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 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

1. Can Baser , K. Hüsnü, and Gerhard Buchbauer. Handbook of Essential Oils: Science, Technology, and Applications. Boca Raton, FL: Taylor & Francis distributor, 2010.
2. Carson, Christine F., Brian J. Mee, and Thomas V. Riley. “Mechanism of Action of Melaleuca Alternifolia (Tea Tree) Oil on Staphylococcus Aureus Determined by Time-Kill, Lysis, Leakage, and Salt Tolerance Assays and Electron Microscopy.” Antimicrobial Agents and Chemotherapy 46, no. 6 (2002): 1914–20. https://doi.org/10.1128/aac.46.6.1914-1920.2002.
3. Chen, Fang, Yantao Lv, Pengwei Zhu, Chang Cui, Caichi Wu, Jun Chen, Shihai Zhang, and Wutai Guan. “Dietary Yucca Schidigera Extract Supplementation during Late Gestating and Lactating Sows Improves Animal Performance, Nutrient Digestibility, and Manure Ammonia Emission.” Frontiers in Veterinary Science 8 (2021). https://doi.org/10.3389/fvets.2021.676324.
4. Coelho-de-Souza, Lívia Noronha, José Henrique Leal-Cardoso, Francisco José de Abreu Matos, Saad Lahlou, and Pedro Jorge Magalhães. “Relaxant Effects of the Essential Oil of Eucalyptus Tereticornisand Its Main Constituent 1,8-Cineole on Guinea-Pig Tracheal Smooth Muscle.” Planta Medica 71, no. 12 (2005): 1173–75. https://doi.org/10.1055/s-2005-873173.
5. Ehrlinger, Miriam. “Phytogene Zusatzstoffe in der Tierernährung.” Dissertation, Tierärztliche Fakultät LMU, 2007.
6. Gelbe Liste Online. “Gelbe Liste Pharmindex Online.” Gelbe Liste. Accessed January 20, 2023. https://www.gelbe-liste.de/.
7. Hennig-Pauka, Isabell. “Atemwegserkrankungen: Schutz fängt schon bei Ferkeln an.” Der Hoftierarzt, January 13, 2021. https://derhoftierarzt.de/2021/01/atemwegserkrankungen-schutz-faengt-schon-bei-ferkeln-an/.
8. Ito, Satoru, Hiroaki Kume, Akira Shiraki, Masashi Kondo, Yasushi Makino, Kaichiro Kamiya, and Yoshinori Hasegawa. “Inhibition by the Cold Receptor Agonists Menthol and ICILIN of Airway Smooth Muscle Contraction.” Pulmonary Pharmacology & Therapeutics 21, no. 5 (2008): 812–17. https://doi.org/10.1016/j.pupt.2008.07.001.
9. Kim, K.H., E.S. Cho, K.S. Kim, J.E. Kim, K.H. Seol, S.J. Sa, Y.M. Kim, and Y.H. Kim. “Effects of Stocking Density on Growth Performance, Carcass Grade and Immunity of Pigs Housed in Sawdust Fermentative Pigsties.” South African Journal of Animal Science 46, no. 3 (2016): 294–301. https://doi.org/10.4314/sajas.v46i3.9.
10. Kotan, Recep, Saban Kordali, and Ahmet Cakir. “Screening of Antibacterial Activities of Twenty-One Oxygenated Monoterpenes.” Zeitschrift für Naturforschung C 62, no. 7-8 (2007): 507–13. https://doi.org/10.1515/znc-2007-7-808.
11. Laude, E.A., A.H. Morice, and T.J. Grattan. “The Antitussive Effects of Menthol, Camphor, and Cineole in Conscious Guinea-Pigs.” Pulmonary Pharmacology 7, no. 3 (1994): 179–84. https://doi.org/10.1006/pulp.1994.1021.
