By Dr. Ajay Awati, Global Director Enzymes, EW Nutrition

In recent years, the scientific understanding of xylanase inhibitors (XIs) and their impact on animal nutrition has grown significantly. Xylanase, a crucial enzyme used to enhance nutrient availability in feed, can face challenges from XIs present in cereal grains. This article explores the evolution of plant protection mechanisms, the economic impact of XIs, and the development of a novel xylanase, Axxess XY, resistant to these inhibitors.

Xylanase inhibitors – an evolutionary protection mechanism of plants

Xylanase inhibitors (XI) are a classic example of the evolutionary development of protection mechanisms by cereal plants against pathogens. Microorganisms, such as fungal pathogens, involve the degradation of xylan as one of the mechanisms in pathogenesis (Choquer et al., 2007). There are also other mechanisms by which microorganism-produced xylanases affect plants.

To protect themselves, plants evolved xylanase inhibitors to prevent the activities of xylanases. XIs are plant cell wall proteins broadly distributed in monocots. There are three classes of XIs with different structures and inhibition specificities (Tundo et al., 2022):
1. Triticum aestivum xylanase inhibitors (TAXI)
2. Xylanase inhibitor proteins (XIP), and
3. Thaumatin-like xylanase inhibitors (TLXI).

Xylanase inhibitors have an economic impact

In animal nutrition, xylanases are widely used in diets containing cereal grains and other plant materials to achieve a higher availability of nutrients. The inhibitory activity of XIs prevents this positive effect of the enzymes and, therefore, makes them economically relevant. Studies have reported that higher levels of XIs negatively impact broiler performance. For example, in one of the studies, broilers fed with grains of a cultivar with high inhibitory activity showed a 7% lower weight on day 14 than broilers fed with grains of a cultivar with less inhibitory activity (Madesen et al., 2018). Another study by Ponte et al. (2004) also concluded that durum wheat xylanase inhibitors reduced the activity of exogenous xylanase added to the broiler diets.

Xylanase inhibitors can withstand high temperatures

Even though XIs can impact the performance of exogenous xylanase in different ways, only minor attention was paid to the reduction of xylanase’s susceptibility to xylanase inhibitors during the xylanase development in the last decades. Firstly, the issue was ignored mainly through the assumption that XIs are denatured or destroyed during pelleting processes. However, Smeets et al. (2014) showed that XIs could sustain significant temperature challenges. They demonstrated that after exposing wheat to pelleting temperatures of 80°C, 85°C, 92°C, and 95°C, the recovery of inhibitory activity was still 99%, 100%, 75%, and 54%, respectively. Furthermore, other studies also confirmed that conditioning feed at 70-90°C for 30 sec followed by pelleting had little effect on the XI activity in the tested feed, showing that xylanase inhibitors are very likely present in most xylanase-supplemented feeds fed to animals.

Do we only have the problem of xylanase inhibitors in wheat?

No. After first reports of the presence of xylanase inhibitors in wheat by Debyser et al. (1997, 1999), XIs were also found in other cereal grains (corn, rice, and sorghum, etc.), and their involvement in xylanase inhibition and plant defense has been established by several reports (Tundo et al., 2022).

In most of the countries outside Europe, exogenous xylanase is used not only in wheat but also in corn-based diets. Besides broiler feeds, also other animal feeds, such as layer or swine feed being part of more mixed-grain diets, are susceptible to the inhibitory activity of XIs. Nowadays, the situation is getting worse with all the raw material prices increasing and nutritionists tending to use other feed ingredients and locally produced cereals. They need a xylanase which is resistant to xylanase inhibitors.

Xylanases’ resistance to XIs is crucial – Axxess XY shows it

To prevent xylanases from losing their effect due to the presence of xylanase inhibitors, the resistance of new-generation xylanases to these substances is paramount in the development process, including enzyme discovery and engineering.

In the past 25 years, scientists have learned much about XI-encoding genes and discovered how xylanase inhibitors can block microbial xylanases. Additionally, there has been a significant increase in understanding the structural aspects of the interaction between xylanases and XIs, mainly how xylanase inhibitors interact with specific xylanases from fungi or bacteria and those in the GH10 or GH11 family. With such understanding, a new generation xylanase, Axxess XY, was developed. Besides showing the essential characteristics of intrinsic thermostability and versatile activity on both soluble and insoluble arabinoxylan, it is resistant to xylanase inhibitors.

Axxess XY takes xylanase application in animal feeds to the next level.

Axxess XY outperforms other xylanases on the market

Recent scientific developments (Fierens, 2007; Flatman et al., 2002; Debyser, 1999; Tundo et al., 2022; Chmelova, 2019) and internal research can be summarized as follows:

Figure 1: Schematic summary of the susceptibility of different xylanase to xylanase inhibitors from three main groups.

The high resistance to xylanase inhibitors is one of the reasons that a novel xylanase with bacterial origin and from the GH-10 family was chosen to be Axxess XY. EWN innovation, together with research partners, made an interesting benchmark comparison between xylanases that are commercially sold by different global suppliers and Axxess XY. For these trials, all xylanase inhibitors from wheat were extracted. The inhibitors, together with the respective xylanase, were incubated at 40⁰C (to mimic birds’ body temperature) for 30 mins. Then, the loss of xylanase activity was calculated by analyzing remaining activity after incubation. Results are shown below in Figure 2. There were varying levels of activity loss observed in the different commercially sold xylanases. In some xylanases, the losses were alarmingly high. However, Axxess XY was not inhibited at all.

Fig. 2: Extracted total xylanase inhibitors from wheat incubated with the respective xylanase at 40°C for 30 mins. – Loss of activity after incubation with xylanase inhibitors

Conclusion:

Xylanase inhibitors are present in all cereal grains and, unfortunately, heat tolerant (up to 90⁰C, still 75% of inhibition activity was retained). Regardless of the diets used, there is a possibility that the xylanase used may come across xylanase inhibitors, resulting in a loss of activity. More importantly, this can lead to inconsistent performance.

For effective, consistent, and higher performance of NSP enzyme application, it is a must to use xylanase that is resistant to xylanase inhibitors.

Literature:

Chmelová, Daniela, Dominika Škulcová, and Miroslav Ondrejovic. “Microbial Xylanases and Their Inhibition by Specific Proteins in Cereals.” KVASNY PRUMYSL 65, no. 4 (2019). https://doi.org/10.18832/kp2019.65.127. LINK

Choquer, Mathias, Elisabeth Fournier, Caroline Kunz, Caroline Levis, Jean-Marc Pradier, Adeline Simon, and Muriel Viaud. “Botrytis CinereaVirulence Factors: New Insights into a Necrotrophic and Polyphageous Pathogen.” FEMS Microbiology Letters 277, no. 1 (2007): 1–10. https://doi.org/10.1111/j.1574-6968.2007.00930.x. LINK

Debyser, W, WJ Peumans, EJM Van Damme, and JA Delcour. “Triticum Aestivum Xylanase Inhibitor (Taxi), a New Class of Enzyme Inhibitor Affecting Breadmaking Performance.” Journal of Cereal Science 30, no. 1 (1999): 39–43. https://doi.org/10.1006/jcrs.1999.0272. LINK

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.

Figure 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

Total Production 2023: 144.3 million metric tons for farmed animals

Change from 2022: 2% decrease

Factors Influencing Decrease

Political and Market Pressures: Addressing crises and the shift towards sustainable feed.

Climate and Diseases: Effects of droughts, floods, Avian Influenza (AI), and African Swine Fever (ASF) on raw material supply and animal production.

National Policies: Initiatives for greenhouse gas and nitrate emission reduction.

Consumer Trends: Food price inflation impacting demand.

Production Variability: Different trends across EU Member States, with notable decreases in countries like Germany, Ireland, Denmark, and Hungary, and slight increases in Austria, Bulgaria, Italy, and Romania.

