nutrient utilization by the animal

Only a healthy gut can optimally digest feed and absorb nutrients.

In trials testing the phytogenic Activo product range, supplemented animals showed the following FCR improvements compared to non-supplemented control groups (Figure 2).  Note that phy­tomolecules also have a digestive effect that contributes to the FCR improvements:

Figure 2: FCR improvements for animals receiving Activo

Products mitigating the adverse effects of toxins

Both mycotoxins and bacterial toxins negatively impact gut health. Mycotoxins are ingested with the feed; bacterial toxins appear when certain bacteria proliferate in the gut, e.g., gram-negative bacteria releasing LPS or Clostridium perfringens producing NetB and Alpha-toxin.

Products that mitigate the harmful effects of toxins help to protect gut health and maintain an optimal feed efficiency, as shown with a trial conducted with Mastersorb Gold:

Table 4: Trial design, the impact of Mastersorb Gold on broilers challenged with zearalenone and DON-contaminated feed

Figure 3: Average FCR for broilers, with or without zearalenone and DON challenge, with or without Mastersorb Gold supplementation

2. Improve nutrient utilization

Maximum use of the nutrients contained in the feed can be obtained with the help of feed additives that promote digestion. Targeting the animal, selected phytomolecules are used for their digestive properties. Focusing on the feed, specific enzymes can unlock nutrients and thus improve feed efficiency.

Phytomolecules support the animal’s digestive system

Phytomolecules promote optimal digestion and absorption of nutrients by stimulating the secretion of digestive juices, such as saliva or bile, enhancing enzyme activity, and favoring good GIT motility (Platel and Srinivasan, 2004). FCR improvements thanks to the use of a phy­tomolecules-based product (Activo) are shown in figure 2.

Enzymes release more nutrients from feed

Enzymes can degrade arabinoxylans, for example. Arabinoxylans are the most common NSP fraction in all cereals – and are undigestible for monogastric animals. Enzymes can make these substances available for animals, allowing for complete nutrient utilization.  Additionally, nutrients trapped due to the cage effect are released, altogether increasing the energy content of the diet and improving FCR.

3. Be proactive about preserving feed quality

The quality of feed can deteriorate, for instance, when nutrients oxidize, or mold infestation occurs. Oxidation by-products promote oxidative stress in the intestine and may lead to tissue damage. Molds, in turn, take advantage of the nutrients contained in the feed and produce mycotoxins. Both cases illustrate the importance of preventing feed quality issues. Feed additives such as antioxidants and mold inhibitors mitigate these risks.

Antioxidants prevent feed oxidation

Antioxidants scavenge free radicals and protect the feed from spoilage. In animals, they mitigate the adverse effects of oxidative stress. Antioxidants in pig nutrition can stabilize DDGS and other fatty ingredients in the feed, maintaining nutrient integrity and availability. Figure 4 shows the FCR improvement that a producer in the US obtained when using the antioxidant product Santoquin in pork finisher diets containing 30% DDGS.

Figure 4: FCR improvement in pigs receiving Santoquin (trial with a Midwest pork producer)

In DDGS-free diets, which are more common in poultry production, antioxidants also help optimize FCR, as shown by the results of a comprehensive broiler field study in 2015 (figure 5).

Figure 5: FCR in broilers receiving Santoquin, compared to a non-supplemented control group

Inhibiting molds and keeping feed moisture

To round off the topic of feed quality preservation, one should consider mold inhibitors, which also play an essential role. Used at the feed mill, these products blend two types of ingredients with their different modes of action: surfactants and organic acids. Surfactants bind active water so that the moisture of the feed persists, but fungi cannot survive. Organic acids, on the other hand, have anti-fungal properties, directly acting against molds. Both actions together prevent the reduction of energy in the feed, keeping feed efficiency at optimal levels.

Conclusion

The improvement of feed efficiency ranks as one of the most, if not the most, critical measures to cope with rising feed costs. By achieving optimal nutrient utilization, producers can make the most out of the available raw materials.