12. LeBel, Geneviève, Katy Vaillancourt, Philippe Bercier, and Daniel Grenier. “Antibacterial Activity against Porcine Respiratory Bacterial Pathogens and in Vitro Biocompatibility of Essential Oils.” Archives of Microbiology 201, no. 6 (2019): 833–40. https://doi.org/10.1007/s00203-019-01655-7.
13. Li, Xue, Xia Xiong, Xin Wu, Gang Liu, Kai Zhou, and Yulong Yin. “Effects of Stocking Density on Growth Performance, Blood Parameters and Immunity of Growing Pigs.” Animal Nutrition 6, no. 4 (2020): 529–34. https://doi.org/10.1016/j.aninu.2020.04.001.
14. Mieres-Castro, Daniel, Sunny Ahmar, Rubab Shabbir, and Freddy Mora-Poblete. “Antiviral Activities of Eucalyptus Essential Oils: Their Effectiveness as Therapeutic Targets against Human Viruses.” Pharmaceuticals 14, no. 12 (2021): 1210. https://doi.org/10.3390/ph14121210.
15. Opriessnig, T., L. G. Giménez-Lirola, and P. G. Halbur. “Polymicrobial Respiratory Disease in Pigs.” Animal Health Research Reviews 12, no. 2 (2011): 133–48. https://doi.org/10.1017/s1466252311000120.
16. Pagot, E., P. Keita, and A. Pommier. “Relationship between Growth during the Fattening Period and Lung Lesions at Slaughter in Swine.” Revue Méd. Vét., , , 5, 253-259 158, no. 5 (2007): 253–59.
17. Pallarés Martínez, Francisco José, Jaime Gómez Laguna, Inés Ruedas Torres, José María Sánchez Carvajal, Fernanda Isabel Larenas Muñoz, Irene Magdalena Rodríguez-Gómez, and Librado Carrasco Otero. “The Economic Impact of Pneumonia Processes in Pigs.” https://www.pig333.com. Pig333.com Professional Pig Community, December 14, 2020. https://www.pig333.com/articles/the-economic-impact-of-pneumonia-processes-in-pigs_16470/.
18. Paz-Sánchez, Yania, Pedro Herráez, Óscar Quesada-Canales, Carlos G. Poveda, Josué Díaz-Delgado, María del Quintana-Montesdeoca, Elena Plamenova Stefanova, and Marisa Andrada. “Assessment of Lung Disease in Finishing Pigs at Slaughter: Pulmonary Lesions and Implications on Productivity Parameters.” Animals 11, no. 12 (2021): 3604. https://doi.org/10.3390/ani11123604.
19. Preston, R. L., S. J. Bartle, T. May, and S. R. Goodall. “Influence of Sarsaponin on Growth, Feed and Nitrogen Utilization in Growing Male Rats Fed Diets with Added Urea or Protein.” Journal of Animal Science 65, no. 2 (1987): 481–87. https://doi.org/10.2527/jas1987.652481x.
20. Ruggeri, Jessica, Cristian Salogni, Stefano Giovannini, Nicoletta Vitale, Maria Beatrice Boniotti, Attilio Corradi, Paolo Pozzi, Paolo Pasquali, and Giovanni Loris Alborali. “Association between Infectious Agents and Lesions in Post-Weaned Piglets and Fattening Heavy Pigs with Porcine Respiratory Disease Complex (PRDC).” Frontiers in Veterinary Science 7 (2020). https://doi.org/10.3389/fvets.2020.00636.
21. Straw , B. E., V. K. Tuovinen, and M. Bigras-Poulin. “Estimation of the Cost of Pneumonia in Swine Herds.” J Am Vet Med Assoc. 1989 Dec 15;195(12):1702-6. 195, no. 12 (December 15, 1989): 1702–6.
22. White, Mark. “Porcine Respiratory Disease Complex (PRDC).” Livestock 16, no. 2 (2011): 40–42. https://doi.org/10.1111/j.2044-3870.2010.00025.x.