Sector-Specific Trends

Pig Feed: Major decline of nearly 2.5 million tons. Key challenges included:

• Loss of export markets, particularly in Asia
• Negative media impact in Germany
• Significant production drop in Denmark (-13.6%) and Spain (loss of 800,000 metric tons)
• Italy’s ongoing struggle with ASF

Poultry Feed: Increase by 0.9 million tons, yet still 700,000 metric tons below 2021 levels. Challenges included declines in Hungary and Czechia due to reduced broiler production.

Cattle Feed: Decrease of 0.8 million tons from 2022.

2024 key factors

• Animal disease
• Economic instability, persistent food price inflation
• Weather irregularities
• Continued imports of poultry meat from Ukraine
• “Green and animal welfare” policies affecting local production

Summary

The EU’s compound feed production in 2023 faced numerous challenges, leading to an overall decrease. The pig feed sector was most severely hit, while poultry feed showed some recovery. The influence of environmental, economic, and policy factors played a significant role in shaping these trends. Despite the price of feed cereals falling back to the levels seen before Russia’s invasion of Ukraine, these challenges will continue to be felt in 2024.

Source: FEFAC

Dr Inge Heinzl, EW Nutrition

Endotoxins are… toxic, of course. The part “endo” in their name means that they are part of the bacterial cell, or, to specify it, they are part of the outer membrane of Gram-negative bacteria such as E. coli, Salmonella, Shigella, Klebsiella, and Pseudomonas.

When do they occur?

Always. Endotoxins are released with the lysis of bacteria, e.g., at the end of their life cycle, due to the effective immune defense of the host or treatments. The other possibility is bacterial growth as the membrane gets restructured and the endotoxins (or lipopolysaccharides -LPS-) are liberated.

What is the problem?

The “normal” occurrence (animals and humans always have Gram-negative bacteria in their gut) does not matter, because gut cells do not have receptors to recognize them as a danger in their apical side. However, when the barrier function is compromised, they pass into the bloodstream.

The liver still detoxifies small amounts. The problem comes with higher amounts of endotoxins in the bloodstream. Then, they provoke a strong immune reaction, feed intake drops, and nutritional resources are shifted from growth and production to immunity. These performance drops affect the profitability of the farmer.

What can be done?

Use broad-spectrum toxin binders that

• • contain clay minerals showing high affinity and selectivity against endotoxins
  • contain yeast cell walls, which, in addition to their binding capacity, support the immune response through macrophage activation and are involved in modulating microflora and bacterial load from the intestine
  • provide adequate liver protection.

By Dr. Inge Heinzl, Editor, EW Nutrition

Salmonellosis is third among foodborne diseases leading to death (Ferrari, 2019). More than 91,000 human cases of Salmonellosis are reported by the EU each year, generating overall costs of up to €3 billion a year (EFSA, 2023), 10-20% of which are attributed to pork consumption (Soumet, 2022). The annual costs arising from the resulting human health losses in 2010 were about €90 million (FCC Consortium, 2010). Take the example of Ireland, where a high prevalence of Salmonella in lymph nodes still shows a severe issue pre-slaughter and a big challenge for slaughterhouses to stick to the process hygiene requirements (Deane, 2022).

Several governments already have monitoring programs in place, and the farms are categorized according to the salmonella contamination of their pigs. In some countries, e.g., Denmark, an economic penalty of 2% of the carcass value must be paid if the farm has level 2 (intermediate seroprevalence) and 4-8% if the level is 3. Other countries, e.g., Germany, the UK, Ireland, or the Netherlands, use quality assurance schemes. The farmers can only sell their carcasses under this label if their farm has a certain level.

Let’s take a quick look at the genus of Salmonella

Salmonellas are rod-shaped gram-negative bacteria of the family of enterobacteria that use flagella for their movement. They were named after the American vet Daniel Elmer Salmon. The genus of Salmonella consists of two species (S. bongori and S. enterica with seven subspecies) with in total more than 2500 serovars (see Figure 1). The effects of the different serovars can range from asymptomatic carriage to severe invasive systemic disease (Gal-Mor, 2014). All Salmonella serovars generally can cause disease in humans; the rosa-marked ones already showed infections.

Figure 1: the genus of Salmonella with Salmonella serovars relevant for pigs (according to Bonardi, 2017: Salmonella in the pork production chain and its impact on human health in the European Union)

Within the group of Salmonella, some serovars can only reside in one or few species, e.g., S. enterica spp. enterica Serovar Dublin (S. Dublin) in bovines (Waldron, 2018) or S. Cholerasuis in pigs (Chiu, 2004). An infection in humans with these pathogens is often invasive and life-threatening (WHO, 2018). On the contrary, serovars like S. Typhimurium and S. Enteritidis are not host-specific and can cause disease in various species.

The serotypes S. Typhi and S. Paratyphi A, B, or C are highly adapted to humans and only for them pathogenic; they are responsible for the occurrence of typhus.

Serovars occurring in pigs and relevant for humans are, for example, S. Typhimurium (Hendriksen, 2004), S. Serotype 4,[5],12:I (Hauser et al., 2010), S. Cholerasuis (Chiu, 2004), S. Derby (Gonzalez-Santamarina, 2021), S. Agona (Brenner Michael, 2006) and S. Rissen (Elbediwi, 2021).

Transmission of Salmonella mostly happens via contaminated food

The way of transmission to humans depends on the serovar:
Human-specific and, therefore, only in humans and higher primates residing serovars S. Typhi and Paratyphi A, B, or C (typhoidal) are excreted via feces or urine. Therefore, any food or water contaminated with the feces or urine of infected people can transmit this disease (Government of South Australia, 2023). Typhoid and paratyphoid Salmonellosis occur endemic in developing countries with the lack of clean water and, therefore, inadequate hygiene (Gal-Mor, 2014).

Serovars which can cause disease in humans and animals (non-typhoidal), can be transmitted by
– animal products such as milk, eggs, meat
– contact with infected persons/animals (pigs, cows, pets, reptiles…) or
– other feces- or urine-contaminated products such as sprouts, vegetables, fruits….

Farm animals take salmonellas from their fellows, contaminated feed or water, rodents, or pests.

Symptoms of Salmonellosis can be severe

In the case of typhoid or paratyphoid Salmonellosis, the onset of illness is gradual. People can suffer from sustained high fever, unwellness, severe headache, and decreased appetite, but also from an enlarged spleen irritating the abdomen and dry cough.

A study conducted in Thailand with children suffering from enteric fever caused by the typhoid serovars S. Typhi and Paratyphi showed a sudden onset of fever and gastrointestinal issues (diarrhea), rose spots, bronchitis, and pneumonia (Thisyakorn et al., 1987)

The non-typhoid Salmonellosis is typically characterized by an acute onset of fever, nausea, abdominal pain with diarrhea, and sometimes vomiting (WHO, 2018). However, 5% of the persons – children with underlying conditions, e.g., babies, or people who have AIDS, malignancies, inflammatory bowel disease, gastrointestinal illness caused by non-typhoid serovars, and hemolytic anemia, or receiving an immunosuppressive therapy can be susceptible to bacteremia. Additionally, serovars like S. Cholerasuis or S. Dublin are apt to develop bacteremia by entering the bloodstream with little or no involvement of the gut (Chiu, 1999). In these cases, consequences can be septic arthritis, pneumonia, peritonitis, cutaneous abscess, mycotic aneurysm, and sometimes death (Chen et al., 2007; Chiu, 2004, Wang et al., 1996).

In pigs, S. Cholerasuis causes high fever, purple discolorations of the skin, and thereinafter diarrhea. The mortality rate in pigs suffering from this type of Salmonellosis is high. Barrows orally challenged with S. Typhimurium showed elevated rectal temperature by 12h, remaining elevated until the end of the study. Feed intake decreased with a peak at 48h after the challenge and remained up to 120h after the challenge. Daily gain reduced during the following two weeks after infection. A higher plasma cortisol level and a lower IGF-I level could also be noticed. All these effects indicate significant changes in the endocrine stress and the somatotropic axis, also without significant alterations in the systemic pro-inflammatory mediators (Balaji et al., 2000)

To protect humans, Salmonella in pork must be restraint

There are three main steps to keep the contamination of pork as low as possible:

1. Keeping Salmonella out of the pig farm
2. Minimizing spreading if Salmonella is already on the farm
3. Minimizing contamination in the slaughterhouse

1. How to keep Salmonella out of the pig farm?

To answer this question, we must look at how the pathogen can be transported to the farm. According to the Code of Practice for the Prevention and Control of Salmonella on Pig Farms (Ministry of Agriculture, Fisheries and Food and the Scottish Executive Rural Affairs Department), there are several possibilities to infiltrate the pathogen into the farm:

• Diseased pigs or pigs which are ill but don’t show any symptoms
• Feeding stuff or bedding contaminated with dung
• Pets, rodents, wild birds, or animals
• Farm personnel or visitors
• Equipment or vehicles

Caution with purchased animals!

