Organic acids can play a crucial role in zinc oxide replacement

Dr. Inge Heinzl, Editor EW Nutrition &
Juan Antonio Mesonero Escuredo, GTM Swine/GPM Organic Acids EW Nutrition

The use of high levels of Zinc Oxide (ZnO) in the EU before 2022 was one of the most common methods to prevent postweaning diarrhea (PWD) in pig production. Pharmacologically high levels of ZnO (2000-3000 ppm) increase growth and reduce the incidence of enteric bacterial diseases such as post-weaning diarrhea (PWD)( Carlson et al., 1999; Hill et al., 2000; Hill et al., 2001; Poulsen & Larsen, 1995; De Mille et al., 2019).

However, ZnO showed adverse effects, such as the accumulation of heavy metal in the environment, the risk for antimicrobial resistance (AMR), and problems of mineral toxicity and adverse growth effects when feeding it longer than 28 days (Jensen et al., 2018; Cavaco et al., 2011; Vahjen, 2015; Romeo et al., 2014; Burrough et al., 2019). To replace ZnO in pig production, let us first look at its positive effects to know what we must compensate for.

ZnO has a multifactorial mode of action

ZnO shows several beneficial characteristics that positively influence gut health, the immune system, digestion, and, therefore, also overall health and growth performance.

FigureFigure 1. Beneficial effects and ZnO mode of action in postweaning piglets

1.   ZnO acts as an antimicrobial

Concerning the antimicrobial effects of ZnO, different possible modes of action are discussed:

  • ZnO in high dosages generates reactive oxygen species (ROS) that can damage the bacterial cell walls (Pasquet et al., 2014)
  • The death of the bacterial cell due to direct contact of the metallic Zn to the cell (Shearier et al., 2016)
  • Intrinsic antimicrobial properties of the ZnO2+ ions after dissociation. The uptake of zinc into cells is regulated by homeostasis. A concentration of the ZnO2+ ions higher than the optimal level of 10-7 to 10-5 M (depending on the microbial strain) allows the invasion of Zn2+ ions into the cell, and the zinc starts to be cytotoxic (Sugarman, 1983; Borovanský et al., 1989).

ZnO shows activity against, e.g., Staphylococcus aureus, Pseudomonas aeruginosa, E. coli, Streptococcus pyogenes, and other enterobacteria (Ann et al., 2014; Vahjen et al., 2016). However, Roselli et al. (2003) did not see a viability-decreasing effect of ZnO on ETEC.

2.   ZnO modulates the immune system

Besides fighting pathogenic organisms as described in the previous chapter and supporting the immune system, ZnO is an essential trace element and has a vital role in the immune system. ZnO improves the innate immune response, increasing phagocytosis and oxidative bursts from macrophages and neutrophils. It also ameliorates the adaptative immune response by increasing the number of T lymphocytes (T cells) in general and regulatory T lymphocytes (T-regs) in particular. These cells control the immune response and inflammation (Kloubert et al., 2018). Macrophage capacity for phagocytosis (Ercan and Bor, 1991) and to kill parasites (Wirth et al., 1989), and also the killing activity of natural killer cells depends on Zn (Rolles et al., 2018). By reducing bacterial adhesion and blocking bacterial invasion, ZnO disburdens the immune system (Roselli et al., 2003).

ZnO reduces the expression of several proinflammatory cytokines induced by ETEC (Roselli et al., 2003). Several studies have also shown a modulation effect on intestinal inflammation, decreasing levels of IFN-γ, TNF-α, IL-1ß and IL-6, all pro-inflammatory, in piglets supplemented with ZnO (Zhu et al., 2017; Grilli et al., 2015).

3.   ZnO improves digestion and promotes growth

Besides protecting young piglets against diarrhea, the goal is to make them grow optimally. For this target, an efficient digestion and a high absorption of nutrients is essential. Stimulating diverse pancreatic enzymes such as amylase, carboxypeptidase A, trypsin, chymotrypsin, and lipase increases digestibility (Hedemann et al., 2006; Pieper et al., 2015). However, Pieper et al. (2015) also showed that a long-term supply of very high dietary zinc triggers oxidative stress in the pancreas of piglets.

By stimulating the secretion of ghrelin at the stomach level and thereby promoting the release of insulin-like growth factor (IGF-1) and cholecystokinin (CCK), ZnO enhances muscle protein synthesis, cell proliferation, and feed intake (Yin et al., 2009; MacDonald et al., 2000)).

The result of improved digestion is increased body weight and average daily gain, which can be seen, e.g., in a study by Zhu et al. (2017).

4.   ZnO protects the intestinal morphology

ZnO prevents the decrease of the trans-endothelial electrical resistance (TEER), usually occurring in the case of inflammation, by downregulating TNF-α and IFN-γ. TNF-α, as well as IFN-γ, increase the permeability of the epithelial tight junctions and, therefore, the intestinal barrier (Al-Sadi et al., 2009).

The enterotrophic and anti-apoptotic effect of ZnO is reflected by a higher number of proliferating and PCNA-positive cells and an increased mucosa surface in the ileum (higher villi, higher villi/crypt ratio)(Grilli et al., 2015). Zhu et al. (2017) also saw an increase in villus height in the duodenum and ileum and a decrease in crypt depth in the duodenum due to the application of 3000 mg of ZnO/kg. Additionally, they could notice a significant (P<0.05) upregulation of the mRNA expression of the zonula occludens-1 and occluding in the mucosa of the jejunum of weaned piglets.

In a trial conducted by Roselli et al. (2003), the supplementation of 0.2 mmol/L ZnO prevented the disruption of the membrane integrity when human Caco-2 enterocytes were challenged with ETEC.

5.   ZnO acts antioxidant

The antioxidant effect of ZnO was shown in a study conducted by Zhu et al., 2017. They could demonstrate that the concentration of malondialdehyde (MDA), a marker for lipid peroxidation, decreased on day 14 or 28, and the total concentration of superoxide dismutase (SOD), comprising enzymes that transform harmful superoxide anions into hydrogen peroxide, increased on day 14 (P<0.05). Additionally, Zn is an essential ion for the catalytic action of these enzymes.