By Dr. Inge Heinzl, Editor, EW Nutrition

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

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

Weaning – a critical point in piglets’ life

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

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

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

The higher stomach pH is partly responsible for problems after weaning

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

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

1.  Lower activity of proteolytic enzymes

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

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

2. Expedited digesta transport

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

3. Proliferation of microorganisms

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

   Elevated stomach pH + incomplete immune system = diarrhea

Acidifiers can mitigate the adverse effects of weaning on piglets

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

What are acidifiers?

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

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

Organic acids: Commonly used with good results

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

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

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

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

Inorganic acids – the low-cost version

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

Salts are easier to handle

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

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

Blends

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

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

The main effects of acidifiers

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

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

1.    Improvement in gut health

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

1.1     Organic acids directly attack bacteria

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

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

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

1.1     Decreased pH reduces non-acid-tolerant pathogens

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

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

1.2     Recovery of eubiosis through reduction of substrate

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

2. Promotion of growth

2.1     Enhanced digestion of macronutrients

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

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

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

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

2.2     Improved utilization of minerals

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

Phytic acid

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

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

2.3     Stimulation of gut and stomach mucosal morphology

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

Organic acids stimulate cell proliferation

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

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

Organic acids influence villi length and crypt depth in the gut

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

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

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

Organic acids strengthen stomach mucosa

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

2.4    Pigs can use organic acids acid as an energy source

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

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

Acidifiers improve immune response

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

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

In a nutshell

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

By Technical Team, EW Nutrition

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

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

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

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

What makes weaning so stressful for piglets?

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

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

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

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

Weaning support starts before weaning

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

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

Towards a pragmatic stance on creep feed

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

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

Nutritional strategies without antibiotics: focus on pig physiology

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

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

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

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

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

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

Figure 3. Supporting piglets with effective solutions

Crude protein – more of the same?

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

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

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

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

The critical role of digestibility

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

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

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

Amino acids and protein: manage the balance

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

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

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

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

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

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

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

Talking about fiber

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

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

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

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

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

To know more about Gut health products click here.

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

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

In June 2017, the European Commission decided to ban the use of veterinary drugs containing high doses of zinc oxide (3000mg/kg) from 2022. The use of zinc oxide in pig production must then be limited to a maximum level of 150ppm. Companies have been on the lookout for effective alternative strategies to maintain high profitability.

Modern pig production is characterised by its high intensity. In many European countries, piglets are weaned after 3-4 weeks, before their physiological systems are fully developed (e.g. immune and enzyme system). Weaning and thus separation from the mother, as well as a new environment with new germs, means stress for the piglets. Besides, the highly digestible sow’s milk, for which the piglets are wholly adapted, is replaced by solid starter feed.

This, associated with the above-mentioned stressors, can result in reduced feed intake during the first week after weaning and therefore in a delayed adaptation of the intestinal flora to the feed. Since the immune system of animals is not yet fully functional, pathogens such as enterotoxic E. coli can colonize the intestinal mucosa. This can possibly develop into a dangerous dysbiosis, leading to an increased incidence of diarrhea. Inadequate absorption results in suboptimal growth with worse feed conversion. The consequences are economic losses due to higher treatment costs, lower yields, and animal losses.

Diarrhea is one of the most common causes of economic losses in pig production. In the past, this was the reason antibiotics were prophylactically used as growth promoters. Antibiotics reduce antimicrobial pressure and have an anti-inflammatory effect. In addition to reducing the incidence of disease, they eliminate competitors for nutrients in the gut and thus improve feed conversion.

However, the use of antibiotics as growth promoters has been banned in the EU since 2006 due to increased antimicrobial resistance. As a result, zinc oxide (ZnO) appeared on the scene. A study carried out in Spain in 2012 (Moreno, 2012) showed that 57% of piglets received ZnO before weaning and 73% during the growth phase (27-75 days).

Zinc oxide: the disadvantages outweigh the advantages

What made the use of zinc oxide so attractive? Zinc oxide is inexpensive, available in many EU countries, and as a trace element it can be used in high doses through premixing. In some countries, however, a veterinary prescription is needed; in others, the use is already banned.

Zinc is a trace element involved in cell division and differentiation, and it influences the efficacy of enzymes. Since defence cells also need zinc, a supplementation that covers the demand for zinc strengthens the body’s defences. Through a positive effect on the structure of the gut mucosa membrane, zinc protects the body against the penetration of pathogenic germs.

If ZnO is used in pharmacological doses, it has a bactericidal effect against e.g. staphylococci (Ann et al., 2014) and various types of E. coli (Vahjen et al., 2016). Thus, prophylactic use prevents the incidence of diarrhea and the consequent decrease in performance. But the use of zinc oxide also has “side effects”.

Accumulation in the environment

Zinc belongs to the chemical group of heavy metals. For the use as a performance enhancer, it has to be administered in relatively high doses (2000–4000ppm). These high amounts are far above the physiological needs of the animals. With relatively low absorption rates (the bioavailability amounts to approximately 20% (European Commission, 2003)) and subsequent accumulation in manure, zinc can cause substantial contamination of the environment.

