Author: Ajay Bhoyar, Senior Global Technical Manager, EW Nutrition

The global use of feed enzymes has become a central feature of efficient monogastric animal production systems. Rising feed ingredient costs, tighter margins, and increasing regulatory pressure to reduce environmental impact have all accelerated enzyme innovation. At the same time, feed mills have shifted toward higher conditioning temperatures and time in pursuit of improved pellet durability, pathogen control, and throughput. However, this creates a hostile environment for most exogenous feed enzymes, which can lose significant activity under the harsh conditions of feed processing.

Historically, enzyme manufacturers have attempted to overcome heat degradation of by coating, encapsulating, or post-pelleting liquid application (PPLA) of enzymes. While these approaches provide partial solutions, they can also have limitations, including delayed enzyme activity, uneven distribution, reduced mixing uniformity, and reliance on specialized liquid enzyme applicators.

These limitations prompted a novel direction: enzymes designed or selected to be intrinsically heat-stable, capable of surviving pelleting without protective matrices.

This article highlights recent advancements in intrinsically heat-stable xylanase technology, explains its advantages over coated and post-pelleting enzyme solutions, and outlines its practical benefits for feed manufacturers, integrators, and nutritionists operating under modern high-temperature feed pelleting conditions.

Intrinsically Thermostable Enzymes

An enzyme is considered intrinsically heat-stable when its native protein structure resists unfolding and retains catalytic activity under high temperatures associated with feed processing—typically 80–95°C for 30–90 seconds. Unlike coated enzymes that rely on external protection, intrinsically thermostable enzymes depend on their internal protein architecture for heat tolerance. Enzymes from organisms living in compost, thermal springs, and geothermal soils naturally withstand temperatures of 80–100 °C or higher. Intrinsically thermostable enzymes are often sourced from thermophiles (organisms living in hot springs and deep-sea vents) or engineered for stability. They resist denaturation (loss of shape and function) at high-temperature processing.

Storage and transport stability

Reduces the need for over-formulation or overdosing of the enzyme

Better mixing uniformity in the feed, as coating is not required

Superior and consistent post-pelleting recovery across different feed mills

Lower cost-in-use due to reliable, repeatable enzyme performance

Consistently better animal performance

Limitations of Current Thermostability Solutions

Coating / Encapsulation

A method of protecting enzymes from heat is to encapsulate or coat them with a protective coating. An ideal enzyme coating for animal feed needs to:

1. Protect the enzyme through steam conditioning (typically 85–90°C or higher) and through subsequent pelleting.

2. Release the enzyme from the coating quickly in the gastrointestinal tract of the target animal, to ensure optimum efficacy. (Gilbert and Cooney, 2007)

There is some evidence, however, suggesting that the coating of enzymes may reduce the efficacy of the product, compared to an uncoated version of the same product (Kwakkel et al., 2000).

Post-Pelleting Liquid Application (PPLA)

Post-pelleting liquid enzyme application requires sophisticated applicators to minimize the risk of uneven spraying or calibration errors, which is often not feasible in small or mid-size mills. Accurate application of the liquid enzyme, as with some other critical liquid micro-ingredients, requires specialized spraying equipment and, even then, consistency of accurate enzyme application can be an issue (Bedford and Cowieson, 2009). Research has shown that as much as 30% of the enzyme activity can be found in the pellet fines, and therefore, adding the enzyme before screening would result in a lower than expected dosage in the final feed and wastage of the enzyme product (Engelen, 1998). In some cases, adjusting the pelleting machines to the output of the PPLA’s spray nozzles to ensure a homogenous and even application of the enzyme on the pellets may reduce the overall pellet production rate, especially in big feed mills with very high throughput.

These limitations of the coated or PPLA technologies strengthen the value proposition of intrinsically heat-stable enzymes.

Nutritional and Commercial Benefits of Intrinsically Heat-Stable Xylanase

The use of intrinsically heat-stable xylanase delivers consistent nutritional benefits in poultry and swine feeds, including predictable non-starch polysaccharide (NSP) degradation, a significant increase in the metabolizable energy (ME) value of the feed, and enhanced gut health resilience supporting reduced antibiotic use.

From a commercial and operational perspective, this technology simplifies enzyme application, improves mixing uniformity, reduces formulation risk, and lowers feed cost per unit of meat or egg produced.

In-Vitro Thermal Stability Profile of Axxess XY

Axxess XY is a novel, intrinsically thermostable GH10 xylanase originating from Thermotoga maritima, a hyperthermophilic bacterium found in hydrothermal vents near volcanic grounds, and commercially it is produced by proprietary strain of Bacillus subtilis.