Which positive effects of ZnO can be covered by organic acids (OAs)?

1.   OAs act antimicrobial

OAs, on the one hand, lower the pH in the gastrointestinal tract. Some pathogenic bacteria are susceptible to low pH. At a pH<5, the proliferation of, e.g., Salmonella, E. coli, and Clostridium is minimized. The good thing is that some beneficial bacteria, such as lactobacilli or bifidobacteria, survive as they are acid-tolerant. The lactobacilli, on their side, can produce hydrogen peroxide, which inhibits, e.g., Staphylococcus aureus or Pseudomonas spp. (Juven and Pierson, 1996).

Besides this more indirect mode of action, a more direct one is also possible: Owing to their lipophilic character, the undissociated form of OAs can pass the bacterial membrane (Partanen and Mroz, 1999). The lower the external pH, the more undissociated acid is available for invading the microbial cells. Inside the cell, the pH is higher than outside, and the OA dissociates. The release of hydrogen ions leads to a decrease in the internal pH of the cell and to a depressed cell metabolism. To get back to “normal conditions”, the cell expels protons. However, this is an energy-consuming process; longer exposure to OAs leads to cell death. The anion remaining in the cell, when removing the protons, disturbs the cell’s metabolic processes and participates in killing the bacterium.

These theoretical effects could be shown in a practical trial by Ahmed et al. (2014). He fed citric acid (0.5 %) and a blend of acidifiers composed of formic, propionic, lactic, and phosphoric acid + SiO2 (0.4 %) and saw a reduction in fecal counts of Salmonella and E. coli for both groups.

2.   OAs modulate the immune system

The immune system is essential in the pig’s life, especially around weaning. Organic acids have been shown to support or stimulate the immune system. Citric acid (0.5%), as well as the blend of acidifiers mentioned before (Ahmed et al., 2014), significantly increased the level of serum IgG. IgG is part of the humoral immune system. They mark foreign substances to be eliminated by other defense systems.

Ren et al. (2019) could demonstrate a decrease in plasma tumor necrosis factor-α that regulates the activity of diverse immune cells. He also found lower interferon-γ and interleukin (Il)-1ß values in the OA group than in the control group after the challenge with ETEC. This trial shows that inflammatory response can be mitigated through the addition of organic acids.

3.   OAs improve digestion and promote growth

In piglets, the acidity in the stomach is responsible for the activation and stimulation of certain enzymes. Additionally, it keeps the feed in the stomach for a longer time. Both effects lead to better digestion of the feed.

In the stomach, the conversion of pepsinogen to pepsin, which is responsible for protein digestion, is catalyzed under acid conditions (Sanny et al., 1975)group. Pepsin works optimally at two pH levels: pH 2 and pH 3.5 (Taylor, 1959). With increasing pH, the activity decreases; at pH 6, it stops. Therefore, a high pH can lead to poor digestion and undigested protein arriving in the intestine.

These final products of pepsin protein digestion are needed in the lower parts of the GIT to stimulate the secretion of pancreatic proteolytic enzymes. If they do not arrive, the enzymes are not activated, and the inadequate protein digestion continues. Additionally, gastric acid is the primary stimulant for bicarbonate secretion in the pancreas, neutralizing gastric acid and providing an optimal pH environment for the digestive enzymes working in the duodenum.

As already mentioned, the pH in the stomach influences the transport of digesta. The amount of digesta being transferred from the stomach to the small intestine is related to the acidity of the chyme leaving the stomach and arriving in the small intestine. Emptying of the stomach can only take place when the duodenal chyme can be neutralized by pancreatic or other secretions (Pohl et al., 2008); so, acid-sensitive receptors provide feedback regulation and a higher pH in the stomach leads to a faster transport of the digesta and a worse feed digestion.

4.   OAs protect the intestinal morphology

Maintaining an intact gut mucosa with a high surface area is crucial for optimal nutrient absorption. Research suggests organic acids play a significant role in improving mucosal health:

Butyric acid promotes epithelial cell proliferation, as demonstrated in an in vitro pig hindgut mucosa study (Sakata et al., 1995). Fumaric acid, serving as an energy source, may locally enhance small intestinal mucosal growth, aiding in post-weaning epithelial cells’ recovery and increasing absorptive surface and digestive capacity (Blank et al., 1999). Sodium butyrate supplementation at low doses influences gastric morphology and function, thickening the stomach mucosa and enhancing mucosal maturation and differentiation (Mazzoni et al., 2008).

Studies show that organic acids affect gut morphology, with a mixture of short-chain and mid-chain fatty acids leading to longer villi (Ferrara et al., 2016) and Na-butyrate supplementation increasing crypt depth and villi length in the distal jejunum and ileum (Kotunia et al., 2004). However, the villi length and mucosa thickness in the duodenum were reduced. Dietary sodium butyrate has been linked to increased microvilli length and cecal crypt depth in pigs (Gálfi and Bokori, 1990).

5.   OAs show antioxidant activity

The last characteristic, the antioxidant effect, cannot be provided at the same level as with ZnO; however, Zhang et al. (2019) attest to OAs a certain antioxidant activity. Oxalic, citric, acetic, malic, and succinic acids, which were extracted from Camellia oleifera, also showed good antioxidant activity in a trial conducted by Zhang et al. (2020).

Organic acids are an excellent tool to compensate for the ban on ZnO

The article shows that organic acids have similar positive effects as zinc oxide. They act antimicrobial, modulate the immune system, maintain the gut morphology, fight pathogenic microbes, and also act – slightly – antioxidant. Additionally, they have a significant advantage: they are not harmful to the environment. Organic acids used in the proper pH range and combination are good tools for replacing zinc oxide.

References on request




Acidifiers support piglets after weaning

8 piglet photo last page

By Dr. Inge Heinzl, Editor, EW Nutrition

In piglet production, high productivity, meaning high numbers of healthy and well-performing piglets weaned per sow and year, is the primary target. Diarrhea around weaning often gets in the way of achieving this goal.