To minimize/prevent the entry of Salmonella into the livestock, bought-in animals must come from reputable breeding farms with a salmonella monitoring system in place. As possible carrier animals are more likely to excrete Salmonella when stressed; they should be kept in isolation after purchasing. Additionally, the animals must go through a disinfectant foot bath before entering the farm.

Keep rodents, wild animals, and vermin in check!

Generally, the production site must be kept clean and as unattractive as possible for all these animals. Rests of feed must be removed, and dead animals and afterbirths must be promptly and carefully disposed of. A well-planned baiting and trapping policy should be in place to effectively control rodents.

Only selected people should enter the hog houses

In any case, the number of persons entering the hog house must be kept as low as possible. Farmworkers should be trained in the principles of hygiene. They should wear adequate clothing (waterproof boots and protective overalls) that can be easily cleaned/laundered and disinfected. The clothes/shoes should always be used only at this site. Thorough hand washing and the disinfection of the boots when entering and leaving the pig unit are a must.

If visits are necessary, the visitors should take the same measures as the farm workers. And, of course, they should not have had contact with another pig farm during the last 48 hours.

Keep pens, farm equipment, and vehicles clean!

Farm equipment should not be shared with other farms. If this cannot be avoided, it must be cleaned and disinfected before re-entering the farm. Also, the vehicles for the transport of the animals must be cleaned and disinfected as soon as possible after usage, as contaminated transporters always pose the risk of infection.

Feed should be Salmonella-free!

To get high feed quality, the feed should be purchased from feed mills/sources with a well-functioning bacterial control to guarantee the absence of Salmonella. It is essential that birds, domestic and wild animals cannot enter the feed stores.
It is also advised to keep dry feed dry as possibly contaminating Salmonella can multiply in such humid conditions. Additionally, all feed bins and delivery pipes for dry and wet feed must be consciously cleaned, and the damp feed pipes also disinfected.
The change from pellets to mash could be helpful as the pellets facilitate Salmonella colonization by stimulating the secretion of mucins (Hedemann et al., 2005).

For sanitation of the feed, we offer organic acids (Acidomix product range) or mixtures of organic acids and formaldehyde in countries where formaldehyde products are allowed (Formycine) to decrease the pathogenic load of the feed materials. In vitro trials show the effectiveness of the products:

For the in vitro trial with Formycine, autoclaved feed samples were inoculated with Salmonella enteritidis serovar Typhimurium DSM 19587 strain to reach a Salmonella contamination of 10⁶ CFU/g of feed. After incubating at room temperature for three hours, Formycine Liquido was added to the contaminated feed samples at 0, 500, 1000, and 2000 ppm. The control and inoculated feed samples were further incubated at room temperature, and Salmonella counts (CFU/g) were carried out at 24, 48, 72 hours and on day 15. The limit of Salmonella detection was set at 100 CFU/g (10²). Results are shown in figure 2.

Fig. 2: Effect of treatment time and different inclusion levels of Formycine Liquido on the Salmonella count in feed

As important as uncontaminated feed is clean water for drinking. It can be achieved by taking the water from a main or a bacteriologically controlled water borehole. Regular cleaning/disinfection of the tanks, pipes, and drinkers is essential.

Bedding should be Salmonella-free

Straw material containing feces of other animals (rodents, pets) always carries the risk of Salmonella contamination. Also, wet or moldy bedding is not recommended because it is an additional challenge for the animal. To optimize the quality of bedding, the straw should be bought from reliable and as few as possible sources. The material must be stored dry and as far as practicable from the pig buildings (Ministry of Agriculture, Fisheries and Food & Scottish Executive Rural Affairs Department, 2000).

Vaccination is a beneficial measure

For the control of Salmonella in swine herds, vaccination is an effective tool. De Ridder et al. (2013) showed that an attenuated vaccine reduced the transmission of Salmonella Typhimurium in pigs. The vaccination with an attenuated S. Typhimurium strain, followed by a booster vaccination with inactivated S. Cholerasuis, showed better effects than an inactivated S. Cholerasuis vaccine alone (Alborali et al., 2017). Bearson et al. (2017) could delimitate transmission through less shedding and protect the animals against systemic disease.
To achieve the best effects, the producer must understand the diversity of Salmonella serovars to choose the most promising vaccination strategy (FSIS, 2023).

2. How to minimize the spreading of Salmonella on the farm?

If there are already cases of Salmonella on the farm, infected animals must be separated from the rest of the herd. Small batch sizes are beneficial, as well as not mixing different litters after weaning. If feasible, separate units for different production phases with an all-in/all-out system could break the reinfection cycle and help reduce Salmonella contamination on the farm. And also in this case, vaccination is helpful.

Salmonella doesn’t like acid conditions

An effective tool is acidifying the feed with organic acids, as Salmonella doesn’t like acid conditions. A trial was conducted with Acidomix AFG and Acidomix AFL to show their effects against Salmonella. For the test, 10⁵ CFU/g of Salmonella enterica ser. Typhimurium was added to feed containing 1000 ppm, 2000 ppm, and 3000 ppm of Acidomix AFG or AFL. The stomach and intestine were simulated in vitro by adjusting the pH with HCl and NaHCO3 as follows:
Stomach              2.8
Intestine              6.8-7.0

After the respective incubation, the microorganisms were recovered from feed and plated on an appropriate medium for CFU counting. The results are shown in figures 3 and 4.

Figures 3 + 4: Effects of different concentrations of Acidomix AFG and Acidomix AFL against Salmonella enterica ser. Typhimurium in feed

Phytomolecules can support pigs against Salmonella

Plant compounds or phytomolecules can also be used against Salmonella in pigs. Some examples of phytomolecules to be used are Piperine, Allicin, Eugenol, and Carvacrol. Eugenol, e.g., increases the permeability of the Salmonella membrane, disrupts the cytoplasmic membrane, and inhibits the production of bacterial virulence factors (Keita et al., 2022; Mak et al., 2019). Thymol and Carvacrol interact with the cell membrane by H bonding, also resulting in a higher permeability.

An already published in vitro trial conducted with our product Ventar D also showed excellent effects against Salmonella while sparing the beneficial gut flora. A further trial once more demonstrated the susceptibility of Salmonella to Ventar D. It showed that Ventar D controls Salmonella by suppressing their motility and, at higher concentrations, inactivating the cells (see figures 5 + 6):

Figure 5: S. enterica motility test: on the left side – control; on the right side – motility medium containing.750 µg/mL of Ventar

Fig 6 . Disk diffusion assay employing S. enterica. upper left side – disk containing 10 µL of Ventar; upper right – 5 µL; lower left – control; lower right – 1µL.

In addition to the direct Salmonella-reducing effect, essential oils / secondary plant compounds / phytomolecules improve digestive enzyme activity and digestion, leading to increased nutrient absorption and better feed conversion (Windisch et al., 2008).

3. How can the farmer keep Salmonella contamination low in the slaughterhouse?

In general, the slaughterhouse personnel is responsible for adequate hygiene management to prevent contamination of carcasses and meat. However, also the farmer can make his contribution to maintain the risk of contamination in the slaughterhouse as low as possible. A study by Vieira-Pinto (2006) revealed that one Salmonella-positive pig can contaminate several other carcasses.

