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How can you compensate an activated immune system in piglets?

piglets suckling

by  Fellipe Freitas Barbosa, Team Lead Global Technical Management – Swine, EW Nutrition

As pig production specialists, we understand that our animals are under constant challenge during their life. Challenges can be severe or moderate, correlated to several factors – such as, for instance, stage of production, environment, and so on – but they will always be present. To be successful, we need to understand how to counter these challenges and support the healthy development of our pigs.

Animal issues of an activated immune system

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., 2016Bischoff, 2011Celi et al., 2017Jayaraman and Nyachoti, 2017Kogut and Arsenault, 2016Moeser et al., 2017Pluske, 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.

faulty grain storage
Figure 1. Grain storage in a home pig farm

 

faulty feed mixer maintenance
Figure 2. Feed mixer in a home mixer pig farm

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).

Pig weight (kg)

 

ISA* SID Lysine (%) SAA (%) SAA:Lys
9 High 1,34 0,64 0,48
Low 1,07 0,59 0,55
14 High 1,22 0,62 0,51
Low 0,99 0,57 0,58

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.

Parameters

 

ISA*
High Low
Feed intake (g/d) 674 833
Weight gain (g/d) 426 566
Available P (%) 0,45 0,65

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




Piglet Nutrition Scenarios for AGP Removal

piglets farm scaled

by Fellipe Freitas Barbosa, Global Technical Manager Swine, EW Nutrition

 

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

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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




How phytomolecules support antibiotic reduction in pig production

swine schmidtkord

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.

Corn is often contaminated with Aspergillus fungi that can produce poisonous mycotoxins

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).

Figure 1: The role of phytomolecules within EW Nutrition’s holistic Antibiotic Reduction program

 

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




Mind the immunity gap: egg immunoglobulins bolster piglets’ immune system

EW Nutrition article piglets 6

egg immunoglobulins bolster piglets’ immune system

In contrast to humans, piglets do not receive any maternal immunoglobulins via the placenta. It is therefore of vital importance for these young animals to receive maternal antibodies via the colostrum as soon as possible after birth. Otherwise, they are more vulnerable to illnesses in their early stages of life.

In this article, we look in-depth at how the immune system works and which role antibodies play in it.  We then consider why immunoglobulins from the egg (IgY) might potentially be a powerful tool for supporting young animals immunologically, allowing producers to maintain young animals’ health and to promote their performance.

How the immune system defends the body: three barriers

The immune system aims to prevent pathogens such as viruses, bacteria, and fungi from entering the body or to eliminate them when they have already entered. Furthermore, it seeks to prepare the body for quicker reactions, in case of subsequent infections, by building an immunological memory. Generally, in case of an attack by pathogens, there are three barriers against the “enemy” (Figure 1).

Figure 1: The three barriers of the immune response

First barrier: the immediate, physical defense upon contact with pathogens

The animal body has several anatomical features that prevent pathogens from entering in the first place, such as cilia and mucus. Skin, intestines and nose lining are colonized by a community of beneficial micro-organisms that form a physical barrier against pathogens. Other barriers include the urinary system, the acid pH of the stomach, as well as tears and saliva, which contain antibacterial lysozymes.

Second barrier: the unspecific, native defense that does most of the work

If the mechanical mechanisms of defense were not successful, the unspecific, innate immune defense enters into play (Murphy and Weaver, 2018, 47ff.). At this stage, the body needs to differentiate between “known” and “alien” agents, and between “potentially harmful” and “harmless” ones.

To identify alien, potentially harmful agents, the unspecific defense looks for so-called PAMPs (pathogen associated molecular patterns). These are general characteristics often displayed by pathogens, such as lipopolysaccharides in the bacterial membrane or double-stranded RNA in viruses. Everything that shows PAMPs is heavily targeted.

The unspecific defense can be further divided into the humoral and the cellular defense. The humoral defense consists of substances dissolved in the body fluids, such as enzymes, reactive oxygen compounds, signal molecules and a whole cascade of proteins. Some of these substances kill pathogens directly; others “mark” the pathogens and “call for” the help of leucocytes.

The cellular defense consists of different leucocytes, also known as white blood cells (because they do not contain any red hemoglobin). The main task of leucocytes is the defense of the body against pathogens, hence many leucocytes are capable of phagocytosis (the ingestion of other cells). To prevent phagocytes from accidentally ingesting the body’s own cells, these own cells are marked with the so-called major histocompatibility complex (MHC). This acts as a red flag, saying “I belong to the body!”.