Up to the ban of antibiotic growth promoters in 2006, antibiotics were often applied prophylactically to help piglets overcome this critical time. Zinc oxide (ZnO) application is another measure that cannot be used anymore to prevent piglet diarrhea. Effective alternatives are required.

Weaning – a critical point in piglets’ life

Weaning stress is well-known to have a negative impact on the balance of the intestinal microflora and gastrointestinal functions (Miller et al., 1985). Suckling piglets have a limited ability to produce hydrochloric acid, but nature has a solution to compensate for this inadequacy. The lactobacilli present in the stomach can use the lactose in the sow’s milk to produce lactic acid (Easter, 1988). In nature, the piglets would start to eat small amounts of solid feed at about three weeks when the sow’s milk production no longer covers their nutrient demand. By increasing the feed intake, the piglets stimulate hydrogen chloride (HCl) production in their stomachs.

In piglet production, where weaning occurs at three or four weeks of age, the piglets are still not eating considerable amounts of solid feed. It is often the case that 50 % of the piglets take feed at the earliest after 24 h, and 10 % accept the first feed only after 48 h (Brooks, 2001). Additionally, hard grains in the diet can physically damage the small intestine wall, reducing villus height and crypt depth (Kim et al., 2005).

Only a minor production of HCl, no more lactose supply for the lactobacilli, varying feed intake, and high buffering capacity of the feed lead to a pH of >5 in the stomach.

The higher stomach pH is partly responsible for problems after weaning

A pH higher than 5, besides causing direct effects on the microflora in the stomach, has consequences for the whole digestive tract and digestion.

A high pH is favorable for certain microorganisms, including coliforms (Sissons, 1989) and other acid-sensitive bacteria such as Salmonella typhimurium, Salmonella typhi, Campylobacter jejuni, and V. cholerae (Smith, 2003).

  1.  Lower activity of proteolytic enzymes

    In the stomach, the conversion of pepsinogen to pepsin, which is responsible for protein digestion, is catalyzed under acid conditions (Sanny et al., 1975). Pepsin works optimally at two pH levels: pH 2 and pH 3.5 (Taylor, 1959). With increasing pH, the activity decreases; at pH 6, it stops. Therefore, a high pH can lead to poor digestion and undigested protein arriving in the intestine. There, it can be used as “feed” for harmful bacteria, leading to their proliferation. Barrow et al. (1977) found higher counts of coliforms in piglets’ intestinal tract two days after weaning, while the number of lactobacilli was depressed.

    In the lower parts of the gastrointestinal tract (GIT), the final products of the pepsin protein digestion are needed to stimulate the secretion of pancreatic proteolytic enzymes. If no final products arrive, the enzymes are not activated, and the inadequate protein digestion continues. Additionally, gastric acid is the main stimulant for bicarbonate secretion in the pancreas, neutralizing gastric acid and providing an optimal pH environment for the digestive enzymes working in the duodenum.

  2. Expedited digesta transport

    The stomach pH also influences the transport of digesta. The acidity of the chyme leaving the stomach and arriving in the small intestine is decisive for the amount of digesta being transferred from the stomach to the small intestine. Acid-sensitive receptors provide feedback regulation to prevent the stomach from emptying until the duodenal chyme can be neutralized by pancreatic or other secretions (Pohl et al., 2008). Therefore, a higher pH in the stomach leads to a faster transport of the digesta, resulting in worse feed digestion.

  3. Proliferation of microorganisms

    A high pH is favorable for certain microorganisms, including coliforms (Sissons, 1989) and other acid-sensitive bacteria such as Salmonella typhimurium, Salmonella typhi, Campylobacter jejuni, and V. cholerae (Smith, 2003).

    Elevated stomach pH + incomplete immune system = diarrhea

Acidifiers can mitigate the adverse effects of weaning on piglets

To overcome this critical time of weaning and maintain performance, acidifiers can be a helpful tool. They improve gut health, stimulate immunity, and serve as nutrient sources – while also positively affecting feed and water hygiene.

What are acidifiers?

Acidifiers’ role in pig nutrition has evolved from feed preservatives to stomach pH stabilizers, compensating for young pigs’ reduced digestive capacity (Ferronato and Prandini, 2020). They are now used to replace antibiotic growth promoters and ZnO, which were applied for a long time to mitigate the negative effects of weaning.

In general, both organic and inorganic acids and their salts feature in animal nutrition. They can be added to the feed or the water.

Organic acids: Commonly used with good results

Feed acidifiers are usually organic acids, including fatty and amino acids. Their carboxyl functional group is responsible for their acidic specificity as feed additives (Pearlin et al.,2019). Their pKa, the pH where 50 % of the acid occurs in a dissociated form, is decisive for their antimicrobial action. In animal nutrition, acids with pKa 3-5 are typically used (Kirchgeßner and Roth, 1991).

Organic acids used as feed additives can be divided into three groups:

  •  Simple monocarboxylic acids such as formic, acetic, propionic, and butyric acid
  •  Carboxylic acids with a hydroxyl group such as lactic, malic, tartaric, and citric acid
  • Short-chain carboxylic acids with double bonds – fumaric and sorbic acid.

The primary acids for pig nutrition are acetic, fumaric, formic, lactic, benzoic, propionic, sorbic, and citric acids (Roth and Ettle, 2005).

Inorganic acids – the low-cost version

Inorganic acids are cheaper than organic acids, but their only effect is to decrease the pH. Additionally, they are extremely corrosive and dangerous liquids due to their strong acidity in a pure state (Kim et al., 2005).

Salts are easier to handle

The advantage of salts over free acids is that they are generally odorless and easier to handle in the feed manufacturing process due to their solid and less volatile form. Higher solubility in water is a further advantage compared to free acids (Huyghebaert and Van Immerseel, 2011; Roth and Ettle, 2005; Partanen and Mroz, 1999). The better handling and higher palatability make acid salts a more user-friendly method to apply acids to feed and water without compromising their efficacy (Luise et al., 2020).

The salts are mainly produced with calcium, potassium, and sodium. They include calcium formate, potassium diformate, sodium diformate, and sodium fumarate.