According to a trial conducted by Hurd et al. (2002), infection and, therefore, “contamination” of other pigs can rapidly occur, meaning that cross-contamination is a topic during transport to the slaughterhouse and in the lairages when the pigs come together with animals from other farms. The stress to which the pigs are exposed influences physiological and biochemical processes. The microbiome and animal’s immunity are affected, leading to higher excretion of Salmonella during transport and in the lairages. So, the animals should not be stressed during loading and unloading or transportation. The trailer poses a further risk of infection if it was not cleaned and disinfected before. So, reliable people who treat the animals well and keep their trailers clean should be chosen for transportation.

Pig producers are obliged to keep Salmonella in check – phytomolecules can help

At least in the EU, pig producers have the big duty to keep Salmonella low in their herds; otherwise, they will have financial losses. They are not only responsible for their farm, but also the slaughterhouses count on them. Besides the standard strict hygiene management and vaccination, farmers can use products provided by the industry to sanitize feed but also to support their animals directly with phytomolecules acting against pathogens and supporting gut health.

All these measures together should be a solution to the immense challenge of Salmonella, to protect people and prevent economic losses.

References:

Alborali, Giovanni Loris, Jessica Ruggeri, Michele Pesciaroli, Nicola Martinelli, Barbara Chirullo, Serena Ammendola, Andrea Battistoni, Maria Cristina Ossiprandi, Attilio Corradi, and Paolo Pasquali. “Prime-Boost Vaccination with Attenuated Salmonella Typhimurium Δznuabc and Inactivated Salmonella Choleraesuis Is Protective against Salmonella Choleraesuis Challenge Infection in Piglets.” BMC Veterinary Research 13, no. 1 (2017): 284. https://doi.org/10.1186/s12917-017-1202-5.

Balaji, R, K J Wright, C M Hill, S S Dritz, E L Knoppel, and J E Minton. “Acute Phase Responses of Pigs Challenged Orally with Salmonella Typhimurium.” Journal of Animal Science 78, no. 7 (2000): 1885. https://doi.org/10.2527/2000.7871885x.

Bearson, Bradley L, Shawn M. Bearson, Brian W Brunelle, Darrell O Bayles, In Soo Lee, and Jalusa D Kich. “Salmonella Diva Vaccine Reduces Disease, Colonization, and Shedding Due to Virulent S. Typhimurium Infection in Swine.” Journal of Medical Microbiology 66, no. 5 (2017): 651–61. https://doi.org/10.1099/jmm.0.000482.

Brenner Michael, G, M Cardoso, and S Schwarz. “Molecular Analysis of Salmonella Enterica Subsp. Enterica Serovar Agona Isolated from Slaughter Pigs.” Veterinary Microbiology 112, no. 1 (2006): 43–52. https://doi.org/10.1016/j.vetmic.2005.10.011.

Chen, P.-L., C.-M. Chang, C.-J. Wu, N.-Y. Ko, N.-Y. Lee, H.-C. Lee, H.-I. Shih, C.-C. Lee, R.-R. Wang, and W.-C. Ko. “Extraintestinal Focal Infections in Adults with Non-typhoid Salmonella Bacteraemia: Predisposing Factors and Clinical Outcome.” Journal of Internal Medicine 261, no. 1 (2007): 91–100. https://doi.org/10.1111/j.1365-2796.2006.01748.x.

Chiu, Cheng-Hsun, Lin-Hui Su, and Chishih Chu. “Salmonella EntericaSerotype Choleraesuis: Epidemiology, Pathogenesis, Clinical Disease, and Treatment.” Clinical Microbiology Reviews 17, no. 2 (2004): 311–22. https://doi.org/10.1128/cmr.17.2.311-322.2004.

De Ridder, L., D. Maes, J. Dewulf, F. Pasmans, F. Boyen, F. Haesebrouck, E. Méroc, P. Butaye, and Y. Van der Stede. “Evaluation of Three Intervention Strategies to Reduce the Transmission of Salmonella Typhimurium in Pigs.” The Veterinary Journal 197, no. 3 (2013): 613–18. https://doi.org/10.1016/j.tvjl.2013.03.026.

Deane, Annette, Declan Murphy, Finola C. Leonard, William Byrne, Tracey Clegg, Gillian Madigan, Margaret Griffin, John Egan, and Deirdre M. Prendergast. “Prevalence of Salmonella spp. in Slaughter Pigs and Carcasses in Irish Abattoirs and Their Antimicrobial Resistance.” Irish Veterinary Journal 75, no. 1 (2022). https://doi.org/10.1186/s13620-022-00211-y.

Edel, W., M. Schothorst, P. A. Guinée, and E. H. Kampelmacher. “Effect of Feeding Pellets on the Prevention and Sanitation of Salmonella Infections in Fattening Pigs1.” Zentralblatt für Veterinärmedizin Reihe B 17, no. 7 (2010): 730–38. https://doi.org/10.1111/j.1439-0450.1970.tb01571.x.

EFSA. “Salmonella.” European Food Safety Authority. Accessed August 7, 2023. https://www.efsa.europa.eu/en/topics/topic/salmonella.

Elbediwi, Mohammed, Daiwei Shi, Silpak Biswas, Xuebin Xu, and Min Yue. “Changing Patterns of Salmonella Enterica Serovar Rissen from Humans, Food Animals, and Animal-Derived Foods in China, 1995–2019.” Frontiers in Microbiology 12 (2021). https://doi.org/10.3389/fmicb.2021.702909.

Elnekave, Ehud, Samuel Hong, Alison E Mather, Dave Boxrud, Angela J Taylor, Victoria Lappi, Timothy J Johnson, et al. “Salmonella Enterica Serotype 4,[5],12:I:- In Swine in the United States Midwest: An Emerging Multidrug-Resistant Clade.” Clinical Infectious Diseases 66, no. 6 (2018): 877–85. https://doi.org/10.1093/cid/cix909.

FCC Consortium. “Final Report – Food Safety.” European Commission, 2010. https://food.ec.europa.eu/system/files/2016-10/biosafety_food-borne-disease_salmonella_fattening-pigs_slaughthouse-analysis-costs.pdf.

Ferrari, Rafaela G., Denes K. Rosario, Adelino Cunha-Neto, Sérgio B. Mano, Eduardo E. Figueiredo, and Carlos A. Conte-Junior. “Worldwide Epidemiology of Salmonella serovars in Animal-Based Foods: A Meta-Analysis.” Applied and Environmental Microbiology 85, no. 14 (2019). https://doi.org/10.1128/aem.00591-19.

“FSIS Guideline to Control Salmonella in Swine Slaughter and Pork Processing Establishments.” FSIS Guideline to Control Salmonella in Swine Slaughter and Pork Processing Establishments | Food Safety and Inspection Service. Accessed August 14, 2023. https://www.fsis.usda.gov/guidelines/2023-0003.

Gal-Mor, Ohad, Erin C. Boyle, and Guntram A. Grassl. “Same Species, Different Diseases: How and Why Typhoidal and Non-Typhoidal Salmonella Enterica Serovars Differ.” Frontiers in Microbiology 5 (2014). https://doi.org/10.3389/fmicb.2014.00391.

González-Santamarina, Belén, Silvia García-Soto, Helmut Hotzel, Diana Meemken, Reinhard Fries, and Herbert Tomaso. “Salmonella Derby: A Comparative Genomic Analysis of Strains from Germany.” Frontiers in Microbiology 12 (2021). https://doi.org/10.3389/fmicb.2021.591929.

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Hauser, Elisabeth, Erhard Tietze, Reiner Helmuth, Ernst Junker, Kathrin Blank, Rita Prager, Wolfgang Rabsch, Bernd Appel, Angelika Fruth, and Burkhard Malorny. “Pork Contaminated with            Salmonella            Enterica            Serovar 4,[5],12:I:−, an Emerging Health Risk for Humans.” Applied and Environmental Microbiology 76, no. 14 (2010): 4601–10. https://doi.org/10.1128/aem.02991-09.

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Vieira-Pinto, M, R Tenreiro, and C Martins. “Unveiling Contamination Sources and Dissemination Routes of Salmonella Sp. in Pigs at a Portuguese Slaughterhouse through Macrorestriction Profiling by Pulsed-Field Gel Electrophoresis.” International Journal of Food Microbiology 110, no. 1 (2006): 77–84. https://doi.org/10.1016/j.ijfoodmicro.2006.01.046.