Encouraging the development of antibiotic resistance

In addition to the accumulation of zinc in the environment, another aspect also plays an important role: according to Vahjen et al. (2015), a dose of ≥2500mg/kg of food increases the presence of tetracycline and sulfonamide resistance genes in bacteria. In the case of Staphylococcus aureus, the development of resistance to zinc is combined with the development of resistance to methicillin (MRSA; Cavaco et al., 2011; Slifierz et al., 2015). A similar effect can be observed in the development of multiresistant E. coli (Bednorz et al., 2013; Ciesinski et al., 2018).  The reason for this is that the genes that encode antibiotic resistance, i.e. the ones that are “responsible” for the resistance, are found in the same plasmid (a DNA molecule that is small and independent of the bacterial chromosome).

Consequence: no more zinc oxide in the production of piglets from 2022 onwards

The negative effects on the environment and the promotion of antibiotic resistance led to the European Commission’s decision in 2017 to completely ban zinc oxide as a therapeutic agent and as a growth promoter in piglets within five years.

There are effective alternatives to zinc oxide

By the 2022 deadline, the EU pig industry must find a solution to replace ZnO. It must develop strategies that make future pig production efficient, even without substances such as antibiotics and zinc oxide. To this end, measures should be taken at different levels, such as farm management and biosecurity (e.g. effective hygiene management). The promotion of intestinal health for high animal performance is most important, however.

Promotion of gut health through stable gut microbiota

The term eubiosis denotes the balance of microorganisms living in a healthy intestine, which must be maintained to prevent diarrhea and ensure performance. However, weaning, food switching, and other external stressors can endanger this balance. As a result, potentially pathogenic germs can “overgrow” the commensal microbiome and develop dysbiosis. Through the use of functional supplements, intestinal health can be improved.

Phytomolecules – potent compounds created by nature

Phytomolecules, or secondary plant compounds, are substances formed by plants with a wide variety of properties. The best-known groups are probably essential oils, but there are also bitter substances, spicy substances, and other groups.

In animal nutrition, phytomolecules such as carvacrol, cinnamon aldehyde, and capsaicin can help improve intestinal health and digestion. They stabilize the intestinal flora by slowing or stopping the growth of pathogens that can cause disease. How? Phytomolecules, for example, make the cell walls of several bacteria permeable so that cell contents can leak. They also partially interfere with the enzymatic metabolism of the cell or intervene with the transport of ions, reducing the proton motive force. These effects depend on the dose: all these actions can destroy bacteria or at least prevent their proliferation.

Another point of attack for phytomolecules is the communication between microorganisms (quorum sensing). Phytomolecules can prevent microorganisms from releasing substances known as autoinducers, which they need to coordinate joint actions such as the formation of biofilms or the expression of virulence factors.

Medium-chain triglycerides and fatty acids

Medium-chain triglycerides (MCT) and fatty acids (MCFA) are characterised by a length of six to twelve carbon atoms. Thanks to their efficient absorption and metabolism, they can be optimally used as an energy source in piglet feeding. MCTs can be completely absorbed by the epithelial cells of the intestinal mucosa and hydrolysed with microsomal lipases. Hence they serve as an immediately available energy source and can improve the epithelial structure of the intestinal mucosa (Hanczakowska, 2017).

In addition, these supplements have a positive influence on the composition of the intestinal flora. Their ability to penetrate bacteria through semi-permeable membranes and destroy bacterial structures inhibits the development of pathogens such as salmonella and coliforms (Boyen et al., 2008; Hanczakowska, 2017; Zentek et al., 2011). MCFAs and MCTs can also be used very effectively against gram-positive bacteria such as streptococci, staphylococci, and clostridia (Shilling et al., 2013; Zentek et al., 2011).

Prebiotics

Prebiotics are short-chain carbohydrates that are indigestible for the host animal. However, certain beneficial microorganisms such as lactobacilli and bifidobacteria can use these substances as substrates. By selectively stimulating the growth of these bacteria, eubiosis is promoted (Ehrlinger, 2007). In pigs, mannan-oligosaccharides (MOS), fructooligosaccharides (FOS), inulin and lignocellulose are mainly used.