The feed industry offers diverse solutions to support animal producers in optimizing feed efficiency. Improving gut health, mitigating the negative impact of harmful substances, and maintaining feed quality are crucial steps to achieving the best possible FCR and, hence, cost-effective animal production.

References

Adam, F., and L. Bütfering. “Wann Müssen Meine Schweine an Den Haken?” top agrar. top agrar online, October 1, 2009. https://www.topagrar.com/schwein/aus-dem-heft/wann-muessen-meineschweine-an-den-haken-9685161.html.

Almeida, Leopoldo Malcorra, Vitor Augusto Zavelinski, Katiucia Cristine Sonálio, Kariny Fonseca da Silva, Keysuke Muramatsu, and Alex Maiorka. “Effect of Feed Particle Size in Pelleted Diets on Growth Performance and Digestibility of Weaning Piglets.” Livestock Science 244 (2021). https://doi.org/10.1016/j.livsci.2020.104364.

Chewning, C.G., C.R. Stark, and J. Brake. “Effects of Particle Size and Feed Form on Broiler Performance.” Journal of Applied Poultry Research 21, no. 4 (2012): 830–37. https://doi.org/10.3382/japr.2012-00553.

Gaines, A. M., B. A. Peerson, and O. F. Mendoza. “Herd Management Factors That Influence Whole Feed Efficiency.” Essay. In Feed Efficiency in Swine, edited by J. Patience, 15–39. Wageningen Academic, 2012.

Kolawole, Oluwatobi, Abigail Graham, Caroline Donaldson, Bronagh Owens, Wilfred A. Abia, Julie Meneely, Michael J. Alcorn, Lisa Connolly, and Christopher T. Elliott. “Low Doses of Mycotoxin Mixtures below EU Regulatory Limits Can Negatively Affect the Performance of Broiler Chickens: A Longitudinal Study.” Toxins 12, no. 7 (2020): 433. https://doi.org/10.3390/toxins12070433.

Patience, J. F. “The Influence of Dietary Energy on Feed Efficiency in Grow-Finish Swine.” Essay. In In Feed Efficiency in Swine, edited by J. Patience, 15–39. Wageningen Academic, 2012.

Patience, John F., Mariana C. Rossoni-Serão, and Néstor A. Gutiérrez. “A Review of Feed Efficiency in Swine: Biology and Application.” Journal of Animal Science and Biotechnology 6, no. 1 (2015). https://doi.org/10.1186/s40104-015-0031-2.

Platel, K., and K. Srinivasan. “Digestive Stimulant Action of Spices: A Myth or Reality?” Indian J Med Res, pp 167-179 119 (May 2004): 167–79. http://www.ncbi.nlm.nih.gov/pubmed/15218978

Richert, B. T., and J. M. DeRouchey. “Swine Feed Processing and Manufacturing.” Pork Information Gateway, September 14, 2015. https://porkgateway.org/resource/swine-feed-processing-and-manufacturing/.

Saldaña, B., P. Guzmán, L. Cámara, J. García, and G.G. Mateos. “Feed Form and Energy Concentration of the Diet Affect Growth Performance and Digestive Tract Traits of Brown-Egg Laying Pullets from Hatching to 17 Weeks of Age.” Poultry Science 94, no. 8 (2015): 1879–93. https://doi.org/10.3382/ps/pev145.

Vukmirović, Đuro, Radmilo Čolović, Slađana Rakita, Tea Brlek, Olivera Đuragić, and David Solà-Oriol. “Importance of Feed Structure (Particle Size) and Feed Form (Mash vs. Pellets) in Pig Nutrition – A Review.” Animal Feed Science and Technology 233 (2017): 133–44. https://doi.org/10.1016/j.anifeedsci.2017.06.016.

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

How lipopolysaccharides cause disease

LPS are rather large and structured chemical molecules with a weight of over 100,000 D. They are highly thermostable; boiling in water at 100°C for 30 minutes does not destabilize their structure. LPS consist of three chemically distinct sections: a) the innermost part, lipid A, consisting mostly of fatty acids; b) the core, which contains an oligosaccharide; and c) the outer section, a chain of polysaccharides called O-antigen (Figure 1).