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By Dr Merideth Parke BVSc, Regional Technical Manager Swine, EW Nutrition

We care for our animals, and antibiotics are a crucial component in the management of disease due to susceptible pathogens, supporting animal health and welfare.  However, the administration of antibiotics in pig farming has become a common practice to prevent bacterial infections, reduce economic losses, and increase productivity.

All antibiotic applications have collateral consequences of significance, bringing a deeper consideration to their non-essential application. This article aims to challenge the choice to administer antibiotics by exploring the broader impact that antibiotics have on animal and human health, economies, and the environment.

Antibiotics disrupt microbial communities

Antibiotics do not specifically target pathogenic bacteria. By impacting beneficial microorganisms, they disrupt the natural balance of microbial communities within animals. They reduce the microbiota diversity and abundance of all susceptible bacteria – beneficial and pathogenic ones… many of which play crucial roles in digestion, brain function, the immune system, and respiratory and overall health. Resulting microbiota imbalances may present themselves in animals showing health performance changes associated with non-target systems, including the nasal, respiratory, or gut microbiome^{10, 9, 16}. The gut-respiratory microbiome axis is well-established in mammals. Gut microbiota health, diversity, and nutrient supply directly impact respiratory health and function¹⁵. In pigs specifically, the modulation of the gut microbiome is being considered as an additional tool in the control of respiratory diseases such as PRRS due to the link between the digestion of nutrients, systemic immunity, and response to pulmonary infections¹².

The collateral effect of antibiotic administration disrupting not only the microbial communities throughout the animal but also linked body systems needs to be considered significant in the context of optimal animal health, welfare, and productivity.

Antibiotic use can lead to the release of toxins

The consideration of the pathogenesis of individual bacteria is critical to mitigate potential for direct collateral effects associated with antibiotic administration. For example, in cases of toxin producing bacteria, when animals are medicated either orally or parenterally, mortality may increase due to the associated release of toxins when large numbers of toxin producing bacteria are killed quickly³.

Modulation of the brain function can be critical

Numerous animal studies have investigated the modulatory role of intestinal microbes on the gut-brain axis. One identified mechanism seen with antibiotic-induced changes in fecal microbiota is the decreased concentrations of hypothalamic neurotransmitter precursors, 5-hydroxytryptamine (serotonin), and dopamine⁶. Neurotransmitters are essential for communication between the nerve cells. Animals with oral antibiotic-induced microbiota depletion have been shown to experience changes in brain function, such as spatial memory deficits and depressive-like behaviors.

Processing of waste materials can be impacted

Anaerobic treatment technology is well accepted as a feasible management process for swine farm wastewater due to its relatively low cost with the benefit of bioenergy production. Additionally, the much smaller volume of sludge remaining after anaerobic processing further eases the safe disposal and decreases the risk associated with the disposal of swine waste containing residual antibiotics⁵.

The excretion of antibiotics in animal waste, and the resulting presence of antibiotics in wastewater, can impact the success of anaerobic treatment technologies, which already could be demonstrated by several studies^{8, 13}. The degree to which antibiotics affect this process will vary by type, combination, and concentration. Furthermore, the presence of antibiotics within the anaerobic system may result in a population shift towards less sensitive microbes or the development of strains with antibiotic-resistant genes^{1, 14}.

Antibiotics can be transferred to the human food chain

Regulatory authorities specify detailed withdrawal periods after antibiotic treatment. However, residues of antibiotics and their metabolites may persist in animal tissues, such as meat and milk, even after this period. These residues can enter the human food chain if not adequately monitored and controlled.

Prolonged exposure to low levels of antibiotics through the consumption of animal products may contribute to the emergence of antibiotic-resistant bacteria in humans, posing a significant public health risk.

Contamination of the environment

As already mentioned before, the administration of antibiotics to livestock can result in the release of these compounds into the environment. Antibiotics can enter the soil, waterways, and surrounding ecosystems through excretions from treated animals, inappropriate disposal of manure, and runoff from agricultural fields. Once in the environment, antibiotics can contribute to the selection and spread of antibiotic-resistant bacteria in natural bacterial communities. This contamination poses a potential risk to wildlife, including birds, fish, and other aquatic organisms, as well as the broader ecological balance of affected ecosystems.

Every use of antibiotics can create resistance

One of the widely researched concerns associated with antibiotic use in livestock is the development of antibiotic resistance. The development of AMR does not require prolonged antibiotic use and, along with other collateral effects, also occurs when antibiotics are used within recommended therapeutic or preventive applications.

Gene mutations can supply bacteria with abilities that make them resistant to certain antibiotics (e.g., a mechanism to destroy or discharge the antibiotic). This resistance can be transferred to other microorganisms, as seen with the effect of carbadox on Escherichia coli⁷ and Salmonella enterica² and the carbadox and metronidazole effect on Brachyspira hyodysenteriae¹⁶. Additionally, there is an indication that the zinc resistance of Staphylococcus of animal origin is associated with the methicillin resistance coming from humans⁴.

Consequently, the effectiveness of antibiotics in treating infections in target animals becomes compromised, and the risk of exposure to resistant pathogens for in-contact animals and across species increases, including humans.

Alternative solutions are available

To successfully minimize the collateral effects of antibiotic administration in livestock, a unified strategy with support from all stakeholders in the production system is essential. The European Innovation Partnership – Agriculture¹¹ concisely summarizes such a process as requiring…

1. Changing human mindsets and habits: this is the first and defining step to successful antimicrobial reduction
2. Improving pig health and welfare: Prevention of disease with optimal husbandry, hygiene, biosecurity, vaccination programs, and nutritional support.
3. Effective antibiotic alternatives: for this purpose, phytomolecules, pro/pre-biotics, organic acids, and immunoglobulins are considerations.

In general, implementing responsible antibiotic stewardship practices is paramount. This includes limiting antibiotic use to the treatment of diagnosed infections with an effective antibiotic, and eliminating their use as growth promotors or for prophylactic purposes.

Keeping the balance is of crucial importance

While antibiotics play a crucial role in ensuring the health and welfare of livestock, their extensive administration in the agricultural industry has collateral effects that cannot be ignored. The development of antibiotic resistance, environmental contamination, disruption of microbial communities, and the potential transfer of antibiotic residues to food pose significant challenges.

Adopting responsible antibiotic stewardship practices, including veterinary oversight, disease prevention programs, optimal animal husbandry practices, and alternatives to antibiotics, can strike a balance between animal health, efficient productive performance, and environmental and human health concerns.

The collaboration of stakeholders, including farmers, veterinarians, policymakers, industry and consumers, is essential in implementing and supporting these measures to create a sustainable and resilient livestock industry.