Blends

A mixture of diverse acidifiers combines the different characteristics of these substances. Perhaps, there may be synergistic effects. Acid blends are more and more used as feed additives. They have a wider-ranging action than single substances.

Roth et al. (1996) showed that a combination of formic acid with various formats is more effective than the application of formic acid alone.

The main effects of acidifiers

Acidifiers support piglets during the critical time after weaning through different modes of action. The final results are:

  • Improvement in gut health
  • Increase in growth performance
  • Stabilization of the immune system.

1.    Improvement in gut health

As shown in figure 1, the improvement in gut health relies on the antimicrobial effect of organic acids and the decrease in the stomach’s pH.

1.1     Organic acids directly attack bacteria

Organic acids not only act through their pH-decreasing effect but also directly attack pathogens. Due to their lipophilic character, organic acids can pass the bacterial cell membrane when they are in their undissociated form (Partanen in Piva et al., 2001). The lower the external pH, the more undissociated acid can pass the membrane.

Within the cell, the pH is higher. Hence, the organic acid dissociates and releases hydrogen ions, reducing the cytoplasmic pH from alkaline to acid. Cell metabolism is depressed at lower pH. Therefore, the bacterial cell needs to expel protons to get the cytoplasmic pH back to normal. As this is an energy-consuming process, more prolonged exposure to organic acids kills the bacterium. Additionally, the anions staying within the cell disturb the cell’s metabolic processes and participate in killing the bacterium.

Studies from Van Immerseel et al. (2006) revealed that many fermentative bacteria could let their intracellular pH decline and prevent increased acid penetration. Bacteria with a neutrophil pH, however, react more sensitively.

1.1     Decreased pH reduces non-acid-tolerant pathogens

There is a direct effect of pH on the microflora. Some pathogenic bacteria are susceptible to low pH. The proliferation of, e.g., E. coli, Salmonella, and Clostridium perfringens is minimized at a pH<5. Acid-tolerant bacteria such as lactobacilli or bifidobacteria, however, survive. Many lactobacilli can produce hydrogen peroxide, which inhibits, e.g., Staphylococcus aureus or Pseudomonas spp. (Juven and Pierson, 1996).

 

Already Fuller (1977) showed in in vitro experiments that certain bacteria such as Streptococci, Salmonella, and B. cereus don’t grow in an environment with pH 4.5 or even die (Micrococcus). In contrast, Lactobacilli are not so susceptible to this low pH. Using the same binding sites as harmful bacteria, they suppress coliforms, for example. Kirchgeßner et al. (1997) found a stronger reduction of E. coli than Lactobacilli and Bifidobacteria in different gut segments when exposed to 1.25 % formic acid.

1.2     Recovery of eubiosis through reduction of substrate

The reduction of the pH through organic acids maintains or stimulates the secretion of proteolytic enzymes in the stomach (pepsin) and pancreatic enzymes. Additionally, the acid leaving the stomach is partly responsible for regulating gastric emptying (Ravindran and Kornegay, 1993; Mayer, 1994). Both effects by improving protein digestion, reduce the fermentable substrates arriving in the hindgut. This decreases the quantity of fermentable substrate arriving in the intestine and, therefore, the growth of undesired pathogens.

2. Promotion of growth

2.1     Enhanced digestion of macronutrients

As explained above, the acidity in the stomach is responsible for the activation and stimulation of enzymes. Additionally, the lower pH keeps the feed in the stomach for longer. Both result in better digestion.

The improved utilization of nutrients leads to higher daily gain and better feed conversion. In pigs, the growth-promoting effect of organic acids is particularly pronounced during the first few weeks after weaning (Roth and Ettle, 2005). Some examples of the growth-promoting effect of formic and propionic acid feature in table 1.

Table 1: Influence of two commonly used organic acids in animals on growth performance

Varying results are mainly due to the character of the organic acid, the dosage, the buffering capacity, and the possible reduction of feed intake in case of a high dosage (Roth and Ettle, 2005).

2.2     Improved utilization of minerals

Minerals are essential for metabolic processes and, thus, healthy growth. Chelated minerals show a higher digestibility. Acidic anions of the acidifiers form complexes (chelates) with cationic minerals such as Ca, Zn, P, and Mg. The resulting higher digestibility and absorption lead to decreased excretion of supplemented minerals and, therefore, to a lower environmental burden. Kirchgeßner and Roth (1982), e.g., reported an improved absorption and retention of Ca, P, and Zn with the addition of fumaric acid. However, there are also trials showing no effect of acidification of the diet on mineral balance (Radecki et al., 1988).

Phytic acid

Another factor influencing the absorption of minerals, mainly phosphorus, is the amount of intrinsic or microbial phytase in the diet (Rutherfurd et al., 2012). The enzyme phytase releases phosphorus out of phytic acid and increases its bioavailability. Partanen and Mroz (1999) showed that organic acids improve the performance of phytase and, therefore, the bioavailability of phosphorus in the diet.

Besides a better utilization by the animal, improved absorption of minerals means preserving the environment and direct cost-saving, as mineral supplements are expensive.

2.3     Stimulation of gut and stomach mucosal morphology

An intact gut mucosa with a preferably high surface is vital for efficient nutrient absorption. Many trials show that organic acids improve the condition of the mucosa:

Organic acids stimulate cell proliferation

In an in vitro trial with pig hindgut mucosa, butyric acid stimulated epithelial cell proliferation in a dose-dependent manner (Sakata et al., 1995).

Blank et al. reported that fumaric acid, being a readily available energy source, may have a local trophic effect on the small intestines’ mucosa. Due to faster recovery of the gastrointestinal epithelial cells after weaning, this trophic effect may increase the absorptive surface and digestive capacity in the small intestines.

Organic acids influence villi length and crypt depth in the gut

Ferrara et al. (2016) observed a trend toward longer villi with a mixture of short-chain organic acids and mid-chain fatty acids, compared to the negative control.

The addition of Na-butyrate to the feed leads to increased crypt depth, villi length, and mucosa thickness in the distal jejunum and ileum, according to Kotunia et al. (2004). However, the villi length and mucosa thickness were reduced in the duodenum.