Another element of prebiotics’ positive effect on intestinal health is their ability to agglutinate pathogens. Pathogenic bacteria and MOS can bind to each other through lectin. This agglutination prevents pathogenic bacteria from adhering to the wall of the intestinal mucosa and thus from colonizing the intestine (Oyofo et al., 1989).

Probiotics

Probiotics can be used to regenerate an unbalanced gut flora. To do this, useful bacteria such as bifido or lactic acid bacteria are added to the food. They must settle in the gut and compete with the harmful bacteria.

There are also probiotics which target the communication between pathogens. In an experiment, Kim et al. (2017) found that the addition of probiotics that interfere with quorum sensing can significantly improve the microflora in weaned piglets and thus their intestinal health.

Organic acids

Organic acids show strong antibacterial activity in animals. In their undissociated form, the acids can penetrate bacteria. Inside, the acid molecule breaks down into a proton (H+) and an anion (HCOO-). The proton reduces the pH value in the bacterial cell and the anion interferes with the bacteria’s protein metabolism. As a result, bacterial growth and virulence are inhibited.

Conclusion

Today there are several possibilities in piglet nutrition to effectively support the young animals after weaning. The main objective is to maintain a balanced intestinal flora and therefore to sustain intestinal health – its deterioration often leads to diarrhea and hence to reduced returns. Intestinal health is promoted by stimulating beneficial bacteria and by inhibiting pathogenic ones. This can be achieved through feed additives that have an antibacterial effect and/or support the intestinal mucosa, such as phytomolecules, prebiotics, and medium-chain fatty acids. Through a combination of these possibilities, additive effects can be achieved. Piglets receive optimal support and the use of zinc oxide can be reduced.

References

Ann, Ling Chuo, Shahrom Mahmud, Siti Khadijah Mohd Bakhori, Amna Sirelkhatim, Dasmawati Mohamad, Habsah Hasan, Azman Seeni, and Rosliza Abdul Rahman. “Antibacterial Responses of Zinc Oxide Structures against Staphylococcus Aureus, Pseudomonas Aeruginosa and Streptococcus Pyogenes.” Ceramics International 40, no. 2 (March 2014): 2993–3001. https://doi.org/10.1016/j.ceramint.2013.10.008.

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

Boyen, F., F. Haesebrouck, A. Vanparys, J. Volf, M. Mahu, F. Van Immerseel, I. Rychlik, J. Dewulf, R. Ducatelle, and F. Pasmans. “Coated Fatty Acids Alter Virulence Properties of Salmonella Typhimurium and Decrease Intestinal Colonization of Pigs.” Veterinary Microbiology 132, no. 3-4 (December 10, 2008): 319–27. https://doi.org/10.1016/j.vetmic.2008.05.008.

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 (June 2, 2011): 344–48. https://doi.org/10.1016/j.vetmic.2011.02.014.

Ciesinski, Lisa, Sebastian Guenther, Robert Pieper, Martin Kalisch, Carmen Bednorz, and Lothar H. Wieler. “High Dietary Zinc Feeding Promotes Persistence of Multi-Resistant E. Coli in the Swine Gut.” Plos One 13, no. 1 (January 26, 2018). https://doi.org/10.1371/journal.pone.0191660.

Crespo-Piazuelo, Daniel, Jordi Estellé, Manuel Revilla, Lourdes Criado-Mesas, Yuliaxis Ramayo-Caldas, Cristina Óvilo, Ana I. Fernández, Maria Ballester, and Josep M. Folch. “Characterization of Bacterial Microbiota Compositions along the Intestinal Tract in Pigs and Their Interactions and Functions.” Scientific Reports 8, no. 1 (August 24, 2018). https://doi.org/10.1038/s41598-018-30932-6.

Ehrlinger, Miriam. 2007. “Phytogene Zusatzstoffe in der Tierernährung.“ PhD Diss., LMU München. URN: urn:nbn:de:bvb:19-68242.

European Commission. 2003. “Opinion of the Scientific Committee for Animal Nutrition on the use of zinc in feedingstuffs.”  https://ec.europa.eu/food/sites/food/files/safety/docs/animal-feed_additives_rules_scan-old_report_out120.pdf

Hanczakowska, Ewa. ”The use of medium chain fatty acids in piglet feeding – a review.” Annals of Animal Science 17, no. 4 (October 27, 2017): 967-977. https://doi.org/10.1515/aoas-2016-0099.