The cellular defense consists of:

  • Neutrophil granulocytes (60-70% of the leucocytes), which mainly act against bacteria
  • Eosinophil and basophil granulocytes (1.5% of the leucocytes), which mainly act against parasites
  • Natural killer cells, which mainly act against viruses
  • Monocytes (3-8% of the leucocytes; they differentiate into macrophages and dendritic cells)

Figure 1: The three barriers of the immune response

 

The monocytes, as well as their macrophage and dendritic cell “offspring”, are the bridge to the next step, the specific defense. When these phagocytes digest pathogens, minuscule protein structures (antigens) of the pathogens remain. These antigens are unique to each pathogen. During a process called antigen presentation, the antigens are tied to the cell’s MHC and transported to the cell surface. This triggers the production of specific antibodies, the immune system’s third barrier.

Third barrier: the specific immune defense that creates antibodies and immunological memory

The specific (also called adaptive or acquired) immune response kicks in a few days after contact with specific pathogens and is mostly carried out by lymphocytes called T and B cells (Murphy and Weaver, 2018, 177ff.). They are active at the cellular and the humoral level, respectively.

T cells possess receptors on their surface through which they can recognize the antigens presented to them by phagocytes. What they do subsequently depends on the subtype of the T cell:

  • Cytotoxic T cells (CD8+) directly destroy the antigen-phagocyte-combination
  • T helper cells (CD4+) attract other cells that can destroy the pathogens (e.g. macrophages) and stimulate B cells to produce antibodies against them

B cells also possess receptors through which they can recognize antigens. Once they spot an antigen (and T helper cells “confirm” that an immune response is required), they divide and mature into so-called plasma cells. Plasma cells, in turn, secrete plenty of antibodies (or immunoglobulins) into the bloodstream and the lymphatic system. Antibodies are protein structures that lock onto and neutralize antigens through different mechanisms.

The chemical reaction between antibodies and antigens is the body’s most powerful immune response through which it can protect itself from pathogens and their toxins. Antibody production continues for several days to remove the antigens, and antibodies usually remain in circulation for a few months.

Moreover, certain T and B cells memorize the first attack of a pathogen and turn into memory cells. The T memory cells CD4+CD8+, for instance, match the antigens from certain past, latent, and particularly persistent viral infections. This immunological memory, created by acquired immunity, can be thought of as a library of antibodies that the body adds to whenever it deals with a new pathogen or receives a vaccine. In case of a subsequent contact with the pathogen, the right antibody “model” already exists and mass production can start up very quickly.

Why young animals’ immune defense is so vulnerable – and what IgY can do about that

Building one’s immunological memory takes time. A lot of new-born animals are in a vulnerable position: they have not had time yet to acquire immunity of their own, but they are also particularly fragile and susceptible to being attacked by commonly occurring pathogens such as corona and rotaviruses, E. coli and clostridia. The toxins that E. coli and clostridia, for instance, release, may cause diarrhea, edema, endotoxic shock, and even death.

To be protected during the first critical days of their lives, new-born animals thus need to receive a foundational stock of antibodies (passive immunity) from their mother. Humans receive maternal immunoglobulins via the placenta. Piglets, because a sow’s placenta is constructed differently, are dependent on receiving them through the colostrum after birth. If this is not the case – due to inadequate quantity or quality of the colostrum – they need to receive immune support in a different way.

Egg-yolk antibodies have been proposed as a powerful tool for supporting young animals during the critical period after birth. These special proteins support the colostrum supply and guarantee that every animal in the herd has some degree of protection. This protection mostly takes place in the gut. The IgY recognize and tie up pathogens and render them ineffective.

Trial: can egg immunoglobulins support piglet immunity?

In 2009, research at the National Veterinary Research Institute in Pulawy, Poland, was conducted to probe this hypothesis. The objective of the trial was to evaluate whether an oral application of egg immunoglobulins would have a quantifiable, positive influence on the immune system of the piglets. Different immunological parameters were measured, including different types of leucocytes.