According to Gálfi and Bokori (1990), a diet with 0.17% sodium butyrate increased the length of ileal microvilli and the depth of caecal crypts in pigs weighing between 7 and 102 kg.

Organic acids strengthen stomach mucosa

Mazzoni et al. (2008) reported that sodium butyrate applied orally at a low dose influenced gastric morphology and function (thickening the mucosa), presumably due to its action on mucosal maturation and differentiation.

2.4    Pigs can use organic acids acid as an energy source

Organic acids are usually added to the feed in small doses. As some organic acids are intermediary products of the citric acid cycle, they are an energy source after being absorbed through the gut epithelium by passive diffusion. Their gross energy can be fully metabolized (Pearlin et al., 2019; Roth and Ettle, 2005; Suiryanrayna and Ramana, 2015).

The gross energy supply varies according to the acid. Roth and Ettle (2005) determined values between 6 kJ/g (formic acid) and 27 kJ/g (sorbic acid). Pearlin et al. (2019) calculated that 1 M of fumaric acid generates 1.340 kJ or 18 M ATP; this is comparable to the energy provision of glucose. Citric acid’s energy provision is similar; acetic and propionic acid require 18 and 15 % more energy to generate 1 M ATP.

Acidifiers improve immune response

The immune system, especially at the sensitive life stage of weaning, plays an essential role for the piglet. Acidifiers have been shown to stimulate or support the immune system. Ahmed et al. (2014) showed that citric acid (0.5 %) and a blend of acidifiers composed of formic, propionic, lactic, phosphoric acid + SO2(0.4 %) significantly increased the level of serum IgG. IgG are part of the humoral immune system. They mark foreign substances to be eliminated by other defense systems.


In a trial conducted by Ren et al. (2019), piglets receiving a mixture of formic and propionic acid showed lower concentrations of plasma tumor necrosis factor-α, regulating the activity of diverse immune cells. Furthermore, interferon-γ and interleukin (Il)-1ß were lower than in the control group after the challenge with E. coli (ETEC). In this trial, the addition of organic acids to the feed alleviated the inflammatory response in a way comparable to antibiotics.

In a nutshell

Organic acids are no longer seen as pure acidifiers but as growth promoters and potential antibiotic substitutes due to their positive effect on the gastrointestinal tract. Their main effect, the decrease of pH, entails consequences from inhibiting pathogenic bacteria and improved digestion to enhanced health and growth.
Research indicates that acidifiers can be a viable alternative to antibiotic growth promoters and ZnO for ensuring healthy piglet production after weaning.




Piglet performance with fewer antimicrobials is possible

veterinarianholdingdryfoodingranulesinhandsandoffering

By Technical Team, EW Nutrition

A variety of stressors simultaneously occur at weaning, making this probably the most challenging period in pig production. During weaning, we commonly see altered gut development and gut microbiome, which increases piglets’ vulnerability to diseases. The most classic clinical symptom resulting from these stressors is the occurrence of post-weaning diarrhea. It is a sign that something went wrong, and piglet development and overall performance may be compromised (Guevarra et al. 2019).

Besides weaning, an unavoidable practice in pig production, the swine industry has been facing other changes. Among them, the increased pressure to reduce the use of antimicrobials stands out. Antimicrobials are often associated with improved piglet performance and health. Their usage has been reduced worldwide, however, due to the threat of antimicrobial resistance that affects not just animal health but also human health (Cardinal et al., 2019).

Reduce antimicrobials and post-weaning diarrhea: can piglet nutrition achieve both?

With these drastic changes for the piglets and the global swine industry, producers must find solutions to keep their farms profitable — especially from a nutritional perspective. Our last article presented two feed additives that can be part of an antibiotic-free concept for post-weaning piglets. This article will highlight a few essential nutritional strategies that swine producers and nutritionists must consider when formulating post-weaning feed without or with reduced amounts of antimicrobials.

Pigs

What makes weaning so stressful for piglets?

Producers, nutritionists, and veterinarians all agree that weaning is a tough time for piglets (Yu et al., 2019) and, therefore, a challenge to all those involved in the pig production chain. Although there is a global trend towards increasing weaning age, generally speaking, animals are still immature when going through the weaning process. They face several physiological, nutritional, and environmental changes (figure 1).

Healthy Piglets
Figure 1. Factors associated with weaning can compromise piglet well-being and performance

Most of these changes become “stressors” that trigger a cascade of reactions affecting the balance and morphology of the intestinal microbiome (figure 2). The outcome is a decrease in the piglets’ well-being and, in most cases, performance. We need to clearly understand how these stressors affect pigs to develop effective strategies against post-weaning growth impairments, especially when no antimicrobials are allowed.

 

Schematic diagram
Figure 2. Schematic diagram illustrating the effects of stress in weaned piglets (adapted from Jayaraman and Nyachoti, 2017)

Weaning support starts before weaning

The use of creep feed has been evaluated and even criticized for many years. Some operations are still reluctant to use such a feed due to its high cost and amount of labor on the farm, with manually providing feed and cleaning feeding trays. In addition, some questions have been raised regarding the ideal composition of the creep feed – how much complexity should we add to this special diet?

Therefore, the benefits of creep feed are under re-evaluation, not only considering piglet physiology per se, but also feed characteristics and different feeding programs. Recent studies have questioned highly complex creep feed formulations. Creep feed is being called “transition feed” (Molist, 2021) – i.e., that meal which is complementary to sows’ milk and not a replicate of it, helping piglets during the period of changing its main source of nutrients. We must, therefore, look at it as a way of making piglets familiar with solid feed, as highlighted by Mike Tokach during the 2020 KSU Swine Day. Dr. Tokach also mentioned that the presence of feeders in the lactation pen could stimulate the exploratory behaviors of the piglets. Combined, these practices can lead to a higher feed intake and performance during the nursery phase.

Towards a pragmatic stance on creep feed

Heo et al. (2018) evaluated three different creep feed types: a highly digestible creep feed, weaning feed as creep feed, and sow feed as creep feed until weaning. Piglets receiving the highly digestible creep had higher feed intake during the second to the last week pre-weaning (14 to 21 days of age) and higher ADG during the last week pre-weaning (21 to 28 days of age). This resulted in a trend for higher weaning weight. However, these benefits did not persist after weaning when all piglets received the weaning feed.