Hansche, Bianca Franziska. 2014. „Untersuchung der Effekte von Enterococcus faecium (probiotischer Stamm NCIMB 10415) und Zink auf die angeborene Immunantwort im Schwein. Dr. rer. Nat. Diss., Freie Universität Berlin. https://doi.org/10.17169/refubium-8548

Kim, Jonggun, Jaepil Kim, Younghoon Kim, Sangnam Oh, Minho Song, Jee Hwan Choe, Kwang-Youn Whang, Kwang Hyun Kim, and Sejong Oh. “Influences of Quorum-Quenching Probiotic Bacteria on the Gut Microbial Community and Immune Function in Weaning Pigs.” Animal Science Journal 89, no. 2 (November 20, 2017): 412–22. https://doi.org/10.1111/asj.12954.

Oyofo, Buhari A., John R. Deloach, Donald E. Corrier, James O. Norman, Richard L. Ziprin, and Hilton H. Mollenhauer. “Effect of Carbohydrates on Salmonella Typhimurium Colonization in Broiler Chickens.” Avian Diseases 33, no. 3 (1989): 531–34. https://doi.org/10.2307/1591117.

Shilling, Michael, Laurie Matt, Evelyn Rubin, Mark Paul Visitacion, Nairmeen A. Haller, Scott F. Grey, and Christopher J. Woolverton. “Antimicrobial Effects of Virgin Coconut Oil and Its Medium-Chain Fatty Acids On Clostridium Difficile.” Journal of Medicinal Food 16, no. 12 (December 2013): 1079–85. https://doi.org/10.1089/jmf.2012.0303.

Slifierz, M. J., R. Friendship, and J. S. Weese. “Zinc Oxide Therapy Increases Prevalence and Persistence of Methicillin-Resistant Staphylococcus Aureus in Pigs: A Randomized Controlled Trial.” Zoonoses and Public Health 62, no. 4 (September 11, 2014): 301–8. https://doi.org/10.1111/zph.12150.

Vahjen, Wilfried, Dominika Pietruszyńska, Ingo C. Starke, and Jürgen Zentek. “High dietary zinc supplementation increases the occurrence of tetracycline and sulfonamide resistance genes in the intestine of weaned pigs.” Gut Pathogens 7, article number 23 (August 26, 2015). https://doi.org/10.1186/s13099-015-0071-3.

Vahjen, Wilfried, Agathe Roméo, and Jürgen Zentek. “Impact of zinc oxide on the immediate postweaning colonization of enterobacteria in pigs.” Journal of Animal Science 94, supplement 3 (September 1, 2016): 359-363. https://doi.org/10.2527/jas.2015-9795.

Zentek, J., S. Buchheit-Renko, F. Ferrara, W. Vahjen, A.G. Van Kessel, and R. Pieper. “Nutritional and physiological role of medium-chain triglycerides and medium-chain fatty acids in piglets” Animal Health Research Reviews 12, no. 1 (June 2011): 83-93. https://doi.org/10.1017/s1466252311000089.

Antimicrobial resistance is a natural process but this is accelerated by inappropriate prescribing of antimicrobials, poor infection control practices and the unnecessary use of antimicrobials in agriculture (Barber and Sutherland, 2017).

Antimicrobial resistance – a threat to humanity

Resistance to specific antibiotics occurs through mutations that enable the bacteria to withstand an antibiotic treatment. One mechanism is the production of enzymes degrading or altering the antibiotic, rendering them harmless. The elimination of entrances for antibiotics or the development of pumps discharging them is another possibility. A further option is the elimination of the targets the antibiotic would attack.

So-called “resistance genes” are responsible for resistance. These genes can be transferred from one bacterium to another and also from beneficial bacteria to harmful ones. When antibiotics are used, “normal” bacteria are killed; the resistant ones survive and have all possibilities to proliferate. The Dutch Government has been tracking resistant bacteria in poultry flocks for the last two decades. A clear correlation between antibiotic use and the percentage of resistance could be observed. The good thing: according to the 2020 MARAN report (De Greeff et al., 2020), by reducing the use of antibiotics, the occurrence of resistances can be pushed back.