Figure 1: Structure of an LPS

The toxicity of LPS is mainly caused by lipid A; however, both lipid A and O-antigen stimulate the immune system. This happens when the LPS pass the mucosa and enter the bloodstream or when they attack the leukocytes.

The intestinal mucosa is the physical immune barrier that protects the microvilli from external agents (bacteria, free LPS viruses, etc.). Despite its strength (the thickness, for example, amounts to ≈830 µm in the colon and ≈123 µm in the jejunum), vulnerable points exist (cf. Zachary 2017).

LPS can easily come into contact with the cells of the lamina propria (a layer of connective tissue underneath the epithelium) through the microfold (M) cells of the Peyer’s patches (which consist of gut-associated lymphoid tissue). The M cells are not covered by mucus and thus exposed.

Secondly, LPS can also pass through the mucosa, where they become entangled in this gelatinous structure. There, they come into contact with the lymphocytes or can reach the regional lymph nodes through the afferent lymphatic vessels.

Thirdly, LPS might affect the tight junctions, the multiprotein complexes that keep the enterocytes (cells that form the intestinal villi) cohesive. By destabilizing the protein structures and triggering enzymatic reactions that chemically degrade them, LPS can break the tight junctions, reaching the first capillaries and, consequently, the bloodstream.

The presence of endotoxins in the blood, endotoxemia, can trigger problematic immune responses in animals. An innate immune stimulation leads to an increase in the concentration of pro-inflammatory cytokines in the blood and, consequently, to an induced febrile response in the animal: heat production increases, while the available metabolic energy decreases.  As a result, performance suffers, and in the worst-case scenario, septic shock sets in. Furthermore, when LPS compromise intestinal integrity, the risk of secondary infections increases, and production performance may decline.

LPS’ modes of action

How does all of this happen? The physiological consequences of endotoxemia are quite complex. Simplified, the immune system response to LPS in the blood takes three forms:

• The stimulation of TLR4 (toll-like receptor 4) induces monocytes and macrophages to secrete critical pro-inflammatory cytokines, primarily interleukin (IL) IL-1β, IL-6, IL-8, and tumor necrotic factor (TNF) α and β. TLR4 is a structure on the cell membrane of mainly macrophages and leukocytes, which is activated by the LPS-binding protein (LBP).
• The complement cascade constitutes about 10% of plasma proteins and determines the chemotaxis and activation of leukocytes. It can form a membrane attack complex (MAC), which perforates the membranes of pathogenic cells, enabling lysis.
• The Hagemann factor, also known as coagulation factor XII: once stimulated by LPS, it initiates the formation of fibrin (through the intrinsic coagulation pathway), which might lead to thrombosis. The Hagemann factor directly stimulates the transformation of prekallikrein to kallikrein (enzymes involved in regulating blood pressure).

Figure 2: How LPS leads to endotoxemia – 3 modes of action

These three modes of action of inflammatory stimulation lead to important physiological reactions:

• Pro-inflammatory cytokines (see above) modulate the functional expression of other immune cell types during the inflammatory response;
• Metabolites of arachidonic acid (prostaglandins, leukotrienes, and lipoxins), intra- and extracellular messengers that influence the coagulation cascade;
• Synthesis in the blood of bradykinin, a peptide responsible for the typical symptoms of inflammation, such as swelling, redness, heat and pain;
• PAF (platelet-activating factor), which creates inflammatory effects through narrowing of the blood vessels and constriction of the airways, but also through the degranulation of leukocytes.

The symptoms of endotoxemia are:  hypotension, metabolic acidosis, hemoconcentration, intestinal hemorrhage, fever, activations of neutrophils and endothelial cells, and predisposition to thrombosis.