Guevarra et al. (2019) also suggested that the abrupt transition in piglet nutrition to a more complex nutrient source can influence shifts in the gut microbiota, impacting the absorptive capacity of the small intestine. Yang et al. (2016) evaluated 40 piglets from eight litters during the first week after weaning. They found that the change in diet during weaning reduced the proliferation of intestinal epithelial cells. This indicates that this period affects cellular macromolecule organization and localization, in addition to energy and protein metabolism. These results suggest that “similarity” in feed pre- and post-weaning may contribute more to the continuity of nutrient intake post-weaning than a highly complex-nutrient dense creep feed.

Nutritional strategies without antibiotics: focus on pig physiology

As mentioned, it is crucial to avoid a drastic drop in feed/nutrient intake after weaning compared to pre-weaning levels. In a classic study, Pluske et al. (1996) showed the importance of high intake levels on villus weight (used as a reference for gut health, cf. graph 1). Although not desirable, the reduction should be considered “normal” behavior.

Imagine these recently weaned piglets, facing all these stressors, having to figure out within this new group of peers when it is time to eat, where to find food, why water and food now come from two distinct sources… Therefore, management, feeding, water quality, and other aspects play important roles in post-weaning feed intake (figure 3).

Average villus height
Graph 1. Villus height following different levels of feed intake (M = maintenance) post-weaning (a.b.c bars with unlike superscript letters are different at P<0.05). (From Pluske et al., 1996.)

From a nutritional perspective, piglets at weaning experience a transition from milk (a high-fat, low-carbohydrate liquid) to a plant-based diet (a solid, low-fat, and high-carbohydrate diet) (Guevarra et al., 2019). Even when previously introduced to solid feed, it is still difficult for their enzymatic system to cope with grains and beans.

One of the consequences of the lower digestibility capacity is an increase of undigested nutrients. Harmful bacteria thrive and cause diarrhea, reducing even further an already compromised feed intake. This cycle must be broken with the support of formulations based on piglet physiology.

Post-weaning feed must support digestion and nutrient absorption, including the largest possible share possible of high-quality, digestible ingredients, with low anti-nutritional factors. High-performing feed also integrates functional amino acids, functional carbohydrates, and additives to support the intestinal mucosa and gut microbiome.

Supporting piglets with effective solutions

Figure 3. Supporting piglets with effective solutions

Crude protein – more of the same?

Levels of crude protein in piglet feed have been in the spotlight for quite some time. The topic can be very controversial where the exact percentage of crude protein in the final feed is concerned. Some nutritionists pragmatically recommend maximal levels of 20% in the weaner feed. Others go a bit lower, with some formulations reaching 17 to 18% total crude protein. Levels above 20% will incur high costs and may accentuate the growth of pathogenic bacteria due to a higher amount of undigested protein in the distal part of the small intestine (figure 4).

crude protein levels in piglet feed
Figure 4. The dynamics of crude protein levels in piglet feed

What is not open for discussion, however, is the quality of the protein used, in terms of:

  • digestibility,
  • the total amount of anti-nutritional factors, and
  • the correct supply of essential and non-essential amino acids (particularly lysine, methionine, threonine, tryptophane, isoleucine and valine).

The critical role of digestibility

High-digestibility ingredients for piglets need to deliver minimum 85% digestibility. In most cases, to reach high biological values (correlating to high digestibility), these ingredients typically undergo different processing steps, including heat, physical, and chemical treatments. Animal by-products (such as hydrolyzed mucosa, fish meal, spray-dried plasma) and processed vegetable sources (soy protein concentrate, extruded grains, potato protein) can be used in high amounts during this phase. They will notably reduce the total amount of undigested protein reaching the distal part of the intestine, with 2 main benefits:

  • Less substrate for pathogenic bacteria proliferation (and therefore lower incidence of diarrhea)
  • Lower nitrogen excretion to the environment

 

Animal Feeds

It is common knowledge that certain storage proteins from soybean meal (for instance, glycinin and B-conglycinin) can cause damage to piglets’ intestinal morphology and trigger the activation of the immune system. However, it is normal practice to introduce this ingredient to piglets around weaning so that the animals can develop a certain level of tolerance to such compounds (Tokach et al., 2003). In Europe, where most diets are wheat-barley based, soybean meal is included in levels varying from 3 to 9% in the first 2 diets, with gradual increases during the nursery phase.

Amino acids and protein: manage the balance

When the supply and balance between essential and non-essential amino acids is concerned, reducing total crude protein brings indeed complexity to the formulations. The concept of ideal amino acid should be expanded, ideally, to all 9 essential amino acids (lysine, methionine, tryptophan, threonine, valine, isoleucine, leucine, histidine, and phenylalanine). In most cases, formulations go up to the 5th or 6th limiting amino acid. Lawor et al. (2020) suggest 2 practical approaches to avoid deficiencies when formulating low-protein piglet feed:

  • Maintain a maximum total lysine to crude protein ratio in the diet of 7.1 to 7.4%
  • Do not exceed the SID lysine to crude protein ratio of 6.4%

Some conditionally essential amino acids (e.g. arginine, proline, and glutamine) also play critical roles in diets with reduced crude protein levels. Glutamine is especially interesting. When supplemented in the feed, it can be used as a source of energy by the intestinal epithelium and, therefore, prevent atrophy and support nutrient absorption, resulting in better growth post-weaning (Hanczakowska and Niwińska, 2013; Watford et al., 2015)

The importance of the buffer capacity of the feed – supporting the enzymatic system

Given the move towards antibiotic reduction, this topic is more relevant than ever to nutritionists worldwide. The acid-binding capacity (also known as buffering capacity) of the feed directly affects the capacity of the stomach to digest protein. Hence, buffer capacity is of utmost importance in antimicrobial-free diets as it influences the growth of pathogenic bacteria (Lawlor et al., 2005).