References

1. Angenent, Largus T., Margit Mau, Usha George, James A. Zahn, and Lutgarde Raskin. “Effect of the Presence of the Antimicrobial Tylosin in Swine Waste on Anaerobic Treatment.” Water Research 42, no. 10–11 (2008): 2377–84. https://doi.org/10.1016/j.watres.2008.01.005.
2. Bearson, Bradley L., Heather K. Allen, Brian W. Brunelle, In Soo Lee, Sherwood R. Casjens, and Thaddeus B. Stanton. “The Agricultural Antibiotic Carbadox Induces Phage-Mediated Gene Transfer in Salmonella.” Frontiers in Microbiology 5 (2014). https://doi.org/10.3389/fmicb.2014.00052.
3. Castillofollow, Manuel Toledo, Rocío García Espejofollow, Alejandro Martínez Molinafollow, María Elena  Goyena Salgadofollow, José Manuel Pintofollow, Ángela Gallardo Marínfollow, M. Toledo, et al. “Clinical Case: Edema Disease – the More I Medicate, the More Pigs Die!” $this->url_servidor, October 15, 2021. https://www.pig333.com/articles/edema-disease-the-more-i-medicate-the-more-pigs-die_17660/.
4. Cavaco, Lina M., Henrik Hasman, Frank M. Aarestrup, Members of MRSA-CG:, Jaap A. Wagenaar, Haitske Graveland, Kees Veldman, et al. “Zinc Resistance of Staphylococcus Aureus of Animal Origin Is Strongly Associated with Methicillin Resistance.” Veterinary Microbiology 150, no. 3–4 (2011): 344–48. https://doi.org/10.1016/j.vetmic.2011.02.014.
5. Cheng, D.L., H.H. Ngo, W.S. Guo, S.W. Chang, D.D. Nguyen, S. Mathava Kumar, B. Du, Q. Wei, and D. Wei. “Problematic Effects of Antibiotics on Anaerobic Treatment of Swine Wastewater.” Bioresource Technology 263 (2018): 642–53. https://doi.org/10.1016/j.biortech.2018.05.010.
6. Köhler, Bernd, Helge Karch, and Herbert Schmidt. “Antibacterials That Are Used as Growth Promoters in Animal Husbandry Can Affect the Release of Shiga-Toxin-2-Converting Bacteriophages and Shiga Toxin 2 from Escherichia Coli Strains.” Microbiology 146, no. 5 (2000): 1085–90. https://doi.org/10.1099/00221287-146-5-1085.
7. Loftin, Keith A., Cynthia Henny, Craig D. Adams, Rao Surampali, and Melanie R. Mormile. “Inhibition of Microbial Metabolism in Anaerobic Lagoons by Selected Sulfonamides, Tetracyclines, Lincomycin, and Tylosin Tartrate.” Environmental Toxicology and Chemistry 24, no. 4 (2005): 782–88. https://doi.org/10.1897/04-093r.1.
8. Looft, Torey, Heather K Allen, Brandi L Cantarel, Uri Y Levine, Darrell O Bayles, David P Alt, Bernard Henrissat, and Thaddeus B Stanton. “Bacteria, Phages and Pigs: The Effects of in-Feed Antibiotics on the Microbiome at Different Gut Locations.” The ISME Journal 8, no. 8 (2014a): 1566–76. https://doi.org/10.1038/ismej.2014.12.
9. Looft, Torey, Heather K. Allen, Thomas A. Casey, David P. Alt, and Thaddeus B. Stanton. “Carbadox Has Both Temporary and Lasting Effects on the Swine Gut Microbiota.” Frontiers in Microbiology 5 (2014b). https://doi.org/10.3389/fmicb.2014.00276.
10. Nasralla, Meisoon. “EIP-Agri Concept.” EIP-AGRI – European Commission, September 11, 2017. https://ec.europa.eu/eip/agriculture/en/eip-agri-concept.html.
11. Niederwerder, Megan C. “Role of the Microbiome in Swine Respiratory Disease.” Veterinary Microbiology 209 (2017): 97–106. https://doi.org/10.1016/j.vetmic.2017.02.017.
12. Poels, J., P. Van Assche, and W. Verstraete. “Effects of Disinfectants and Antibiotics on the Anaerobic Digestion of Piggery Waste.” Agricultural Wastes 9, no. 4 (1984): 239–47. https://doi.org/10.1016/0141-4607(84)90083-0.
13. Shimada, Toshio, Julie L. Zilles, Eberhard Morgenroth, and Lutgarde Raskin. “Inhibitory Effects of the Macrolide Antimicrobial Tylosin on Anaerobic Treatment.” Biotechnology and Bioengineering 101, no. 1 (2008): 73–82. https://doi.org/10.1002/bit.21864.
14. Sikder, Md. Al, Ridwan B. Rashid, Tufael Ahmed, Ismail Sebina, Daniel R. Howard, Md. Ashik Ullah, Muhammed Mahfuzur Rahman, et al. “Maternal Diet Modulates the Infant Microbiome and Intestinal Flt3l Necessary for Dendritic Cell Development and Immunity to Respiratory Infection.” Immunity 56, no. 5 (May 9, 2023): 1098–1114. https://doi.org/10.1016/j.immuni.2023.03.002.
15. Slifierz, Mackenzie Jonathan. “The Effects of Zinc Therapy on the Co-Selection of Methicillin-Resistance in Livestock-Associated Staphylococcus Aureus and the Bacterial Ecology of the Porcine Microbiota,” 2016.
16. Stanton, Thaddeus B., Samuel B. Humphrey, Vijay K. Sharma, and Richard L. Zuerner. “Collateral Effects of Antibiotics: Carbadox and Metronidazole Induce VSH-1 and Facilitate Gene Transfer among Brachyspira Hyodysenteriae” Applied and Environmental Microbiology 74, no. 10 (2008): 2950–56. https://doi.org/10.1128/aem.00189-08.

By Lea Poppe, Regional Technical Manager On-Farm Solutions Europe, and Dr. Inge Heinzl, Editor

One of the ten global public health threats is antimicrobial resistance (AMR). Jim O’Neill predicted 10 million people dying from AMR annually by 2050 (O’Neill, 2016). The following article will show the causes of antimicrobial resistance and how antibodies from the egg could help mitigate the problem of AMR.

Global problem of AMR results from the incorrect use of antimicrobials

Antimicrobial substances are used to prevent and cure diseases in humans, animals, and plants and include antibiotics, antivirals, antiparasitics, and antifungals. The use of these medicines does not always happen consciously, partially due to ignorance and partially for economic reasons.

There are various possibilities for the wrong therapy

1. The use of antibiotics against diseases that household remedies could cure. A recently published German study (Merle et al., 2023) confirmed the linear relationship between treatment frequency and resistant scores in calves younger than eight months.
2. The use of antibiotics against viral diseases: antibiotics only act against bacteria and not against viruses. Flu, e.g., is caused by a virus, but doctors often prescribe an antibiotic.
3. Using broad-spectrum antibiotics instead of determining an antibiogram and applying a specific antibiotic.
4. A too-long treatment with antimicrobials so that the microorganisms have the time to adapt. For a long time, the only mistake you could make was to stop the antibiotic therapy too early. Today, the motto is “as short as possible”.

Let’s take the example of neonatal calf diarrhea, one of the most common diseases with a high economic impact. Calf diarrhea can be caused by a wide range of bacteria, viruses, or parasites. This infectious form can be a complication of non-infectious diarrhea caused by dietary, psychological, and environmental stress (Uetake, 2012). The pathogens causing diarrhea in calves can vary with the region. In Switzerland and the UK, e.g., rotaviruses and cryptosporidia are the most common pathogens, whereas, in Germany, E. coli is also one of the leading causes. To minimize the occurrence of AMR, it is always crucial to know which pathogen is behind the disease.

Prophylactic use of antibiotics is still a problem

1. The use of low doses of antibiotics to promote growth. This use has been banned in the EU now for 17 years now, but in other parts of the world, it is still common practice. Especially in countries with low hygienic standards, antibiotics show high efficacy.
2. The preventive use of antibiotics to help, e.g., piglets overcome the critical step of weaning or to support purchased animals for the first time in their new environment. Antibiotics reduce pathogenic pressure, decrease the incidence of diarrhea, and ensure the maintenance of growth.
3. Within the scope of prophylactic use of antimicrobials, also group treatment must be mentioned. In veal calves, group treatments are far more common than individual treatments (97.9% of all treatments), as reported in a study documenting medication in veal calf production in Belgium and the Netherlands. Treatment indications were respiratory diseases (53%), arrival prophylaxis (13%), and diarrhea (12%). On top, the study found that nearly half of the antimicrobial group treatment was underdosed (43.7%), and a large part (37.1%) was overdosed.

However, in several countries, consumers request reduced or even no usage of antibiotics (“No Antibiotics Ever” – NAE), and animal producers must react.

Today’s mobility enables the spreading of AMR worldwide

Bacteria, viruses, parasites, and fungi that no longer respond to antimicrobial therapy are classified as resistant. The drugs become ineffective and, therefore, the treatment of disease inefficient or even impossible. All the different usages mentioned before offer the possibility that resistant bacteria/microorganisms will occur and proliferate. Due to global trade and the mobility of people, drug-resistant pathogens are spreading rapidly throughout the world, and common diseases cannot be treated anymore with existing antimicrobial medicines like antibiotics. Standard surgeries can become a risk, and, in the worst case, humans die from diseases once considered treatable. If new antibiotics are developed, their long-term efficacy again depends on their correct and limited use.