Figure 1. Sales of antibiotics from 1999 to 2016 and the development of resistances (MARAN report, 2018)

Antibiotic use in animal production

In pig production, antibiotics are often used in stressful situations such as weaning or moving. Antibiotics decrease the pathogenic pressure in animals and help them overcome these critical periods. Disadvantage: Antibiotics do not differentiate between good and bad but between susceptible and resistant. Therefore, also the beneficial gut flora gets destroyed through antibiotic treatment, and resistance is spread.

After the ban of antibiotic growth promoters in Europe in 2006, the US has also made considerable efforts to reduce the use of antibiotics.

Is performance at risk without antibiotics?

When antibiotics are taken out of livestock production, measures in different areas must be implemented to keep performance and profitability high. Without supporting the animals by other means, they will get sick and even die in acute cases. Subclinical disease forms reduce their feed intake, and growth performance consequently decreases. According to literature, losses due to decreased average weight gain can be up to $40 per pig (Hao et al., 2014).

Goal: reducing antibiotics while maintaining performance

To support pigs, especially during the afore-mentioned critical periods, alternatives focusing on the maintenance of gut health and, therefore, also overall health must be chosen. This goal can only be achieved by balancing the intestinal flora with reducing pathogenic bacteria occurrence.

Phytomolecules are an effective solution

Phytomolecules are produced by plants to defend themselves against predators or pathogens. Farmers use the substances in animal feeds to support digestion, improve palatability, but also to reduce pathogenic pressure (Baser and Buchbauer, 2010).

In animal feeding, different application forms are available:

• As premixes containing microencapsulated phytomolecules with a slow release. This version is mixed into the feed in the feed mill and constitutes continuous long-term support for the animals. Due to microencapsulation, the active substances are released where they are needed – in the gut.
• As liquid complementary feeds for the application via the waterline. The application of the liquid form to the animals can be decided from one day to the other. It is an optimal additional tool to support the pigs in challenging situations such as weaning.

Scientific trials show: In-feed phytomolecules support performance

A trial conducted at the Federal University of Lavras (Brazil) evaluated if phytomolecules as a regular diet component can deliver the same effects on growth performance as AGPs in pig production.

For the trial, 108 castrated newborn male pigs were allocated to 3 groups (control, AGP (antibiotic growth promoters), and Activo). Pigs were weaned at 23 days of age with an average weight of 6.3 kg. They were fed a 3-phase diet (nursery, growing, and finishing). The inclusion rates of the additives (antibiotics and phytomolecules-based product – Activo) are shown in table 1.

On days 0, 1, and 2 of the experiment, the animals were challenged by applying a solution containing 10⁷ CFU of E. coli K88, producing the toxins LT, Sta, and bST. Additionally, during the two last days before the growing phase, the animals were exposed to 5h of heat stress, using infrared lamps and closed windows. The parameters weight gain, final weight, FCR, and gut flora composition in the cecum were evaluated.

Table 1. Inclusion rate of the additives in the feed
AGP: Antibiotic growth promoter; Activo: product based on phytomolecules, microencapsulated (EW Nutrition)

Results

The results of this trial are shown in figure 2.

Concerning growth performance, the group fed the phytomolecules-based product Activo showed a 4.36 kg higher final weight after 126 days than the group provided AGPs (p=0.11), resulting in a 3.28 kg higher weight gain (p=0.21) and a 13 points better feed conversion.

Figure 2. Data of growth performance including final weight, weight gain and FCR adjusted to 100kg

The evaluation of some bacteria naturally occurring in the gut flora showed that, in contrast to the antibiotic prophylaxes, Activo has no negative impact on E. coli, Lactobacillus and Bifidobacterium. However, the antibiotic group showed a slight decrease in the population of Lactobacilli (Figure 3).

Figure 3. Impact of antibiotics and phytomolecules (Activo) on the composition of the gut flora

This trial shows Activo increasing growth performance and feed conversion without any negative impact on gut flora. The addition of phytomolecules (Activo) to the feed is documented as optimal long-term support instead of antibiotic growth promoters.

Trial shows: Phytomolecules support animals in critical situations like weaning

In a trial conducted in the USA, a product containing phytomolecules and organic acids (Activo Liquid, EW Nutrition) was compared to an antibiotic for controlling bacterial diseases in US pig production (Mecadox). For the trial, a total of 360 weanling pigs, about 19 days old and weighing 5.70 kg, were divided into four groups. Each group consists of 9 pens with 10 animals per pen. All groups were fed a 3-phase diet.