The superior heat stability of Axxess XY has been proven under various commercial pelleting conditions across different geographies. Axxess XY showed excellent post-pelleting recovery under commercial feed-milling conditions across varying temperatures and conditioning times (Fig. 2).

In one study, in addition to excellent post-pelleting recovery, Axxess XY also demonstrated high xylanase stability in pelleted feed over a 2-month feed storage period at>40°C, with humidity around 65%.

Conclusions

As feed mills continue to operate at higher conditioning temperatures and longer retention times, enzyme heat stability has become a critical success factor in modern feed production. Intrinsically heat-stable xylanase offers a practical and reliable solution to this challenge by maintaining enzyme activity through pelleting without the need for coatings or post-pelleting liquid application systems.

By relying on its native protein structure rather than external protection, intrinsically thermostable xylanase delivers consistent post-pelleting recovery, uniform distribution in feed, and predictable nutritional performance across different feed mills and processing conditions. This reliability translates into improved nutrient utilization, better gut health support, and reduced cost per kilogram of meat or eggs produced.

From an operational standpoint, intrinsically heat-stable xylanase simplifies enzyme application, reduces dependence on specialized equipment, and minimizes the need for over-formulation or safety margins. These advantages help feed manufacturers and integrators improve efficiency, lower risk, and achieve more consistent results, especially under demanding commercial pelleting conditions.

In summary, intrinsically heat-stable xylanase aligns well with the evolving needs of today’s feed industry, offering a robust, cost-effective, and future-ready enzyme solution for high-performance animal production systems.

References:

Bedford, M. R., and A. J. Cowieson. 2009. “Phytate and Phytase Interactions.” In Proceedings of the 17th European Symposium on Poultry Nutrition, 7–13. Edinburgh, UK.

Eeckhout, M., M. De Schrijver, and E. Vanderbeke. 1995. “The Influence of Process Parameters on the Stability of Feed Enzymes during Steam Pelleting.” In Proceedings of the 2nd European Symposium on Feed Enzymes, 163–169. Noordwijkerhout, The Netherlands.

Engelen, G. M. A. 1998. Technology of Liquid Additives in Post-Pelleting Applications. Wageningen, The Netherlands: Wageningen Institute of Animal Science.

Gilbert, T. C., and G. Cooney. 2011. “Thermostability of Feed Enzymes and Their Practical Application in the Feed Mill.” In Enzymes in Farm Animal Nutrition, 2nd ed., edited by M. R. Bedford and G. G. Partridge, 249–259. Wallingford, UK: CABI.

Kwakkel, R. P., P. L. van der Togt, and K. A. B. M. Holkenborg. 2000. “Bio-Efficacy of Two Phytase Formulations Supplemented to a Corn–Soybean Broiler Diet.” In Proceedings of the 3rd European Symposium on Feed Enzymes, 63–64. Noordwijkerhout, The Netherlands.

By Ilinca Anghelescu, Dr. Andreas Michels, Predrag Persak

Our understanding of how nutrition influences growth and resilience in poultry has greatly expanded in recent years. It is now clear that animal performance stems to a large extent from a balance between metabolism, immune function, and the gut microbiome. These systems interact continuously, and even small nutritional or environmental changes can shift the animals’ physiological response. This growing knowledge has encouraged the development of nutritional strategies and feed components that work through adaptive, non-antibiotic mechanisms. One recent proposed explanation for these responses has rapidly gained ground: hormetic modeling.

Hormetic modeling describes how small or moderate doses of nutritional components can activate beneficial adaptive responses (improved resilience or metabolic efficiency), while excessive doses become harmful. This idea parallels, largely speaking, Paracelsus’s famous principle: “The dose makes the poison.” In poultry nutrition, such hormetic patterns are well recognized in nutrients like trace elements (selenium, zinc) and specific amino acids (for example, arginine). At optimal levels, these nutrients support antioxidant defense, growth, and immune balance, whereas excessive intake may cause oxidative or metabolic stress

This review examines the hormetic principle and its application to modern poultry/swine feeding concepts, exploring how balanced nutrient design and controlled inclusion of bioactive compounds can strengthen cellular adaptation, improve stress tolerance, and enhance production efficiency.

How do AGPs actually work?

Despite AGP’s widespread historical use, the precise mechanisms by which subtherapeutic doses of antibiotics enhance animal productivity remained poorly understood. Recent advances in systems biology and mitochondrial research propose new answers, much needed to develop future advanced nutritional systems.