Different approaches are taken to fight AMR

There have already been different approaches to fighting AMR. As examples, the annually published MARAN Report compiled in the Netherlands, the EU ban on antibiotic growth promoters in 2006, “No antibiotics ever (NAE) programs” in the US, or the annually published “Antimicrobial resistance surveillance in Europe” can be mentioned. One of the latest approaches is an advisory “One Health High-Level Expert Panel” (OHHLEP) founded by the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), the United Nations Environment Program (UNEP), and the World Health Organization (WHO) in May 2021. As AMR has many causes and, consequently, many players are involved in its reduction, the OHHLEP wants to improve communication and collaboration between all sectors and stakeholders. The goal is to design and implement programs, policies, legislations, and research to improve human, animal, and environmental health, which are closely linked. Approaches like those mentioned help reduce the spread of resistant pathogens and, with this, remain able to treat diseases in humans, animals, and plants.

On top of the pure health benefits, reducing AMR improves food security and safety and contributes to achieving the Sustainable Development Goals (e.g., zero hunger, good health and well-being, and clean water).

Prevention is better than treatment

Young animals like calves, lambs, and piglets do not receive immunological equipment in the womb and need a passive immune transfer by maternal colostrum. Accordingly, optimal colostrum management is the first way to protect newborn animals from infection, confirmed by the general discussion on the Failure of Passive Transfer: various studies suggest that calves with poor immunoglobulin supply suffer from diarrhea more frequently than calves with adequate supply.

Especially during the immunological gap when the maternal immunoglobulins are decreasing and the own immunocompetence is still not fully developed, it is crucial to have a look at housing, stress triggers, biosecurity, and the diet to reduce the risk of infectious diseases and the need for treatments.

Immunoglobulins from eggs additionally support young animals

Also, if newborn animals receive enough colostrum in time and if everything goes optimally, the animals suffer from two immunity gaps: the first one occurs just after birth before the first intake of colostrum, and the second one occurs when the maternal antibodies decrease, and the immune system of the young animal is still not developed completely. These immunity gaps raise the question of whether something else can be done to support newborns during their first days of life.

The answer was provided by Felix Klemperer (1893), a German internist researching immunity. He found that hens coming in contact with pathogens produce antibodies against these agents and transfer them to the egg. It is unimportant if the pathogens are relevant for chickens or other animals. In the egg, the immunoglobulins usually serve as an immune starter kit for the chick.

Technology enables us today to produce a high-value product based on egg powder containing natural egg immunoglobulins (IgY – immunoglobulins from the yolk). These egg antibodies mainly act in the gut. There, they recognize and tie up, for example, diarrhea-causing pathogens and, in this way, render them ineffective.

The efficacy of egg antibodies was demonstrated in different studies (Kellner et al., 1994; Erhard et al., 1996; Ikemori et al., 1997; Yokoyama et al., 1992; Marquart, 1999; Yokoyama et al., 1997) for piglets and calves.

Trial proves high efficacy of egg immunoglobulins in piglets

One trial conducted in Germany showed promising results concerning the reduction of mortality in the farrowing unit. For the trial, 96 sows and their litters were divided into three groups with 32 sows each. Two of the groups orally received a product containing egg immunoglobulins, the EP -1 + 3 group on days 1 and 3 and the EP – 1 + 2 + 3 group on the first three days. The third group served as a control. Regardless of the frequency of application, the egg powder product was very supportive and significantly reduced mortality compared to the control group. The measure resulted in 2 additionally weaned piglets than in the control group.

Egg immunoglobulins support young dairy calves

IgY-based products were also tested in calves to demonstrate their efficacy. In a field trial conducted on a Portuguese dairy farm with 12 calves per group, an IgY-containing oral application was compared to a control group without supplementation. The test product was applied on the day of birth and the two consecutive days. Key observation parameters during a two-week observation period were diarrhea incidence, onset, duration, and antibiotic treatments, the standard procedure on the trial farm in case of diarrhea. On-farm tests to check for the pathogenic cause of diarrhea were not part of the farm’s standards.

In this trial, 10 of 12 calves in the control group suffered from diarrhea, but in the trial group, only 5 calves. Total diarrhea and antibiotic treatment duration in the control group was 37 days (average 3.08 days/animal), and in the trial group, only 7 days (average 0.58 days/animal). Additionally, diarrhea in calves of the Globigen Calf Paste group started later, so the animals already had the chance to develop an at least minimally working immune system.

The supplement served as an effective tool to support calves during their first days of life and to reduce antibiotic treatments dramatically.

Conclusion

Antimicrobial reduction is one of the biggest tasks for global animal production. It must be done without impacting animal health and parameters like growth performance and general cost-efficacy. This overall demand can be supported with a holistic approach considering biosecurity, stress reduction, and nutritional support. Feed supplements such as egg immunoglobulins are commercial options showing great results and benefits in the field and making global animal production take the right direction in the future.

References upon request.

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

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

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

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

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

How to measure the feed conversion rate

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

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

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

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

Many factors influence the FCR

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

1. Species

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

Table 1: FCRs of different species

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

2. Sex, age, and growth phase

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

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

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

3. Health and gut health

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

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

4. Environment

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

5. Feed quantity, composition, and quality

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

Better FCR by increasing nutrient density and digestibility

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

Feed form and particle size play an important role

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

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

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

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

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

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

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

Molds and mycotoxins impair feed quality, but also animal health

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

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

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

Oxidation of fats also affects feed quality

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

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

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

Use adequate supplements to enhance FCR

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

1. Boost your animals’ gut health

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

Phytomolecules help stabilize the balance of the microbiome

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

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

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

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

Figure 2: FCR improvements for animals receiving Activo

Products mitigating the adverse effects of toxins

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

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

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

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

2. Improve nutrient utilization

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

Phytomolecules support the animal’s digestive system

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

Enzymes release more nutrients from feed

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

3. Be proactive about preserving feed quality

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

Antioxidants prevent feed oxidation

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

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

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

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

Inhibiting molds and keeping feed moisture

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

Conclusion

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

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

References

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

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

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

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

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

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

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

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

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

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

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

By Dr. Inge Heinzl, Editor, EW Nutrition

Nowadays, intensive livestock farming with high stocking densities causes stress in the animals and affects the immune system^{9, 13}. The increase in respiratory diseases with associated losses and costs is only one of the consequences. Due to antimicrobial resistance, antibiotics should only be used in critical cases, so effective alternatives are requested to support the animals.

Respiratory problems are a conjunction of several factors

It already has a name: PRDC or the Porcine Respiratory Disease Complex describes the cooperation of viruses, bacteria, and non-infectious factors such as environmental conditions (e.g., insufficient ventilation), stocking density, management (e.g., all-in-all-out only by pens and not for the whole house) and pig-specific factors such as age and genetics, altogether causing respiratory issues in pigs. Non-infectious factors such as high ammonia levels weaken the immune system and lay the foundation for, e.g., mycoplasmas which damage the ciliated epithelial cells in the upper respiratory tract, the first line of defense, and pave the way for PRRS viruses. They, on their part, enter the respiratory tract embedded in inhaled dust. There, they harm the macrophages and breach a further barrier of defense. Another pathfinder is the Porcine Circovirus 2 (PCV2), which destroys specific immune cells and leads to a generally higher susceptibility to infectious agents. Bacteria such as Pasteurella multocida or Streptococcus suis further on can cause secondary infections^{7, 20, 22}. Also, the combination of mycoplasma hyopneumoniae and porcine circovirus, both typically low pathogenic organisms, leads to severe respiratory disease¹⁵.