In short, the acid-binding capacity is the resistance of an ingredient or complete feed to pH change. For piglet feed/feed ingredients, it is normally measured by the acid-binding capacity at pH4 (ABC-4). A higher ABC-4 equates to a higher buffering capacity. Feed with a high ABC-4 would require large amounts of gastric acid for the pH of the stomach to reach 4 and below. As the post-weaned piglet has limitations on producing and secreting acid, the stomach pH would stay high and, thus, less favorable for protein digestion.

The recommendation is to have a complete feed based on single ingredients with low ABC-4 values and to use additives that further reduce the ABC-4 value (such as organic acids). According to Molist (2020), post-weaning feed must have an ABC-4 that is lower than 250-300 meq/kg.

Talking about fiber

Dietary fibers are also known for regulating intestinal health in both humans and animals. Chen et al. (2020), for example, examined the effects of dietary soluble fibers (inulin) and insoluble fibers (lignocellulose) in weaned piglet diets for four weeks. Results showed that combining those fibers can positively influence nutrient digestibility, gut microbiota composition, intestinal barrier functions, and growth performance (table 1 ).

Effects of dietary fiber supplementation on piglet growth performance
Table 1. Effects of dietary fiber supplementation on piglet growth performance (adapted from Chen et al., 2020)

How to reduce antimicrobials? Understand the roles of piglet physiology and nutrition

Swine producers might think that “How can I reduce antimicrobial use on my farm?” and “How can I improve the performance of piglets at weaning?” are two separate questions. However, that is not always the case. Answers based on a deep understanding of physiology and nutrition dynamics help piglets overcome the challenges encountered during weaning – and, thus, lessen the need for antimicrobial interventions.

In this article, we have explored the basic principles that are the basis for ensuring the performance and health of the post-weaning piglet. Although we do not have a singular solution for eliminating antimicrobials on our pig farms, we can count on a group of robust and integrated nutritional strategies. By integrating factors ranging from management to feed additives, these solutions can improve piglet health and performance throughout their lives.

 

To know more about Gut health products click here.




INFOGRAPHIC: Healthy piglets after weaning

swine piglet kv

Piglet weaning is a critical period. When not properly managed, it leads to decreased performance, diarrhea, and sometimes mortality. 

The six areas of intervention in our infographic will help pig producers manage these stressors, avoid diarrhea, and maintain piglet health and performance. 

 

Piglets health and performance

 

 




INFOGRAPHIC: Why large litters could mean higher mortality

swine sow piglet kv

The benefits imprinted by genetics with more piglets/sows can be lost along the way to weaning. What can decrease performance and increase mortality in such cases? Why do higher litter sizes so often correlate with higher mortality?

Why large litters could mean higher mortality

 




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.

 

 




Egg immunoglobulins as a plasma replacer

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Animal plasma has been widely used in piglet feeding, not only as a protein source, but also as a tool to reduce gastrointestinal disorders after weaning.
Drs FELLIPE BARBOSA and INGE HEINZL* consider a safe alternative in order to keep animals healthy and to avoid loss of performance.

The recent developments surrounding the health risks associated with using animal plasma as a piglet feed ingredient is growing serious concerns in China. After the reported cases of African swine fever (ASF) commencing in August 2018, the Chinese government decided to ban the use of pig blood (and its by-products) in animal feed for some time.

The reason for the temporary ban of pig blood ingredients: African swine fever.
ASF is a viral disease of pigs and wild boars. The virus causes a lethal hemorrhagic disease in pigs. In some cases, the death of infected animals can occur during one week after the infection. There are no vaccines against the ASF Virus. When it hits the herd it is virtually impossible to stop its spread contaminating all animals.
Spreading of the virus occurs as follows:
• contact with contagious pigs from infected areas,
• contact with contaminated materials, being fed with kitchen waste and
• non-trusted animal origin feed ingredients.

There is a risk of pig blood carrying different types of viruses like ASF virus. Therefore, from time to time the use of ingredients based on blood is questioned by pig producers. To minimise this risk, the use of ingredients derived from pig slaughterhouses (including animal plasma) in pig feed is no longer allowed in China. This measure will cause not only a protein deficit in piglet feeds but also reduced protection of weaned piglets when intestinal disorders are concerned.

Immunoglobulins from animal plasma and its benefits on reducing post-weaning diarrhea (PWD)
The use of animal plasma has a positive effect on post-weaning performance of piglets. It is generally known that as a palatable ingredient, animal plasma stimulates feed intake. This results in better growth and a higher post-weaning performance in piglets. However, a closer inspection on the mode of action of spray dried plasma reveals its properties as an immune-ingredient and shows its supporting effect on the overall health status of the animals. Scientific publications showed that the positive influence on growth when feeding plasma to piglets is mainly due to its “immunoglobulin fraction”. This assigns to plasma a specific role in nutrition of weaned pigs to prevent PWD and to reduce the need for antibiotics.

Egg immunoglobulins: a natural way of protecting weaned piglets
Globigen® Jump Start (EW Nutrition GmbH) is a functional and standardized product based on whole egg powder. It contains natural immunoglobulins (IgY – “immunoglobulins from yolk”) mixed with a carrier. IgY are cells of the immune system from birds similar to the IgG in mammals. They have the main function of identifying and neutralizing harmful substances in the body. IgYs are obtained through a non-invasive process and are natural ingredients from eggs. There is no connection with blood and slaughter by-products and therefore no risk of carrying animal diseases.
Globigen® Jump Start is used to support piglets during critical stages of life, as long as their natural immunity is not completely developed. Scientific data confirmed that the IgY present in egg powder are capable of supporting intestinal health and growth performance of newly weaned piglets. More recently, also the possibility of using immunoglobulins as alternatives to zinc oxide (ZnO) and in-feed antibiotics (Hedegaard et al., 2017; Li at al. 2015) were evaluated with promising results.