The traditional explanations for AGP efficacy have focused primarily on antimicrobial effects:

• reducing nutrient competition from microorganisms
• decreasing harmful bacterial metabolites
• improving gut wall morphology (thinner gut wall ➡ better nutrient absorption)
• preventing subclinical infections

However, these mechanisms alone could not fully explain why different classes of antibiotics with diverse mechanisms of action produce similar growth-promoting effects (Gutierrez-Chavez et al., 2025).

Niewold (2007) hypothesized that the primary mechanism of AGPs is non-antibiotic anti-inflammatory activity, reducing the energetic costs of chronic low-grade inflammation. Inflammation diverts nutrients from growth toward immune responses, with cytokine production (particularly IL-1β, IL-6, and TNF-α) suppressing anabolic pathways (Kogut et al., 2018). AGPs appear to selectively inhibit pro-inflammatory cytokine production without completely suppressing immune function.

A paper published in 2024 by Fernandez Miyakawa et al. proposes that antibiotics at subtherapeutic levels act primarily through mitochondrial hormesis and adaptive stress responses, and not simply through antimicrobial activity. In this model, mitochondria act as bioenergetic hubs and signaling centers. Low-dose antibiotics trigger mild mitochondrial stress, which triggers the activation of adaptive protective pathways.  This in turn induces mitokine release, leading to systemic adaptive responses improving growth, feed efficiency, and disease tolerance.

Mechanism of action in the hormetic model of AGP efficiency

Hormesis is a biphasic mechanism whereby high doses are toxic, but low doses stimulate adaptive responses and are beneficial. In the case of AGPs, Fernandez Miyakawa et al. propose that low doses stimulate growth, stress resistance, and cellular repair.

Key signaling pathways

As Bottje et al. (2006, 2009) shows, efficient animals often have mitochondrial inner membranes that are less permeable to protons and other ions, allowing for more effective coupling between electron transport and ATP synthesis, which reduces energy loss through proton leak and maximizes the production of ATP per oxygen molecule consumed. Lower membrane permeability is influenced by factors like decreased membrane surface area per protein mass, specific membrane protein content (such as adenine nucleotide translocase), and fatty acid composition in the membrane phospholipids, all contributing to a tighter barrier that prevents unregulated electron or proton flow and supports higher energetic efficiency. Such features make mitochondria in efficient species more capable of maintaining membrane integrity and ATP generation, especially when facing environmental stress, as seen in freeze-tolerant animals whose mitochondria do not undergo damaging permeability transitions under extreme conditions.

Nrf2

Many AGPs interfere with mitochondrial protein synthesis and electron transport chain. At subtherapeutic levels, they cause a mild ROS increase, which triggers the activation of redox-sensitive transcription factor Nrf2. Since Nrf2 regulates over 250 antioxidant, detoxification, and anti-inflammatory genes, the result is improved cell survival, redox balance, and tolerance to stress.

Mitokine production

Mitokines are “signaling molecules that enable communication of local mitochondrial stress to other mitochondria in distant cells and tissues” (Burtscher 2023). Through fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), adrenomedullin2 (ADM2) etc, these stress signals are released systemically and coordinate tissue-wide responses, leading to improved growth and resilience.

Inflammation and disease defense

While the negative side of antibiotic growth promoters is well researched and understood (Rahman et al., 2022), science can advance by isolating the positive effects and attempting to offer different pathways to the same benefits. One such lesson can be derived from understanding inflammation pathways and responses.

Chronic low-grade intestinal inflammation is common in modern poultry production, due to diet, microbiota shifts, high metabolic demands etc. This inflammation diverts energy from growth to immune responses.

AGPs reduce the energy costs of this inflammation in three main ways:

• Reduces inflammation through adaptive stress response
• Raising the threshold to trigger inflammation
• Promoting overall resilience, rather than simply killing pathogens

Fernandez Miyakawa et al. suggest, in this emerging model, that disease defense can operate two different actions: resistance to health challenges through reduction of the pathogen load (which is driven by the immune system and is energy costly); and overall resilience by reducing host damage without reducing the pathogen load. AGPs, the authors claim, mainly promote resilience by enhancing mitochondrial stress responses and tissue repair, i.e. more precisely:

• Direct mitochondrial stimulation in intestinal epithelial cells
• Systemic mitokine signaling coordinating organism-wide adaptive responses
• Selective microbiota modulation enhancing beneficial host-microbe interactions
• Improving resilience without immune system costs
• Metabolic optimization supporting growth and feed efficiency

In this context, “metabolic optimization” refers to the enhancement of metabolic processes within livestock or poultry to support efficient growth, feed conversion, and physiological resilience, without relying on immune-mediated pathways that are energetically costly. Scientific evidence shows that metabolic optimization involves improving nutrient assimilation, promoting more efficient energy production in tissues (such as mitochondrial ATP synthesis), and minimizing wasteful metabolic byproducts, resulting in reduced feed intake per unit of growth and better utilization of dietary nutrients (Rauw 2025, El-Hack 2025).