In case of a progression to septic shock, the following sequence takes place:

1) Reduction in blood pressure and increased heart rate (hemodynamic alterations)

2) Abnormalities in body temperature

3) Progressive hypoperfusion at the level of the microvascular system

4) Hypoxic damage to susceptible cells

Up to here, symptoms follow a (severe) endotoxemia pathogenesis. A septic shock furthermore entails:

5) Quantitative changes in blood levels of leukocytes and platelets

6) Disseminated intravascular coagulation (see Hageman factor)

7) Multi-organ failure

8) Death of animal

If an animal is continously challenged with endotoxins, experiences septic shock, or comes close to it, it risks developing LPS tolerance, also known as CARS (compensatory anti-inflammatory response syndrome). This syndrome essentially depresses the immune system to control its activity. The anti-inflammatory prerogative of CARS is not to interfere directly with the elimination of pathogens but to regulate the “excessive” inflammatory reaction in a hemostatic way. However, this regulation can be extremely dangerous as the syndrome involves a lack of homeostasis control, and an excessive depression of the immune system leaves the organism exposed to the actual pathogens.

Farm animal research on endotoxemia pathogenesis

Lipopolysaccharides are difficult to quantify in the intestine of a live animal. One way to evaluate a possible endotoxemia is to analyze biomarkers present in the bloodstream. The most important one is the LPS themselves, which can be detected in a blood sample taken from the animal via ELISA. Other biomarkers include pro-inflammatory interleukins, such as TNF α and β, IL-6 or IL-8, and fibrin and fibrinogen (though they are not specific to endotoxemia). It is vital to carry out a blood sample analysis to deduce a possible endotoxemia from symptoms and performance losses in the animal.

How the metabolic effects of endotoxemia depress performance

One of the biggest issues caused by endotoxemia is that animals reduce their feed intake and show a poor feed conversion rate (FCR). Why does this happen? The productive performance of farm animals (producing milk, eggs, or meat) requires energy. An animal also requires a certain baseline amount of energy for maintenance, that is, for all activities related to its survival. As a result of inflammation and all those physiological reactions mentioned above, endotoxemia leads to a feverish state. Maintenance needs to continue; hence, the energy required for producing heat will be diverted from the energy usually spent on producing milk, egg, meat, etc., and performance suffers.

The inflammation response can result in mitochondrial injury to the intestinal cells, which alter the cellular energy metabolism. This is reflected in changes to the levels in adenosine triphosphate (ATP), the energy “currency” of living cells. A study by Li et al. (2015) observed a respective reduction of 15% and 55% in the ATP levels of the jejunum and ileum of LPS-challenged broilers, compared to the unchallenged control group. This illustrates the extent to which animals lose energy while they experience (more or less severe) endotoxemia.

Figure 3: Reduction in ATP level in Jejunum and Ileum in broilers (adapted from Li et al., 2015)

A piglet study by Huntley, Nyachoti, and Patience (2017) took this idea further (Figure 4):  3 groups of 10 Yorkshire x Landrace pigs, weighing between 11 and 25 kg, were studied in metabolic cages and in respiratory chambers. This methodology allows for simultaneous measurement of oxygen consumption, CO₂ production, energy expenditure, physical activity, and feed/water intake. The study found that LPS-challenged pigs retained 15% less of the available metabolizable energy and showed 25% less nutrient deposition. These results show concrete metabolic consequences caused by the febrile response to endotoxemia we discussed above.

Figure 4: Retained Energy as % of ME intake and nutrient deposition of pigs in metabolic cages (adapted from Huntley, Nyachoti, and Patience, 2017)

Control treatment (CON) = Pigs fed by a basal diet
Immune system stimulation treatment (ISS) = Pigs given LPS (E. coli serotype 055:B5) injection

A loss of energy retained due to a reduction in available metabolizable energy leads to losses in performance as the amount of energy available for muscle production and fat storage will be lower. Furthermore, the decrease in feed intake creates a further energy deficit concerning production needs.

A trial carried out at the University of Illinois examined the effects of repeated injections of 400 μg E. coli LPS on chick performance from 11 to 22 days after hatching. The chicks were fed casein-based diets with graded levels of arginine. LPS administration reduced weight gain (P<0.05) and feed intake, and these effects tended to be worse at higher levels of arginine supplementation (Figure 5). The researchers hypothesize that, in response to endotoxin and elevated cytokine levels, macrophages use more arginine to produce nitric oxide, diverting it from protein production for muscle development.