Trial design

The test consists of 6 litters with 67 piglets in total divided into two groups. The control group (n=32) received the prophylaxis customary on the farm; the trial group (n=35) additionally received a product based on egg powder (EP)[1], applied at the inclusion rate recommended by the producer. Blood samples were taken on days 0 (before application of the product), 7, 14, and 28. They were analyzed with respect to the percentages of different types of lymphocytes.

Trial results

For the group receiving egg powder, the number of leucocytes in peripheral blood was significantly elevated compared to the control group on the 7th day of life (table 1). The amounts of lymphocytes and monocytes – indicators for the specific immunological defense – were also significantly increased on day 7, whereas the total amount of granulocytes – indicator for the innate, unspecific immune defense – remained constant. Hence, already during the first days, the piglets supplied with EP disposed of a higher level of adaptive (specific) immune defense, compared to the animals in the control group. In addition, there was a significant increase in the number of CD4-positive (CD4+) and CD4-CD8-double positive (CD4+CD8+) T cells in the EP group, compared to the control animals, indicating an active stimulation of the immune system.

Except for CD4+CD8+ T cells (which remained elevated in the EP group), on day 14, the differences in cellular immune response were no longer significant. This is most probably the case because by that time the immune system of the control group had activated its own protective response. The EP product therefore supported the young animals precisely when it was necessary, during the critical first days of life.

Table 1: Hematological parameters measured in piglets after prophylactic application of an egg powder based product (EP1)

1Ig-PRO P (EW Nutrition)

The improvement of immune status, as indicated by the presence of the specific immune cells, was confirmed by the results for the incidence of diarrhea and mortality (table 2). The animals of the control group showed a nearly 1.5 times higher incidence of diarrhea and a 1.6 times higher rate of mortality. Another explanation of these results could be the mode of action of egg immunoglobulins: by neutralizing the pathogens directly in the gut, they prevent them from causing diarrhea in the first place.

Table 2: Incidence of diarrhea and mortality

Frequency of diarrhoea and mortality of piglets

In conclusion, this trial demonstrates that immunoglobulins from eggs (IgY) effectively support the immune system of piglets during the critical period of the first days of life.
Thanks to the stimulation of the young animals’ specific immune defense and the direct neutralization of pathogens in the gut, the incidence of diarrhea – one of the main causes of losses during the first weeks of life – decreases. Hence, mind the immunity gap: providing piglets with a suitable egg powder based product sets them up for long-term health, growth, and performance.

By I. Heinzl and S. Regragui Mazili


References:

Foley, J. A., and D. E. Otterby. “Availability, Storage, Treatment, Composition, and Feeding Value of Surplus Colostrum: A Review 1, 2.” Journal of Dairy Science 61, no. 8, 1033-1060. doi.org/10.3168/jds.S0022-0302(78)83686-8.
Heinzl, Inge, and Fellipe Barbosa. “Egg Antibody Technology for Nursery Pig Application.” Swineweb.com. June 24, 2019. Accessed July 17, 2019. https://www.swineweb.com/mind-the-immunity-gap-egg-immunoglobulins-bolster-piglets-immune-system/.
Marquardt, Ronald R., L. Z. Jin, Jung-Woo Kim, Lin Fang, Andrew A. Frohlich, and Samuel K. Baidoo. “Passive Protective Effect of Egg-yolk Antibodies against Enterotoxigenic Escherichia Coli K88 Infection in Neonatal and Early-weaned Piglets.” FEMS Immunology and Medical Microbiology 23, no. 4 (1999): 283-288. https://doi.org/10.1111/j.1574-695X.1999.tb01249.x.
Murphy, Kenneth M., and Casey Weaver. 2018. Janeway Immunologie. 9th ed. Translated by Lothar Seidler. Berlin: Springer.
Nascimbeni, Michelina, Eui-Cheol Shin, Luis Chiriboga, David E. Kleiner, and Barbara Rehermann. “Peripheral CD4 CD8 T Cells Are Differentiated Effector Memory Cells with Antiviral Functions.” Blood 104, no. 2 (2004): 478-486. doi:10.1182/blood-2003-12-4395.
Yokoyama, Hideaki, Robert C. Peralta, Roger Diaz, Sadako Sendo, Yutaka Ikemori, and Yoshikatsu Kodama. “Passive Protective Effect of Chicken Egg Yolk Immunoglobulins.” Infection and Immunity 60, no. 3 (March 1992): 998-1007. https://iai.asm.org/content/iai/60/3/998.full.pdf.