Function of feed additives and feed components

Feed additives and feed components in many ways represent the complete other side of the spectrum from antibiotics, but are there some features where antibiotics and feed additives come close in their functions? There is a good case to be made for certain feed additives ultimately working in the animal to achieve similar benefits to the desirable, non-medicinal usage of AGP´s. Especially with the emergent model of AGP mechanism described above, it is worth discussing how certain feed additives can support the same end goal: promoting animal resilience.

Lillejhoj et al (2018), Gutierrez-Chavez et al. (2025) and others outline the end-results such products must achieve:

• Growth performance & feed conversion efficiency
• Promotion of animal productivity under real-world conditions
• Support gut homeostasis
• Non-adverse effect on the immune system
• Reduction of oxidative stress
• Support organism in mitigation of enteric inflammatory consequences

Within the hormetic model, possibly the most important systemic benefit is, in one phrase, promoting resilience. Phytomolecules have long been used, in human and animal medicine, for the same end goal. The mechanisms described below should naturally be seen with caution, as phytomolecule microbiome effects can be subtler and context-dependent. However, the substantiating literature has been increasingly accumulating on these specific topics.

1. Immunometabolic regulation

Phytomolecules demonstrate remarkably similar anti-inflammatory effects to what Niewold (2007) suggested was a primary mechanism of AGPs: non-antibiotic anti-inflammatory activity, reducing the energetic costs of chronic low-grade inflammation. Inflammation diverts nutrients from growth toward immune responses, with cytokine production (particularly IL-1β, IL-6, and TNF-α) suppressing anabolic pathways (Kogut et al., 2018). AGPs appear to selectively inhibit pro-inflammatory cytokine production without completely suppressing immune function. A similar effect can be observed with various types of phytomolecules, which significantly reduced pro-inflammatory and/or increased anti-inflammatory cytokine expression in animals challenged with several pathogens. The anti-inflammatory mechanism appears to involve inhibition of NF-κB activation and modulation of MAPK signaling pathways (Kim et al., 2010; Long et al., 2021).

2. Mitochondrial hormesis and energy metabolism

Fernández Miyakawa et al. (2024, see above) proposed that AGPs exert growth-promoting effects through mitochondrial hormesis – subtherapeutic antibiotic doses induce mild mitochondrial stress, triggering adaptive responses that enhance mitochondrial function, energy metabolism, and cellular resilience. This mechanism, while requiring further validation, explains why different antibiotics with diverse targets produce similar growth outcomes.

The mitochondrial stress response involves activation of the IL-6 receptor family signaling cascade, which regulates metabolism, growth, regeneration, and homeostasis in liver and other tissues (Perry et al., 2024). Subtherapeutic antibiotic exposure activates proteins involved in growth and proliferation through IL-6R gp130 subunit signaling, including JAK, STAT, mTOR, and MAPK pathways.

Phytomolecules demonstrate similar mitochondrial effects. Perry et al. (2024) showed that increased activity of AMPK, mTOR, PGC-1α, PTEN, HIF, and S6K can also be available via phytomolecule activity, suggesting enhanced anabolic metabolism.

Capsicum oleoresin supplementation in broilers increased jejunal lipase and trypsin activity, enhanced ileal amylase activity, improved jejunal morphology, and modulated immune organ development, indicating enhanced digestive efficiency and nutrient utilization (Li et al., 2022).

Compounds such as vanillin, thymol, eugenol have been shown to improve glucose and lipid metabolism through TRPV1 activation and mitochondrial function enhancement (Gupta et al., 2022; Zhang et al., 2017).

3. Gut microbiota modulation

AGPs selectively reduce specific microbial populations, particularly Lactobacillus species that produce bile salt hydrolase (BSH). Since BSH reduces fat digestibility and thus weight gain, AGP-mediated reduction of BSH-producing bacteria enhances energy extraction and growth (Lin, 2014; Bourgin et al., 2021).

Recent research by Zhan et al. (2025) using single-molecule real-time 16S rRNA sequencing demonstrated that therapeutic antibiotic doses (lincomycin, gentamicin, florfenicol, benzylpenicillin, ceftiofur, enrofloxacin) significantly altered chicken gut microbiota composition, with Pseudomonadota and Bacillota becoming dominant phyla after exposure. Different antibiotics produced distinct temporal effects on microbial diversity and community structure.