Restricted respiratory function impacts growth

The main tasks of the respiratory tract are to take in oxygen from the air and to pump out the CO₂ entailed by the catabolism of the tissue. In pigs, however, the respiratory tract is also responsible for thermoregulation, as pigs don’t have perspiration glands. The animals must get rid of excessive heat by rapid breathing. If the respiratory function is affected due to disease, thermoregulatory capacity is reduced. The resulting lower feed intake leads to decreased growth performance and less economic profit¹⁷. One of the first studies concerning this topic was conducted by Straw et al. (1989)²¹. They asserted that, with every 10 % more affected lung tissue, daily gain decreased by about 37g. This negative correlation between affected lung tissue and weight gain could be confirmed by Paz-Sánchez et al. (2021)¹⁸. They saw that animals with >10% lung parenchyma impacted by cranioventral bronchopneumonia needed a longer time to market (208.8 days vs. 200.8 days in the control), showed a lower carcass weight (74.1 kg vs. 77.7 kg in the control group) and, therefore, also a lower daily gain (500.8 g/day compared to 567.2 g/d). In another study, Pagot and co-workers (2007)¹⁶ observed 7000 pigs from 14 French farms. They saw a significant negative correlation (p<0.001) between the prevalence of pneumonia and growth and a weight gain loss of about 0.7 for each point of pneumonia increase.

Plant extracts support pigs with different modes of action

People have always used herbal substances to cure illnesses, be it willow bark for pain, chamomile for anti-inflammation or an upset stomach. Ribwort and thyme are used as cough suppressants, and eucalyptus and menthol help you breathe better. What is good for humans can also be used for pigs. To use plant extracts efficiently, it is crucial to know their specific modes of action. Due to their volatile nature, essential oils can directly reach the target site, the respiratory tract, via inhalation¹.

1.   Plant extracts can act as an antimicrobial

Many essential oils show some degree of antimicrobial activity. So, the oils of, e. g., oregano, tea tree, lemongrass, lemon myrtle, and clove are effective against a wide range of gram-positive and gram-negative bacteria. LeBel et al. (2019)¹² tested nine different oils against microorganisms causing respiratory issues in pigs. They found the oils of cinnamon, thyme, and winter savory the most effective against Streptococcus suis, Actinobacillus pleuropneumoniae, Actinobacillus suis, Bordetella bronchiseptica, Haemophilus parasuis, and Pasteurella multocida, with MICs and MBCs from 0.01 to 0.156%.

Not only the direct bactericidal effect is important. 1,8 cineol, e.g., although often considered to have only marginal or no antimicrobial activity¹⁰, effectively causes leakage of bacterial membranes² and allows other harmful substances to enter the bacterial cell. However, cineol possesses noted antiviral properties.

2.  Plant extracts can have mucolytic, spasmolytic, and antitussive effects

In the case of respiratory disease, mucolytic and spasmolytic characteristics of phytomolecules are decisive in allowing efficient respiration. Mucolytic substances dissolve the mucus, make it more liquid and facilitate the removal from the respiratory tract by the ciliated epithelium. As liquifying the mucus with essential oils or phytomolecules is related to local irritation, dosage and application form are of the highest importance⁵.

The “cleanup” is called mucociliary clearance. There are also substances that do not dissolve the mucus but stimulate the mucociliary apparatus itself and increase mucociliary transport velocity¹.

Spasmolytic activity on airway smooth muscle is shown, for example, by menthol⁸ or the essential oil of eucalyptus tereticornis⁴. Menthol showed antitussive effects¹¹.

3.   Plant extracts can have immune-modulatory and anti-inflammatory effects

If animals are suffering from a respiratory disease or are in danger of catching one, a supportive influence on the immune system is helpful. One thing is to make vaccination more effective. Mieres-Castro et al. (2021)¹⁴ figured out that the combined application of influenza vaccine and cineol to mice resulted in a longer survival time, less inflammation, less weight loss, a lower mortality rate, less pulmonary edema, and lower viral titers after a challenge with the virus seven days after the vaccination than the mice without cineol.

On the other hand, if the animals are already ill, strengthening their immune defense is essential. Li et al. (2012)¹³ showed that interleukin-6 concentration was lower (p<0.05) and the tumor necrosis factor-α level was higher (p<0.05) in the plasma of pigs fed a diet with 0.18% thymol and cinnamaldehyde than in the negative control group. Also, the lymphocyte proliferation for pigs fed the diet with thymol and cinnamaldehyde increased significantly compared with the negative control (p<0.05).

4.   Plant extracts can act as an antioxidant

There are respiratory diseases in which reactive oxygen species (ROS) play an important role. In these cases, the antioxidant activity of phytomolecules is of interest. Here again, Li et al. (2012)¹³ asserted that a diet with 0.18% thymol and cinnamaldehyde increased the total antioxidant capacity level (p<0.05) in pigs compared to a negative control group.

Can Baser & Buchbauer (2010) described eucalyptus oil containing 1,8-cineole, the monoterpene hydrocarbons α-pinene (10–12%), p-cymene, and α-terpinene, and the monoterpene alcohol linalool, is used to treat diseases of the respiratory tract in which ROS play an important role.

5.   Plant extracts reduce the production of ammonia

High concentration of ammonia in the pig house stresses the pigs’ respiratory tract and makes them susceptible to disease. Ammonia develops when feces and urine merge and the enzyme urease degrades them. Yucca extract, containing a high percentage of saponins, can reduce ammonia emissions in animal houses. Ehrlinger (2007)⁵ supposes that the glyco-components of the saponins bind ammonia and other harmful gases. Another explanation can be the decreased activity of urease shown in a trial with rats¹⁹ or the reduction of total nitrogen, urea nitrogen, and ammonia nitrogen in sow manure³.

6.   Plant extracts often show diverse modes of useful action against respiratory issues

Due to their natural task – protecting the plant – essential oils typically do not show only one beneficial activity for us. Camphene, for example, in Thymus vulgaris, shows expectorant, spasmolytic, and antimicrobial properties and is used in treating respiratory tract infections. Menthol can be effectively used in cases of asthma due to its bronchodilatory activity on smooth muscle, its interaction with cold receptors, and the respiratory drive. Menthol acts antitussive in low concentration, gives the impression of decongestion and reduces respiratory discomfort and sensations of dyspnea.

Cineol, on its part, acts antimicrobial, antitussive, bronchodilatory, mucolytic, and anti-inflammatory. It promotes ciliary transport and improves lung function^{1, 6}. Mucolytic, antioxidant, antiviral, and antibacterial activity is ascribed to thymol⁵.

Trial shows: phytomolecules help to keep respiratory diseases in check

A field study was conducted on a Philippine piglet farm with a history of chronic respiratory issues during the growing phase, with a morbidity of about 10-15%. In this study, a supplement for water containing phytomolecules that support animals against respiratory diseases (Grippozon) was tested. For the trial, 360 randomly selected 28-day-old pigs (average weight: 6.64±0.44 kg) were divided into two groups with 6 replications per group and 30 piglets per replication. All piglets came from sows raised antibiotic-free, and the piglets received antibiotics neither upon weaning except in case of symptoms (scouring: Baytril-1 mL/pig;  respiratory disease: Excede – 1mL/pig). All piglets received the same feed and a regular water therapy regimen:

Control group: no additional supplements
Grippozon group:  Addition of 250 mL of Grippozon per 1000 L of water

As parameters, the incidence of respiratory disease, final weight, daily gain, FCR, and antibiotic cost, were recorded.

The phytomolecules-containing product reduced the incidence of respiratory diseases by 52 %, leading to a 53% lower cost for antibiotic treatment. The animals showed better growth performance (600 g higher average weight and 13 g higher average daily gain), altogether resulting in an extra cost-benefit of 1.76 US$ per pig.

Reduction in disease and medication ensures healthier pigs in the Grippozon-supplemented group, reflected by better performance.

We have means at hand to reduce the use of antibiotics

Respiratory disease is a big problem in pigs. Due to the still high occurrence of antimicrobial resistance, it is essential to reduce antibiotic use as much as possible. Phytomolecules offer the possibility to strengthen the animals’ health so that they are less susceptible to disease or support them when they are already infected. With the help of phytomolecules, we can reduce antibiotic treatments and help keep antibiotics effective when their use is indispensable.

References

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