Better results than plasma IgG: understanding the antigens causing post-weaning diarrhea
Animal plasma is a by-product of the meat industry. The animals slaughtered were possibly exposed to various diseases over their whole life. It cannot be considered as a standardized product in terms of immunoglobulins (either quantity nor quality). The Ig contained could be useful but also totally useless, depending on the pathogens the animals have been confronted with. As a source of immunoglobulins Globigen Jump Start is a costefficient and effective alternative to replace plasma in piglets’ diets. Its IgY content will have the same protection effect in the gut as IgG, but the nutritionist will have the possibility of choosing different protein sources in the market, either because of price or availability of raw materials. Our recommendation is that 40kg of plasma can be replaced by 2kg of Globigen Jump Start supplied with different high digestible protein sources.

A piglet trial was conducted with the objective of evaluate the efficacy of egg immunoglobulins on performance parameters of weaned piglets and to evaluate it as a substitute for animal plasma. Piglets were challenged with F4 and F18 entertoxic E. coli (ETEC) strains and feed either 2kg of Globigen Jump Start (GJS) or 40kg of spray dried plasma (SDP) in the weaner diet. The comparison was also done to a negative group (NG – microbiological challenge and no protection in the diet); and a positive group (PG – no microbiological challenge and antibiotics + ZnO in the diet).

Piglets from NG had lower feed intake, weight gain, and feed efficiency than animals from PG. The same was observed for piglets from GJS and SDP group. However, the impact of bacterial challenge on weight gain was lower for GJS piglets than for SDP (-14% and -52% when compared to PG); whereas feed intake was similar for both groups (-13% and -14% when compared to PG). The results showed that piglets receiving GJS where more efficient on converting feed into growth even when challenged when compared to SDP animals.

Trial conclusion
In this trial, the product based on egg immunoglobulins showed better influence on the performance of piglets than blood plasma. This may be due to the fact that the quality of the plasma depends on the animals slaughtered and on their contact with diseases, determining how much and which antibodies are available in this feed.
Additionally, blood plasma includes the danger of infectious diseases.

Safe and standard: free of swine related diseases and ruminant material
EW Nutrition clearly understands the importance of maintaining standardisation. It is a key factor for the customers to have a product that they can depend on every day.
Therefore, trough specific steps during the production of Globigen products, EW Nutrition ensures product quality. During production, all eggs are pasteurised and dried to a whole egg powder. In between steps include microbiological analysis, Salmonella, and avian disease controls to ensure the final product is free of the mentioned threats. Furthermore, as Globigen products are originated from laying hen farms there is no risk of contamination with any swine disease, like the devastating ASF. Finally, Globigen products do not contain any raw materials produced from, or substances derived from ruminants nor do the products come in contact with risk materials during the whole process (not be at risk for carrying transmissible spongiform encephalopathy or bovine spongiform encephalopathy – BSE).

 

ASIAN FEED MAGAZINE – February/March 2019




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 Inge Heinzl.
Published on PigProgress | 20th July, 2018.

 




Using egg immunoglobulins to enhance piglet survival

sow management

The number of healthy piglets weaned is the most important factor for the calculation of profit in piglet production.

Losses in the farrowing unit normally occur during the first seven days of life as piglets are born with very little protection in the form of immunity. The intake of immunoglobulins from colostrum is therefore of vital importance. Besides cleanliness and special feeding, piglets can be additionally supported by two strategies that mimick the effect of colostrum:
– a direct one, meaning the feeding of immunoglobulins (IgY from eggs) to piglets that would support the immune system in the gut or
– an indirect one, meaning a supply of IgY to the sow to keep the pathogenic pressure in the farrowing unit as low as possible.

Piglets are born with no immune protection and very low energy reserves
It is well known that piglets are physiologically immature at birth. Their energy reserves are very low with only 1 – 2% body fat comprising mainly of structural and subcutaneous fat. Therefore, in the first hours of life they rely on the glucose supply from glycogen from the liver as their main energy source. However, this will only cover their needs for a few hours.
Due to the construction of the sow’s placenta, a transfer of immunoglobulins (antibodies) within the uterus is not possible. This means that piglets are born with practically no immune protection and depend on the immediate intake of immunoglobulins from colostrum. The immunoglobulins can be absorbed in the gastrointestinal tract and immediately transferred into the bloodstream – but also only for a short time. The absorption ability of the piglets starts to decrease soon after birth and ends after 24 to 36 hours.

Strategy 1: Making the farrowing unit as safe as possible
The piglets’ environment should be warm to prevent hypoglycaemia. Piglets looking for heat close to the sow can also get crushed. Since the temperature needs of the sow and piglets are different, a piglet nest with a special heat lamp is recommended. Furthermore, the farrowing unit should be clean. Due to their low immune status, piglets are susceptible to common pathogens such as E. coli, Clostridium perfringens, and rotavirus that can all lead to diarrhoea.

Most pathogens can be traced to those found in the sow’s faeces. To keep this amount as low as possible, different measures can be taken:
– A vaccination increases the immune defences of the sow. The antibodies fight against the pathogens so that less “functioning” pathogens are excreted.
– Feeding of probiotics increases the number of good bacteria like Lactobacilli and Bifidobacteria competing with the pathogens for binding sites and nutrients.
– Administration of egg immunoglobulins, which bind to the pathogens within the gastrointestinal tract and make them harmless. These pathogen-immunoglobulin-complexes can be ingested by the piglets without any danger.

Strategy 2: Supporting the piglets with immunoglobulins
The aim here is to strengthen the local immunity in the gastrointestinal tract by increasing the amount of immunoglobulins (Ig). As already mentioned, the intake of sow colostrum is of vital importance. With the vaccination of the sow, the content of antibodies in the colostrum can even be enhanced.
An additional measure would be to orally supply the piglets with egg immunoglobulins (IgY). Both classes of immunoglobulins (IgG from mammals, and IgY from birds) can bind to pathogens in the gut, preventing them from binding to the intestinal wall and reducing the incidence of diarrhoea. The difference is in the degree of effectiveness and specificity.

Conclusion
To maximize the number of piglets weaned, it is necessary to support their immune system during the first days of life. Besides good hygiene management, the administration of egg antibodies to the sow will also help reduce the amount of shed pathogens keeping the pathogenic pressure low. The application of egg antibodies directly to the piglets supports their immune system by binding the pathogens in the gut, minimizing the risk of diarrhoea.