Phytomolecules exert targeted antimicrobial effects while promoting beneficial bacteria. Dietary supplementation with 800 mg/kg Capsicum extract in Japanese quails reduced cecal counts of pathogenic bacteria (Salmonella spp., E. coli, coliforms) while modulating Lactobacilli populations (Reda et al., 2020).

In pigs, 80 mg/kg natural capsicum extract increased cecal propionic acid and total volatile fatty acid concentrations, with increased butyric acid in the colon – indicating enhanced fermentation by beneficial bacteria (Long et al., 2021).

Capsicum and Curcuma oleoresins altered intestinal microbiota composition in commercial broilers challenged with necrotic enteritis, reducing disease severity through microbiome modulation (Kim et al., 2015).

Capsaicin demonstrates selective antimicrobial activity, inhibiting pathogenic Gram-negative bacteria while favoring development of certain Gram-positive bacteria. The antibacterial mechanism involves induction of osmotic stress and membrane structure damage (Adaszek et al., 2019; Rosca et al., 2020).

4. Intestinal barrier function and gut health

AGPs have been associated with improved intestinal morphology, including increased villus height and reduced crypt depth, which enhance absorptive capacity (Gaskins et al., 2002).

Phytomolecules produce similar or superior effects. Capsicum extract (80 mg/kg) in pigs increased ileal villus height and upregulated MUC-2 gene expression, indicating enhanced gut barrier function and integrity. The improved barrier function correlated with reduced diarrhea incidence (Liu et al., 2013; Long et al., 2021).

Allium hookeri extract increased expression of tight junction proteins (claudins, occludins, ZO-1) in LPS-challenged broiler chickens, demonstrating direct enhancement of barrier integrity (Lee et al., 2017).

5. Oxidative stress mitigation

Oxidative stress impairs growth by damaging cellular components and triggering inflammatory responses. AGPs reduce oxidative stress indirectly through anti-inflammatory effects and microbiota modulation (Bortoluzzi et al., 2021).

Phytomolecules possess direct antioxidant properties. Capsicum extract (50 mg/kg) in heat-stressed quails reduced serum and ovarian malondialdehyde (MDA) while increasing superoxide dismutase (SOD) and catalase (CAT) activities. Ovarian transcription factors showed decreased NF-κB and increased Nrf2 and HO-1 expression (Sahin et al., 2016).

A mixture of herbal extracts including pepper reduced thiobarbituric acid reactive substances and MDA in broiler liver and muscle, while increasing glutathione peroxidase (GSH-Px) activity and improving antioxidant enzyme expression (Saleh et al., 2018).

Capsicum extract (80 mg/kg) in pigs increased total antioxidant capacity, SOD, and CAT while reducing MDA levels, demonstrating robust antioxidant effects (Long et al., 2021).

Standardization and controlled release: Critical success factors

A major criticism of phytomolecules has been inconsistent efficacy across studies. However, this variability largely reflects differences in:

• Active compound concentrations
• Bioavailability and stability
• Dosing precision
• Product quality and standardization

Microencapsulation is one of the technologies that address the standardization and bioavailability challenges. It protects volatile compounds from degradation during feed processing and storage, with encapsulated essential oils showing significantly higher retention compared to unprotected forms (Stevanović et al., 2018). By creating a protective barrier around active ingredients, microencapsulation enables controlled release in specific regions of the gastrointestinal tract, improving absorption efficiency and reducing dose variability (Bringas-Lantigua et al., 2011). The technology also masks unpalatable flavors that can reduce feed intake while standardizing active ingredient concentrations through precise manufacturing processes (Gharsallaoui et al., 2007). Studies demonstrate that spray-dried microencapsulated essential oils achieve encapsulation efficiencies exceeding 93% with minimal loss during storage (Hu et al., 2020), and can be engineered for enzyme-mediated release to ensure bioactive delivery at optimal intestinal sites (Elolimy et al., 2025).

Mechanistic synthesis: An integrated model

The evidence indicates that both AGPs and phytomolecules operate through an integrated network of effects:

1. Primary Level: Selective antimicrobial effects modify gut microbiota composition
2. Secondary Level: Reduced microbial metabolites (ammonia, endotoxins) decrease inflammatory signaling
3. Tertiary Level: Reduced inflammation conserves energy for growth; enhanced barrier function improves nutrient absorption
4. Quaternary Level: Mitochondrial hormesis and metabolic optimization increase energy efficiency
5. Systemic Level: Improved immunometabolic homeostasis supports optimal growth

This integrative model explains why multiple antibiotics with different mechanisms produce similar growth outcomes: they converge on common pathways regulating immunometabolism and mitochondrial function (Fernández Miyakawa et al., 2024).