 

 




Optimal conditions in the farrowing unit put piglets in pole position

EW Nutrition article sow and piglets 6

Optimal conditions in the farrowing unit put piglets in pole position

The most important parameters for a pig producer are the number of healthy pigs weaned/sow/year and their weaning weight. Due to improved genetics, it is possible today to find production systems that deliver more than 30 pigs weaned/sow/year. Strategies to increase sow productivity need to take into account the management, feeding, and health of both the piglets and the sows.

Pigs’ start in life – limited energy reserves and practically no immune protection

It is generally known that pigs are born physiologically immature. Their energy reserves are limited. They only possess 1-2 % fat, the main part of which is subcutaneous or structural fat protecting organs, joints and skin. Thus, the young pigs depend on the glucose of the glycogen deposits in the liver as main source of energy. This energy supply only meets their requirements for the first few hours.
Besides that, pigs cannot count on maternal antibodies. Unlike in humans, a sow’s placenta is not built to enable the transfer of these protective cells within the womb. At birth, the amount of protective cells in a pig’s intestine, the main site of pathogenic contamination, is therefore virtually zero. As they are born without any immune protection, new-born pigs rely on an early supply of antibodies from the maternal colostrum. During the first 24-36 hours after birth, antibodies are absorbed in the intestine and pass directly to the bloodstream. The intestinal barrier then closes. Importantly, the content of antibodies in the colostrum decreases with every hour after birth.

Prevention – the best way to protect the progeny!

Given this difficult situation in the early stages of life, it is clear that the farrowing unit should be as comfortable as possible for the young animals:

  • It should be warm, as low temperatures contribute to hypoglycemia. The search for body heat at the sow additionally increases the risk of crushing, one of the main causes of pig losses. The problem arising here is that sows and the new-born pigs have different temperature requirements. One good solution is a heat lamp, installed specifically for the piglets.
  • It should be clean, and pathogenic pressure should be as low as possible. Due to their poor immune status, young pigs are susceptible to diarrhea-causing pathogens like E. coli and Clostridium perfringens during their first days of life. In order to meet hygiene requirements, the first step is a careful cleaning and disinfection of the farrowing unit prior to placing the sows/gilts.

Sows’ manure – the first source of contamination

Cleaning both the farrowing unit and also the sows/gilts before placing them is helpful. Producers, however, have to understand that a sow is continuously shedding pathogens through her feces and that her young come into contact with them. In fact, sow manure is the first source of contamination for new-born pigs.
There are several methods to decrease pathogens within the sow’s gut. Feeding them natural substances such as probiotics or phytomolecules (also known as secondary plant compounds) in order to improve gut health is one possibility: beneficial microbes such as lactobacilli or bifidobacteria compete with pathogens such as E. coli or clostridia for nutrients and prevent their proliferation. Phytomolecules such as carvacrol and cinnamaldehyde, on the other hand, were found to have antimicrobial properties.
Could feeding them egg immunoglobulins be another possibility?

Egg immunoglobulins – the key to reduce pathogenic pressure?

Yokoyama et al. (1992 and 1997) already showed that immunoglobulins from eggs applied to piglets bind to pathogens within their intestinal tract. If they also bind pathogens in the sow’s gut – generating harmless complexes – this could be the key to reduce pathogenic pressure in the farrowing unit.

Trial

Method
To evaluate this possibility a trial was conducted in Japan. Two groups of eight sows were used. The sows of the control group received standard lactation feed. The trial group was also fed standard feed, but additionally received a supplement containing egg powder product (EPP) with immunoglobulins* at a dosage of 5g/sow twice daily during the last ten days before and the first seven days after delivery. The feces of the sows were obtained by rectal stimulation (in order to rule out contamination from the environment) on day 10 before and day 7 after delivery. The amount of colony-forming units (CFU) of total E. coli, E. coli O141 and Clostridium perfringens was determined.

Results
The results are shown in figure 1. At the beginning of the trial, before the application of the EPP, both groups showed nearly the same level of the pathogens evaluated, with a slight disadvantage for the EPP group. After 17 days of using the EPP, the sows of the EPP group showed lower levels of pathogens in their excrements than the sows of the control group. A reduction in the colony-forming units of total Escherichia coli (from 107.12 to 106.3), Escherichia coli O141 (from 106.8 to 105.6) and of Clostridium perfringens (from 105.17 to 104.24) could be seen.