Figure 5: Effects of LPS on feed intake and body weight gain in chicks fed graded level of arginine (based on Webel, Johnson, and Baker, 1998)

NC = negative control

This data on poultry complements the results for swine, again showing that endotoxin-induced energy losses quantifiably depress animal performance even in milder disease cases.

The way forward: Endotoxin mitigation

Animals suffering from endotoxemia are subject to severe metabolic dysfunctions. If they do not perish from septic shock, they are still likely to show performance losses. Moreover, they at great risk of immunosuppression caused by the immune system “overdrive.” Effective endotoxin mitigating agents can help to prevent these scenarios.

EW Nutrition’s Mastersorb Gold is not only a leading anti-mycotoxin agent; thanks to its specific components, it effectively binds bacterial toxins. An in vitro study conducted at the Hogeschool Utrecht laboratory (part of Utrecht University) evaluated the binding capacity of Mastersorb Gold on LPS compared to three different competitor products. All products were tested at two different inclusion rates. At an inclusion rate of 0.25%, only Mastersorb Gold reduced the toxin load on the solution by 37%. At 1% inclusion, Mastersorb Gold bound 75% of the toxin, while only one competitor product demonstrated any binding (10%).

Figure 6: LPS adsorption capacity (%) – Mastersorb Gold clearly outperforms other anti-endotoxin products

Lipopolysaccharides are a constant challenge for animal production. The quantity of Gram-negative bacteria in an animal intestine is considerable; therefore, the danger of immune system over-stimulation through endotoxins cannot be taken lightly. Producers need to prioritize the maintenance of intestinal eubiosis in production animals proactively; for instance, through targeted gut health-enhancing additives based on phytomolecules and, possibly, organic acids.

Most importantly, the detrimental impact of LPS can be mitigated by using a high-performance agent such as Mastersorb Gold. To limit losses from an energy point of view yields positive results in terms of production levels and the prevention of secondary infections, preserving animal health and farms’ economic viability.

References

Adib-Conquy, Minou, and Jean-Marc Cavaillon. “Compensatory Anti-Inflammatory Response Syndrome.” Thrombosis and Haemostasis 101, no. 01 (2009): 36–47. https://doi.org/10.1160/th08-07-0421.

Huntley, Nichole F., C. Martin Nyachoti, and John F. Patience. “Immune System Stimulation Increases Nursery Pig Maintenance Energy Requirements.” Iowa State University Animal Industry Report 14, no. 1 (2017). https://doi.org/10.31274/ans_air-180814-344.

Li, Jiaolong, Yongqing Hou, Dan Yi, Jun Zhang, Lei Wang, Hongyi Qiu, Binying Ding, and Joshua Gong. “Effects of Tributyrin on Intestinal Energy Status, Antioxidative Capacity and Immune Response to Lipopolysaccharide Challenge in Broilers.” Asian-Australasian Journal of Animal Sciences 28, no. 12 (2015): 1784–93. https://doi.org/10.5713/ajas.15.0286.

Mani, Venkatesh, James H Hollis, and Nicholas K Gabler. “Dietary Oil Composition Differentially Modulates Intestinal Endotoxin Transport and Postprandial Endotoxemia.” Nutrition & Metabolism 10, no. 1 (2013): 6. https://doi.org/10.1186/1743-7075-10-6.

Webel, D.M., R.W. Johnson, and D.H. Baker. “Lipopolysaccharide-Induced Reductions in Body Weight Gain and Feed Intake Do Not Reduce the Efficiency of Arginine Utilization for Whole-Body Protein Accretion in the Chick.” Poultry Science 77, no. 12 (1998): 1893–98. https://doi.org/10.1093/ps/77.12.1893.