Phytomolecules operate through the same mechanistic framework but with potential advantages:

• Multiple bioactive compounds providing redundancy
• Antioxidant effects enhancing stress resilience
• Lower AMR selection pressure
• Potential prebiotic-like effects supporting beneficial microbiota

Safety and antimicrobial resistance considerations

Antibiotic exposure significantly disrupts gut microbiota diversity and stability, with effects persisting beyond withdrawal periods. The study by Zhan et al. (2025) demonstrated that different antibiotics produce varying degrees of microbiota disruption, with florfenicol and gentamicin showing the strongest and most persistent effects.

In contrast, phytomolecules generally do not generate resistance through the same mechanisms as antibiotics. Some phytochemicals may actually enhance antibiotic efficacy and resensitize resistant bacteria through structural modifications of bacterial membranes (Khameneh et al., 2021; Suganya et al., 2022).

However, one study reported increased correlation between antibiotic resistance genes (ARGs) and mobile genetic elements in pig feces after mushroom powder supplementation, suggesting that certain phytogenic compounds may increase ARG mobility (Muurinen et al., 2021). This emphasizes the need for continued surveillance of phytomolecule effects on resistance gene dynamics.

Capsaicinoids and capsinoids have well-established safety profiles. Capsiate, a non-pungent analogue of capsaicin, exhibits substantially lower toxicity while maintaining similar metabolic and growth-promoting effects (Gupta et al., 2022). No adverse effects on animal health or product quality have been reported at recommended dosages in reviewed studies.

Future directions and research needs

Despite substantial progress, several areas require further investigation:

1. Mechanistic refinement: Detailed characterization of signaling pathways, particularly the IL-6R/gp130 cascade and mitochondrial stress responses
2. Precision formulation: Development of combinations optimized for specific production stages, environmental conditions, and disease pressures
3. Bioavailability optimization: Advanced delivery systems ensuring consistent active compound release and absorption
4. Microbiome-host interaction mapping: High-resolution characterization of microbial community shifts and their functional consequences
5. Economic validation: Large-scale production trials assessing cost-effectiveness compared to AGPs and disease management costs

Conclusions

The scientific evidence demonstrates that standardized phytomolecules operate through well-characterized biological mechanisms that substantially replicate those of AGPs:

1. Anti-inflammatory effects reducing energetic costs of immune activation
2. Mitochondrial hormesis enhancing energy metabolism and cellular resilience
3. Selective microbiota modulation supporting beneficial bacteria while controlling pathogens
4. Intestinal barrier enhancement improving nutrient absorption and reducing translocation
5. Antioxidant activity mitigating oxidative stress and supporting immune function

When properly standardized and formulated for controlled release, phytomolecules deliver growth promotion, feed efficiency improvements, and disease resistance comparable to AGPs, while potentially offering advantages in AMR risk profile, stress resilience, and consumer acceptance.

The mechanistic convergence between AGPs and phytomolecules, coupled with demonstrated efficacy in controlled trials, provides producers with confidence that science-based phytomolecular interventions represent legitimate alternatives to AGPs. Success depends on product standardization, appropriate dosing, and understanding that phytomolecules work through fundamental biological pathways rather than undefined or mystical mechanisms.

As the livestock industry continues to navigate the post-AGP era, standardized phytomolecules offer a scientifically sound, mechanistically validated approach to maintaining animal performance, health, and welfare while addressing antimicrobial resistance concerns.

References

Adaszek, Ł., et al. “Properties of Capsaicin and Its Utility in Veterinary and Human Medicine.” Research in Veterinary Science, vol. 123, 2019, pp. 14 – 19.

Bottje, W., et al. “Mitochondrial proton leak kinetics and relationship with feed efficiency within a single genetic line of male broilers”. Poultry Science, Volume 88, Issue 8, 1 August 2009, p. 1683-1693.

Bortoluzzi, C., et al. “A Protected Complex of Biofactors and Antioxidants Improved Growth Performance and Modulated the Immunometabolic Phenotype of Broiler Chickens Undergoing Early Life Stress.” Poultry Science, vol. 100, 2021, p. 101176.

Bourgin, M., et al. “Bile Salt Hydrolases: At the Crossroads of Microbiota and Human Health.” Microorganisms, vol. 9, no. 1122, 2021.

Bravo, D., et al. “A Mixture of Carvacrol, Cinnamaldehyde, and Capsicum Oleoresin Improves Energy Utilization and Growth Performance of Broiler Chickens Fed Maize-Based Diet.” Journal of Animal Science, vol. 92, 2014, pp. 1531 – 1536.