*The product used in this trial was Globimax® Sow, EW Nutrition.

Egg immunoglobulins – a tool to optimize conditions in the farrowing unit

It is important for pig producers to understand how they can combat adverse influences on their animals’ performance. The results of this trial showed that supplementing the standard sows’ diets with the EPP substantially reduced the amount of pathogenic colonies in sow’s manure. Reducing pathogenic pressure in the farrowing unit is central to reducing the incidence of diarrhea and pre-weaning mortality. Giving young pigs the best possible start in life sets them up for delivering the best possible performance – and more healthy and heavy pigs weaned/sow/year means a more profitable farm.

Figure 1: Amounts of total E. coli, O 141 E. coli and Clostridium perfringens in the feces of sows 10 days before delivery (before the first application of EPP) and 7 days after delivery (after the last application of EPP)

 

By Inge Heinzl and Fellipe Barbosa


References:

Yokoyama, H., Peralta, R. C., Diaz, R., Sendo, S., Ikemori, Y. and Kodama, Y. (1992): Passive protective effect of chicken egg yolk immunoglobulins against experimental enterotoxigenic Escherichia coli infection in neonatal piglets. Infection and Immunity, March edition, 998-1007.
Yokoyama, H., Hashi, T., Umeda, K., Icatlo, F. C., Kuroki, M., Ikemori, Y. and Kodama, Y. (1997): Reduced intestinal colonization with F18-positive enterotoxigenic Escherichia coli in weaned pigs fed chicken egg antibody against the fimbriae. FEMS Immunology and Medical Microbiology (18), 153-161.

 

 




Why we need to replace zinc oxide in tackling post-weaning diarrhea

SOW Schmidtkord DSC2695 website

Piglets experience significant stress when they are weaned from the sow and change diet, making them susceptible to gastrointestinal disorders. Primarily during the first two weeks after weaning, they are likely to suffer from post-weaning diarrhea (PWD). PWD is a significant problem for pig producers worldwide: it leads to severe dehydration, stunted growth and mortality rates of up to 20-30%. Treatment and additional labor costs further squeeze farm profitability and necessitate unwanted antibiotic interventions.

Zinc oxide: an effective but highly problematic tool

Since the early 1990s zinc oxide (ZnO) has been used to control post-weaning diarrhea and promote growth in piglets, mainly at pharmacological dosages of 2500 to 3000ppm. Its mode of action is still not entirely understood; effects on immune or metabolic processes, altered microbiota, or post-absorptive metabolism are likely to play a role. What is clear is that the use of ZnO in European pig production has strongly increased since the EU banned the use of antibiotic growth promoters such as colistin in 2006 to curb the development of antimicrobial resistance.

Pigs depend on a continuous supply of zinc. Among other roles, this trace element constitutes a functional component of around 300 biochemical enzymes, making it pivotal to most metabolic processes, and by extension to optimal health, production and reproduction.  Modern pig diets thus include zinc supplementation to meet the animals’ requirements. The European Food Safety Authority (EFSA) currently suggests that a total level of 150ppm of zinc in feed matches the animals’ physiological need for zinc. The EFSAs concerns are solely connected to the environmental concerns arising from pharmacological high dosages of ZnO.

These concerns are grave indeed: zinc is a heavy metal after all. Too much zinc is toxic for the animal, hence its physiology ensures that excessive zinc intake is excreted. The bioavailability and absorption of zinc from zinc oxide is particularly low. Therefore most of the zinc given to piglets in this way accumulates in their manure – which is widely used as an organic fertilizer for agricultural soils.

The continual application of manure gradually increases topsoil zinc concentrations; leaching and run-off then lead to contamination of groundwater, surface waters, and sediment. As zinc is non-volatile and non-degradable, it is only a matter of time before concentrations lead to ecotoxic effects, including food crops, aquatic life, and drinking water. Classic mitigation measures such as diluting the manure or keeping certain minimum distances between application areas and surface waters can only slow down the environmental accumulation of zinc, not prevent it.