Zachary, James F. “Chapter 4 – Mechanisms of Microbial Infections.” Essay. In Pathologic Basis of Veterinary Disease, 132–241. St Louis, MO: Mosby, 2017. https://doi.org/10.1016/B978-0-323-35775-3.00004-7.

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

Arenas, Jesús, Ruth Bossers-De Vries, José Harders-Westerveen, Herma Buys, Lisette M. F. Ruuls-Van Stalle, Norbert Stockhofe-Zurwieden, Edoardo Zaccaria, et al. “In Vivo Transcriptomes of Streptococcus Suis Reveal Genes Required for Niche-Specific Adaptation and Pathogenesis.” Virulence 10, no. 1 (2019): 334–51. https://doi.org/10.1080/21505594.2019.1599669.

Brockmeier, Susan L. “Appendix F – The role of concurrent infections in predisposing to Streptococcus suis and other swine diseases: Proceeding from the 4th International Workshop on S. suis.” Pathogens 9, no. 5 (2020): 374. https://doi.org/10.3390/pathogens9050374.

Correa-Fiz, Florencia, José Maurício Gonçalves Dos Santos, Francesc Illas, and Virginia Aragon. “Antimicrobial Removal on Piglets Promotes Health and Higher Bacterial Diversity in the Nasal Microbiota.” Scientific Reports 9, no. 1 (2019): Article number: 6545. https://doi.org/10.1038/s41598-019-43022-y.

De Greeff, Astrid, Xiaonan Guan, Francesc Molist, Manon Houben, Erik van Engelen, Ton Jacobs, Constance Schultsz et al. “Appendix A – Streptococcus suis serotype 9 infection: Novel animal models and diagnostic tools: Proceeding from the 4th International Workshop on S. suis.” Pathogens 9, no. 5 (2020): 374. https://doi.org/10.3390/pathogens9050374.

Ferrando, M. Laura, Peter Van Baarlen, Germano Orrù, Rosaria Piga, Roger S. Bongers, Michiel Wels, Astrid De Greeff, Hilde E. Smith, and Jerry M. Wells. “Carbohydrate Availability Regulates Virulence Gene Expression in Streptococcus Suis.” PLoS ONE 9, no. 3 (2014). https://doi.org/10.1371/journal.pone.0089334.

Ferrando, Maria Laura, and Constance Schultsz. “A Hypothetical Model of Host-Pathogen Interaction OfStreptococcus Suisin the Gastro-Intestinal Tract.” Gut Microbes 7, no. 2 (2016): 154–62. https://doi.org/10.1080/19490976.2016.1144008.

Gebhart, Connie. “Cracking the Streptococcus Suis Code.” Pijoan Lecture. Lecture presented at the University of Minnesota Allen D. Leman Swine Conference, 2019. https://drive.google.com/file/d/1-E5tgFbteuPcDnMquOj_YhSKHYlaCqwO/view.

Goyette-Desjardins, Guillaume, Jean-Philippe Auger, Jianguo Xu, Mariela Segura, and Marcelo Gottschalk. “Streptococcus Suis, an Important Pig Pathogen and Emerging Zoonotic Agent—an Update on the Worldwide Distribution Based on Serotyping and Sequence Typing.” Emerging Microbes & Infections 3, no. 1 (2014): 1–20. https://doi.org/10.1038/emi.2014.45.

Haas, B., and D. Grenier. “Understanding the Virulence of Streptococcus Suis : A Veterinary, Medical, and Economic Challenge.” Médecine et Maladies Infectieuses 48, no. 3 (2018): 159–66. https://doi.org/10.1016/j.medmal.2017.10.001.

Murase, Kazunori, Takayasu Watanabe, Sakura Arai, Hyunjung Kim, Mari Tohya, Kasumi Ishida-Kuroki, Tấn Hùng Võ, et al. “Characterization of Pig Saliva as the Major Natural Habitat of Streptococcus Suis by Analyzing Oral, Fecal, Vaginal, and Environmental Microbiota.” Plos One 14, no. 4 (2019). https://doi.org/10.1371/journal.pone.0215983.