Bringas-Lantigua, M., et al. “Influence of Spray-Dryer Air Temperatures on Encapsulated Mandarin Oil.” Drying Technology, vol. 29, 2011, pp. 520–526.

Burtscher, J., et al. “Mitochondrial Stress and Mitokines in Aging.” Aging Cell, vol. 22, no. 2, 2023, e13770.

El-Hack, M. et al. “Integrating metabolomics for precision nutrition in poultry: optimizing growth, feed efficiency, and health”. Frontiers in Veterinary Science, Sec. Animal Nutrition and Metabolism, Volume 12 – 2025. https://doi.org/10.3389/fvets.2025.1594749

Elolimy, Ahmed A., et al. “Effects of Microencapsulated Essential Oils and Seaweed Meal on Growth Performance, Digestive Enzymes, Intestinal Morphology, Liver Functions, and Plasma Biomarkers in Broiler Chickens.” Journal of Animal Science, vol. 103, 2025, p. skaf092, https://doi.org/10.1093/jas/skaf092.

Fernández Miyakawa, Mariano E., et al. “How Did Antibiotic Growth Promoters Increase Growth and Feed Efficiency in Poultry?” Poultry Science, vol. 103, no. 2, 2024, article 103136. https://doi.org/10.1016/j.psj.2023.103136

Gaskins, H. Rex, C. T. Collier, and D. B. Anderson. “Antibiotics as Growth Promotants: Mode of Action.” Animal Biotechnology, vol. 13, no. 1, 2002, pp. 29 – 42.

Gharsallaoui, A., et al. “Applications of Spray-Drying in Microencapsulation of Food Ingredients: An Overview.” Food Research International, vol. 40, no. 9, 2007, pp. 1107-21.

Gutiérrez-Chávez, Vanesa, et al. “Capsaicinoids and Capsinoids of Chilli Pepper as Feed Additives in Livestock Production: Current and Future Trends.” Animal Nutrition, vol. 22, 2025, pp. 483 – 501. https://doi.org/10.1016/j.aninu.2025.03.014.

Gupta, A., et al. “Capsaicin and Capsinoids: Recent Updates on Their Health Benefits and Mechanisms of Action.” Phytotherapy Research, vol. 36, no. 5, 2022, pp. 1898 – 1912.

Hu, Q., Li, X., Chen, F., Wan, R., Yu, C.-W., Li, J., McClements, D. J., & Deng, Z. (2020). “Microencapsulation of an essential oil (cinnamon oil) by spray drying: Effects of wall materials and storage conditions on microcapsule properties“. Journal of Food Processing and Preservation, 44(11). https://doi.org/10.1111/jfpp.14805

Khameneh, B., et al. “Mechanisms of Antibiotic Resistance Resensitization by Phytochemicals: Review.” Phytomedicine, vol. 85, 2021, p. 153529.

Kim, D. K., et al. “Effects of Capsicum and Curcuma on Necrotic Enteritis in Broilers.” Poultry Science, vol. 94, 2015, pp. 2314 – 2321.

Kim, J. S., et al. “Anti-inflammatory Effects of Plant-Derived Molecules via NF-κB and MAPK Pathways.” International Immunopharmacology, vol. 10, no. 3, 2010, pp. 306 – 314.

Lee, S. H., et al. “Allium Hookeri Extract Enhances Tight Junction Proteins in Broilers.” Journal of Animal Physiology and Animal Nutrition, vol. 101, no. 1, 2017, pp. e48 – e56.

Li, X., et al. “Capsicum Oleoresin Supplementation Improves Digestive Enzyme Activity and Gut Morphology in Broilers.” Poultry Science, vol. 101, no. 7, 2022, p. 101844.

Lin, J. “Effect of Antibiotics on the Intestinal Microbiota and Their Role in Animal Growth.” Animal Biotechnology, vol. 25, no. 3, 2014, pp. 149 – 157.

Lillehoj, H., et al. “Phytochemicals as Antibiotic Alternatives to Promote Growth and Enhance Host Health.” Veterinary Research, vol. 49, no. 76, 2018.

Liu, Y., et al. “Dietary Capsicum Extract Enhances Intestinal Barrier Function and Growth in Pigs.” Journal of Animal Science, vol. 91, 2013, pp. 518 – 525.

Long, L., et al. “Phytogenic Feed Additives Modulate Intestinal Immunity and Antioxidant Status in Pigs and Poultry.” Frontiers in Veterinary Science, vol. 8, 2021, p. 620998.

Muurinen, J., et al. “Mushroom Powder Supplementation Increases Antibiotic Resistance Gene Mobility in Pig Feces.” Frontiers in Microbiology, vol. 12, 2021, p. 676678.