EU ban: ZnO to be phased out by 2022

In 2017, the European Medicines Agency (EMA) – the EU agency responsible for the scientific evaluation, supervision and safety monitoring of medicines, including veterinary medicinal products – conducted an overall risk-benefit analysis for ZnO. It concluded that the benefits of preventing diarrhea in pigs did not outweigh the significant environmental risks caused by zinc pollution. By June 2022 all EU member states will thus have to withdraw marketing authorizations for veterinary medicinal products containing zinc oxide that are administered orally to food-producing species.

In its decision, the EMA’s Committee for Medicinal Products for Veterinary Use also points out the risk that, due to co-resistance, the use of zinc oxide might promote the development of antimicrobial resistance. High doses of zinc supplementation have been shown to increase the proportion of multidrug-resistant E. coli and Salmonella, two of the most important pathogens in pig production.

What is more, studies show that excessive zinc can accumulate in the liver, the pancreas, and blood serum, and that it permanently reduces the lactobacilli population of the gut flora. With what consequences for performance in the fattening phase? Hence, there are plenty of reasons why getting rid of zinc oxide is a good thing and will ultimately result in even better, more sustainable pig production – but, of course, only if effective replacement strategies to control PWD and boost piglet performance are in place.

Towards zero ZnO: smart feed additives optimize gut health

The search for ZnO alternatives takes us right back to the start, to the piglets’ challenged gastrointestinal tract. During their first three months of life, pigs’ gastrointestinal system undergoes a complex maturation process of its epithelial, immune, and enteric nervous systems. Only once all of these systems are fully developed is the gut capable of delivering its normal functions (digestion, nutrient absorption, immunity, etc.), while also providing an effective barrier against the pathogens, antigens, and toxins in the lumen.

Unlike in nature, where weaning occurs around the time when GIT functions have matured, weaning in commercial pig production takes place during this vulnerable developmental period. Post-weaning diarrhea is ultimately a consequence of intestinal dysbiosis, a state of imbalance in the intestinal microbiome which in turn is induced by the dietary, behavioral, and environmental stressors of the weaning phase (such as separation from the sow, vaccinations, transport, introduction of solid feed).

PWD control thus starts with managing these stressors, which includes ensuring sufficient colostrum intake, gradual feed changes, and meticulous nursery hygiene. Critically, the weaning diet needs to optimally support gut health. Intelligent feed additive solutions are able to

  • reduce the pathogenic load in the piglet’s GIT,
  • strengthen the piglet’s maturing gut barrier functionality, and
  • selectively induce the development of beneficial microorganisms within the microbiome.

A synergistic combination of phytomolecules, medium-chain fatty acids, glycerides of butyric acid, and prebiotics achieves these objectives in a reliable and cost-effective manner. Thanks to their antimicrobial, anti-inflammatory, and digestive properties these selected ingredients effectively support piglets during this critical phase of their postnatal gut development, while also boosting their feed intake.

In the past decade, the European pig sector has successfully adapted to the 2006 ban on antibiotic growth promoters through significant improvements in management and feed practices. Cutting out zinc oxide is an ambitious challenge – but with the support of targeted, functional feed additives, producers will be able to set their piglets up for a strong, sustainable, zero ZnO health and growth performance.

*You can find this article in polish and italian.

References

Amezcua, Rocio, Robert M. Friendship, Catherine E. Dewey, Carlton Gyles, and John M. Fairbrother. “Presentation of postweaning Escherichia coli diarrhea in southern Ontario, prevalence of hemolytic E. coli serogroups involved, and their antimicrobial resistance patterns.” Canadian Journal of Veterinary Research 66, no. 2 (April 2002): 73-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC226986/.

Bednorz, Carmen, Kathrin Oelgeschläger, Bianca Kinnemann, Susanne Hartmann, Konrad Neumann, Robert Pieper, Astrid Bethe, et al. “The Broader Context of Antibiotic Resistance: Zinc Feed Supplementation of Piglets Increases the Proportion of Multi-Resistant Escherichia Coli in Vivo.” International Journal of Medical Microbiology 303, no. 6-7 (2013): 396–403. https://doi.org/10.1016/j.ijmm.2013.06.004.

Brugger, Daniel, and Wilhelm M. Windisch. “Strategies and Challenges to Increase the Precision in Feeding Zinc to Monogastric Livestock.” Animal Nutrition 3, no. 2 (March 24, 2017): 103–8. https://doi.org/10.1016/j.aninu.2017.03.002.