O’Dea, Mark A., Tanya Laird, Rebecca Abraham, David Jordan, Kittitat Lugsomya, Laura Fitt, Marcelo Gottschalk, Alec Truswell, and Sam Abraham. “Examination of Australian Streptococcus Suis Isolates from Clinically Affected Pigs in a Global Context and the Genomic Characterisation of ST1 as a Predictor of Virulence.” Veterinary Microbiology 226 (2018): 31–40. https://doi.org/10.1016/j.vetmic.2018.10.010.

Segura, Mariela, Nahuel Fittipaldi, Cynthia Calzas, and Marcelo Gottschalk. “Critical Streptococcus Suis Virulence Factors: Are They All Really Critical?” Trends in Microbiology 25, no. 7 (2017): 585–99. https://doi.org/10.1016/j.tim.2017.02.005.

Segura, Mariela, Virginia Aragon, Susan Brockmeier, Connie Gebhart, Astrid Greeff, Anusak Kerdsin, Mark O’Dea, et al. “Update on Streptococcus Suis Research and Prevention in the Era of Antimicrobial Restriction: 4th International Workshop on S. Suis.” Pathogens 9, no. 5 (2020): 374. https://doi.org/10.3390/pathogens9050374.

Tenenbaum, Tobias, Tauseef M Asmat, Maren Seitz, Horst Schroten, and Christian Schwerk. “Biological Activities of Suilysin: Role InStreptococcus Suispathogenesis.” Future Microbiology 11, no. 7 (2016): 941–54. https://doi.org/10.2217/fmb-2016-0028.

Valentin-Weigand, Peter, Fandan Meng, Jie Tong, Désirée Vötsch, Ju-Yi Peng, Xuehui Cai, Maren Willenborg et al. “Appendix G – Viral coinfection replaces effects of suilysin on adherence and invasion of Streptococcus suis into respiratory epithelial cells grown under air–liquid interface conditions: Proceeding from the 4th International Workshop on S. suis.” Pathogens 9, no. 5 (2020): 374. https://doi.org/10.3390/pathogens9050374.

Wells, Jerry, Virginia Aragon, and Paul Bessems. “Report on the deep analysis of the microbiota composition in healthy and S. suis-diseased piglets.” European Commission Program for Innovative Global Prevention of Streptococcus suis. Ref. Ares(2019)6305977, 2019. https://cordis.europa.eu/project/id/727966/results

Xia, Xiaojing, Wanhai Qin, Huili Zhu, Xin Wang, Jinqing Jiang, and Jianhe Hu. “How Streptococcus Suis Serotype 2 Attempts to Avoid Attack by Host Immune Defenses.” Journal of Microbiology, Immunology and Infection 52, no. 4 (2019): 516–25. https://doi.org/10.1016/j.jmii.2019.03.003.

Zeineldin, Mohamed, Brian Aldridge, and James Lowe. “Antimicrobial Effects on Swine Gastrointestinal Microbiota and Their Accompanying Antibiotic Resistome.” Frontiers in Microbiology 10 (2019). https://doi.org/10.3389/fmicb.2019.01035.

Zimmerman, Jeffrey J., Locke A. Karriker, Alejandro Ramirez, Kent J. Schwartz, Gregory W. Stevenson, and Jianqiang Zhang. Diseases of Swine. 11th ed. Hoboken, NJ: Wiley-Blackwell, 2019.

The global swine industry is going through unprecedented challenges. On the one hand, the threat of the African Swine Fever virus is global, despite the fact it hasn’t arrived in all markets. The virus is today alive among the wild boars in the Polish and Belgian forests. Every day it keeps gaining a few more meters to the border, threatening the German swine industry, one of the largest in the European Union.

If this happens, we might be seeing important changes to the pork supply chain on the meat market worldwide – in Europe in addition to current issues in the USA meat plants. The profitability of swine businesses depends in many ways on the export capacity of large corporations based in Germany, Spain, Denmark, etc.