To the different trial groups, the following products were added (table 2):

These performance parameters were evaluated: live weight, daily gain, daily feed intake, feed:gain ratios, and mortality.

Table 2. Feeding and inclusion of the additives

Results

The results of the trial are shown in figure 4. Concerning growth, no significant differences could be seen between the groups, only numerical differences. Live weight in the antibiotic group was 25.95 kg, and in the Activo Liquid groups, it ranges from 25.77 kg (shortest period of application) to 26.20 kg (see below). This resulted in calculated values for an average daily gain of 473 g in the Mecadox fed animals and 463 to 487g in the Activo Liquid groups. Due to a lower feed intake per kg of weight gain, all groups fed Activo Liquid showed a significantly (p=0.05) better feed conversion than the Mecadox group.

Figure 4. Live weight in the groups fed the antibiotic Mecadox and the phytomolecules-based product Activo Liquid for different periods
Average daily gain in the different trial groups
Average daily feed intake in the different trial groups (P=0.05)

Concerning mortality, the group fed Activo Liquid for 5 days showed the lowest mortality rate of 1.1% (figure 5).

Figure 5. Feed:gain ratio in the different trial groups (P=0.05) & Mortality rates

Considering all parameters, the group fed Activo Liquid for five days provided the best results: numerically the lowest mortality rate, highest daily gain, and one of the two lowest feed:gain ratios. This trial concludes that Activo Liquid with an application period of five days can safely replace antibiotic growth promoters in the diet. Therefore, Activo Liquid is an interesting tool to additionally support pigs during critical periods of life.

Phytomolecules help keep health and performance together

The trials conducted with two types of phytomolecules-based products show that phytomolecules efficiently support pigs to achieve their genetic potential. A basic supply of these substances within the feed yields results similar to those of animals receiving antibiotic growth promoters (AGPs). In challenging situations like weaning, additional short-term supply is recommended, which can be done with liquid products via the waterline.

With this strategy, the use of antibiotic growth promoters and, therefore, antibiotics in general can be drastically reduced. This approach can help decrease antimicrobial resistance and, not to be forgotten, accommodates final customers’ requests for the lower usage of antibiotics in livestock.

References

Barber, Sarah, and Nikki Sutherland. “O’Neill Review into Antibiotic Resistance.” House of Commons Library, March 6, 2017. https://commonslibrary.parliament.uk/research-briefings/cdp-2017-0074/.

Baser, Kemal Hüsnü Can, and Gerhard Buchbauer. Handbook of Essential Oils: Science, Technology, and Applications. Boca Raton, FL: Taylor & Francis distributor, 2010.

Davies, Dame Sally. “Antibiotic Resistance ‘Big Threat to Health’.” BBC News. BBC, November 16, 2012. https://www.bbc.co.uk/news/health-20354536.

De Greeff, S.C., A.F. Schoffelen, and C.M. Verduin. “MARAN Reports.” WUR. National Institute for Public Health and the Environment – Ministery of Health, Welfare and Sport, June 2020. https://www.wur.nl/en/Research-Results/Research-Institutes/Bioveterinary-Research/In-the-spotlight/Antibiotic-resistance/MARAN-reports.htm.

Hao, Haihong, Guyue Cheng, Zahid Iqbal, Xiaohui Ai, Hafiz I. Hussain, Lingli Huang, Menghong Dai, Yulian Wang, Zhenli Liu, and Zonghui Yuan. “Benefits and Risks of Antimicrobial Use in Food-Producing Animals.” Frontiers in Microbiology 5, no. Art. 288 (2014): 1–11. https://doi.org/10.3389/fmicb.2014.00288.

Marquardt, Ronald R, and Suzhen Li. “Antimicrobial Resistance in Livestock: Advances and Alternatives to Antibiotics.” Animal Frontiers 8, no. 2 (2018): 30–37. https://doi.org/10.1093/af/vfy001.

O’Neill, J. “Tackling Drug-Resistant Infections Globally.” Review on Antimicrobial Resistance. Wellcome Trust / HM Government, May 19, 2016. https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf.

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