Burrough, Eric R., Carson De Mille, and Nicholas K. Gabler. “Zinc Overload in Weaned Pigs: Tissue Accumulation, Pathology, and Growth Impacts.” Journal of Veterinary Diagnostic Investigation 31, no. 4 (June 6, 2019): 537–45. https://doi.org/10.1177/1040638719852144.

De Mille, Carson, Emma T. Helm, Eric R. Burrough, and Nicholas K. Gabler. “Zinc oxide does not alter ex vivo intestinal integrity or active nutrient transport in nursery pigs.” Paper presented at the Zero Zinc Summit, Copenhagen, Denmark, June 17-18, 2019. https://svineproduktion.dk/Services/-/media/3E0A1D2A4CAC409FAA6212B91DFEA537.ashx.

Moeser, Adam J., Calvin S. Pohl, and Mrigendra Rajput. “Weaning Stress and Gastrointestinal Barrier Development: Implications for Lifelong Gut Health in Pigs.” Animal Nutrition 3, no. 4 (December 2017): 313–21. https://doi.org/10.1016/j.aninu.2017.06.003.

Rhouma, Mohamed, Francis Beaudry, William Thériault, and Ann Letellier. “Colistin in Pig Production: Chemistry, Mechanism of Antibacterial Action, Microbial Resistance Emergence, and One Health Perspectives.” Frontiers in Microbiology 7 (November 11, 2016): Article 1789. https://doi.org/10.3389/fmicb.2016.01789.

Starke, Ingo C., Robert Pieper, Konrad Neumann, Jürgen Zentek, and Wilfried Vahjen. “The Impact of High Dietary Zinc Oxide on the Development of the Intestinal Microbiota in Weaned Piglets.” FEMS Microbiology Ecology 87, no. 2 (February 1, 2014): 416–27. https://doi.org/10.1111/1574-6941.12233.

 

 

 




Understanding and managing Strep suis in swine: The essentials

shutterstock 281988731

Strep suis causes vast losses in pig production and threatens human health, too. We still rely on antibiotics to control it – but we will have to change tactics to contain antimicrobial resistance.

 

Streptococcus suis is one of the most economically harmful pathogens for the global swine industry. When I started working in pig production 25 years ago, S. suis was already a problem on practically all the farms that I visited. Back then, our understanding of the pathogen and hence our control strategies were rudimentary: in farrowing rooms, we cut piglets’ teeth, used gentian violet spray on their navels, and sometimes applied penicillin lyophilized with iron. For the nursery phase, we only had penicillin or phenoxymethylpenicillin at our disposal – until the first amoxicillin-based premixes arrived, which turned out to be highly effective.

To this day, we control S. suis mainly through oral beta-lactam antibiotics (in feed or water) or injectable solutions, administered to piglets at an early age. However, pig production has evolved dramatically over the past decades, and so has the scientific research on this complex pathogen. Crucially, we now know that the excessive use of antibiotics contributes to the development of antimicrobial resistance.

Recent Australian research has discovered S. suis strains (both in humans and pigs) with a high degree of resistance to macrolides or tetracyclines, strains with intermediate sensitivity to Florfenicol, and others that are developing resistance to penicillin G. Additionally, we now know that S. suis is a zoonotic bacteria that affects not only at-risk farm or slaughterhouse personnel: S. suis is among the leading causes of death from meningitis in countries such as Thailand, China or Vietnam. In light of these threats to human health, we in the swine industry more than ever have a duty to help control this pathogen.

This article first reviews our current state of knowledge about the epidemiology and pathogenesis of Strep suis; it then lays out virulence factors and the role of coinfections. The second part considers the dimensions of a holistic approach to S. suis prevention and control and highlights the central role of intestinal health management.

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.

piglets suckling

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.

Author: Rafa Pedrazuela, Global Technical Manager Swine – 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.

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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.

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Fewer pathogens with egg immunoglobulins

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Piglets nursing

For newborn pigs there are often a host of different challenges – think of crushing or contamination of the farrowing pen.
For the last problem, solutions exist. A dietary approach can help to relieve pathogenic pressure through sow manure.

The main objective of a piglet producer is to maximise the number of healthy weaned piglets per animal per year. Nowadays, it is not difficult to find production systems delivering more than 30 piglets weaned/sow/year. Combining strategies on management, feeding, and health of both piglets and sows, is crucial for increasing sow’s productivity. A unique environment that can determine the success of a piglet farm is the farrowing unit. It is important to reduce as much as possible losses during this period. Pre-weaning mortality must always be monitored and targets must be set. In European conditions, it ranges between 8-10%.