On the other hand, the presence of COVID-19 in most countries is changing human behavior, meat consumption at home, and the way we look at the future. Perhaps a virus overload via the news, some “fake news” conveying wrong messages on what’s coming, and suddenly we feel the future will never be the same.

The future of the swine industry

At least for the swine industry, the future will indeed never be exactly the same. We will be facing different challenges. Some of these will be structural, such as the issue of decreased manpower and how to substitute manpower by machines, through the implementation of Precision Livestock Farming, for instance.

We are also facing important health challenges to our animals: not just ASF, but also new and more aggressive PRRS strains, among other pathogens. Our sows´ production capacity is increasing annually, yet in some cases 25% of the new-born piglets are lost from birth to market. Increasingly, we may start to see increased levels of mortality not only in the nursery but in fattening pigs and sows as well.

It is becoming clearer all the time: the future of the global swine industry lies in producing more pigs with reduced antibiotics. To stay the course, we need to take further action and implement corrective measures.

Why we should remove antibiotics in pig production

Pressure from stakeholders and regulators

There is, and there will be, increasing pressure from many stakeholders worldwide to work toward pig production with reduced or no antibiotics. Meat suppliers, slaughterhouses and processors, governments at different levels, and, of course, the European Union – all are demanding reductions in the level of antibiotics in livestock production.

There is also an increasing awareness at the global societal level regarding antimicrobial resistance related to antibiotic usage in farming production. Consumer pressure will grow exponentially as the terrible COVID-19 experience will be “digested” by the global population.

Pressure to accede to the pork market

There is yet another important reason to start working in that direction: the global swine meat market. Today, China’s pork meat shortage is opening the market. Now any producer could potentially sell meat, either to China or to any other country. We are starting to see moves from companies in the USA or Brazil banning the use of Ractopamine in their operations because they want to get access to the ractopamine-free market (Europe & Asia, over 70% of the global population).

According to M. Pierdon (AASV 2020 Proceedings), there will be two types of markets: the “Niche ABFree” and the “Commodity ABFree”. Companies will have to analyse what their future is on the meat market. Not all the producers may be willing to enter this new phase, but for sure many will try.

Strategies for antibiotic reduction

In Europe, the time has arrived. Zinc oxide will be banned in June 2021 and there is now more than a trend in production with less or no antibiotic use. In some cases, there is a need; in others, this is simply profitable.

Challenges to antibiotic reduction

Producing pigs completely without antibiotics is not easy, and not affordable for all. Initially we may have to give up some performance parameters in order to achieve the balance between what we want and what we can achieve in animal performance. But the time will arrive when these two objectives will converge; there is no alternative.

To that end, we will have to include in our pig production strategy all the available tools and technologies: genetic selection, immunization against some key pathogens, environmental control (mandatory but often forgotten), early detection of diseases, etc.

In this new era we are entering, nutrition and feed additives will play a key role. It will be crucial to find solutions targeting the microbiome’s stabilization and diversification, creating and maintaining healthy farms and achieving all the performance parameters.

Do we have the tools for antibiotic reduction?

Even today there are companies able to produce completely antibiotic-free pigs – proof that yes, the tools are already in place.

Nevertheless, for most producers, the answer to – Can we produce without antibiotics? is most likely “probably not”. This will require a holistic approach, given the specific case of piglets.

The microbiome of the piglet is strongly influenced by birth and the subsequent weeks. What, then, are the elements that will be part of this new game that comprises a new approach?

• • The colostrum intake & the management of the piglets
  • Antibiotic usage and its influence on the gut
  • The piglets’ microbiome and its evolution during the periweaning period
  • The weaning process, appetite, and water intake
  • Zinc oxide removal and its influence on the microbiome
  • The immune system and the relationship with the GIT status
  • Inflammation and its modulation at the gut level
  • The health status and the effect on the concomitant infections: which ones are key and which ones are secondary pathogens
  • The all-important biosecurity, management, and hygiene

To summarize: there is no one tool, but rather a holistic approach to face this new challenge that the swine industry is facing nowadays. The answer is not a silver bullet, but a journey that we all must undertake.

Available in Spanish here.