One important driver in reducing pre-weaning mortality is understanding the fragility of newborn piglets. At birth, the resources of a piglet are very scarce: low energy reserves and practically no immune defence against existing pathogens in their new environment. Problems are prone to happen and will be mostly caused by pathogens present in the environment, in the feed, in the water and most important, in the faeces of the sow. The main contamination source for newborn piglets is their mother’s manure. And this first contamination can be quite severe causing diarrhoea and increasing piglet mortality.

Together with crushing, diarrhoea definitely causes a high percentage of total losses during the first days of life. In most of the cases, the disease is caused not only by one agent but by a combination of enteric infections from different pathogens or at least different strains of a pathogenic species. E. coli and clostridia are two of the most important diarrhoea causing pathogens during the first weeks after birth.

Pathogens during the first days
E. coli is well known as one of the main responsible pathogens for pre-weaning diarrhoea. And although it belongs to the normal intestinal flora of pigs, part of the different E. coli strains are pathogenic. E. coli cause about 80% of diarrhoeas in piglets and 50% of losses in piglet production. The factors making E. coli pathogenic, the so-called virulence factors include e.g. fimbria to attach to the intestinal wall and the capacity to produce toxins.

The Clostridium species are another important pathogen class. During the suckling phase, piglets are quite susceptible to Clostridium perfringens type C. This bacteria causes necrotic enteritis in piglets and the clinical symptoms appear during the first days of life. This disease provokes serious disturbances in the organism with a mortality up to 100%. It causes significant decrease in daily gain and in weaning weight.

Strategy to protect the piglets
In order to maximise the sow’s performance – measured in piglets weaned per year – it is crucial to provide the best possible conditions to the piglets. Therefore the reduction of the pathogenic pressure in the farrowing unit ranks first. Cleaning of the pen is a way to get rid of germs like E. coli and Clostridium species, the most important pathogens during the first days. This should be completed by an effective gut health management in sow and piglets. For this purpose natural ingredients can be used. Supplying natural and active immune cells, the so called antibodies, has been proven to be quite efficient in supporting gut health. Applied to piglets, immunoglobulins from the egg bind to pathogens within the intestinal tract. They show efficiency in supporting piglets’ performance, decreasing the incidence of diarrhoea, mortality and increasing daily gain.

The idea was to check if these immunoglobulins from the egg could also bind pathogens in the sow’s gut and generate harmless complexes. That way pathogenic pressure for the piglets could be reduced. Thus a trial was conducted in Japan to check this thesis.

 

*Globigen Sow

Trial
In the trial two groups contained eight sows each. The sows of the control group received standard lactation feed, the trial group was also fed standard feed with a supplement containing egg immunoglobulins (Globigen Sow, EW Nutrition, at a dosage of 5 g/sow twice daily) on top during the last ten days before and the first seven days after delivery. The faeces of the sows were obtained by rectal stimulation (in order to get no contamination from the environment) on day 10 before and day 7 after delivery. The amount of colony forming units (CFU) of total E. coli, E. coli O141 and Clostridium perfringens were determined.

Results are shown in Figure 1. At the beginning of the trial, before the application of the immunoglobulin supplement, both groups showed nearly the same level of the evaluated pathogens with a slight disadvantage for the supplement group. After 17 days of applying the product based on egg immunoglobulins, a reduction of the colony forming units of total E. coli, E. coli O141 and of Clostridium perfringens could be seen. The sows of the supplement-fed group showed a lower level of pathogens in their excrements than the sows of the control group.

Conclusion
It is important for swine producers to understand what adversely influences the results on the farm. One consideration is to improve farrowing unit conditions of the piglets, aiming to reduce pre-weaning mortality. The results of the trial showed that a supplement based on egg immunoglobulins supplied on top of standard sow diets substantially reduced the amount of pathogenic colonies in sow manure. The reduction on pathogenic pressure and therefore the incidence of diarrhoea may be an alternative for increasing the profitability of piglet producers by increasing the number of healthier piglets weaned/sow/year.

*References are available on request.

By Dr Fellipe Barbosa & Dr Inge Heinzl.
Published on PigProgress | 20th July, 2018.