Niewold, T. A. “The Non-antibiotic Anti-inflammatory Effect of Antimicrobial Growth Promoters, the Real Mode of Action? A Hypothesis.” Poultry Science, vol. 86, 2007, pp. 605 – 609.

Perry, F., C. N. Johnson, L. Lahaye, E. Santin, D. R. Korver, M. H. Kogut, and R. J. Arsenault. “Protected Biofactors and Antioxidants Reduce the Negative Consequences of Virus and Cold Challenge by Modulating Immunometabolism via Changes in the Interleukin-6 Receptor Signaling Cascade in the Liver.” Poultry Science, vol. 103, no. 9, 2024, article 104044. https://doi.org/10.1016/j.psj.2024.104044

Rahman, Md, et al. “Insights in the Development and Uses of Alternatives to Antibiotic Growth Promoters in Poultry and Swine Production.” Antibiotics, vol. 11, no. 6, 2022, p. 766, https://doi.org/10.3390/antibiotics11060766.

Rauw, W.M. et al., “Review: Feed efficiency and metabolic flexibility in livestock”. Animal. Vol. 19 (2025) 101376. https://doi.org/10.1016/j.animal.2024.101376

Reda, F. M., et al. “Capsicum Extract Supplementation Modulates Gut Microbiota and Performance in Japanese Quails.” Animal Feed Science and Technology, vol. 265, 2020, p. 114507.

Rosca, I., et al. “Capsaicin Induces Osmotic Stress in Gram-negative Pathogens.” Veterinary Sciences, vol. 7, no. 4, 2020, p. 172.

Sahin, K., et al. “Dietary Capsicum Extract Reduces Oxidative Stress in Heat-stressed Japanese Quails.” Poultry Science, vol. 95, no. 2, 2016, pp. 231 – 240.

Saleh, A. A., et al. “Herbal Extract Mixtures Improve Antioxidant Status and Performance in Broilers.” Poultry Science, vol. 97, no. 11, 2018, pp. 3927 – 3936.

Stevanović, Z. D., et al. „Essential oils as feed additives—Future perspectives”. Molecules, 23(7), 2018, pp1717.

Suganya, R., et al. “Phytochemicals in Combination with Antibiotics: Antimicrobial Resistance Breakers.” Antibiotics, vol. 11, 2022, p. 123.

Zhang, Benyuan et al. “Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases.” Diabetes & Metabolism Journal vol. 48,1, 2024, pp. 1-18.

Zhan, Ru, et al. “Effects of Antibiotics on Chicken Gut Microbiota: Community Alterations and Pathogen Identification.” Frontiers in Microbiology, vol. 16, 2025, article 1562510. https://doi.org/10.3389/fmicb.2025.1562510

Zhang, Y., et al. “Effects of Vanillin, Thymol, and Eugenol on Glucose and Lipid Metabolism via TRPV1 Activation.” Journal of Agricultural and Food Chemistry, vol. 65, no. 13, 2017, pp. 2719 – 2727.

By Dr. Inge Heinzl, Editor, and Predrag Persak, Regional Technical Manager North Europe

For profitable pig production, efficient energy metabolism is essential. Every kilojoule consumed must be wisely spent – on maintenance, growth, reproduction, or defense. An impacted energy metabolism due to disease or stress impacts animal performance and farm profitability.

Different faces of energy

Energy metabolism determines how efficiently pigs convert feed into body mass. The Gross energy (GE) of the diet, which the use of a calorimeter can determine, is progressively reduced by losses in feces (→digestible energy – DE), urine, gases (→metabolizable energy – ME), and heat, resulting in the →net energy (NE), which is then available for maintenance and performance (growth, milk…).

The requirements for maintenance include the minimum energy that an organism needs to maintain essential functions under standardized conditions and at complete rest. This includes respiration, thermoregulation, tissue turnover, and immune system activity. Only energy in excess of these needs is available for performance. The ratio between additional retained energy and additional energy intake defines the incremental efficiency of nutrient utilization. Under normal conditions, healthy, fast-growing pigs display high incremental efficiencies for both protein and energy deposition by channeling energy efficiently into lean tissue and approximately 25-30% of the metabolizable energy from the feed is used for maintenance, 20-25% for lean gain, and the rest for fat deposition, driving daily gain and carcass quality (Patience, 2019).

However, disease, immune stress, and suboptimal environmental conditions can disrupt this delicate balance, diverting nutrients from growth to survival processes (Obled, 2003). The activation of the immune system leads to reduced feed efficiency, slower growth, and inferior meat quality.

Disease generates costs

The health challenge of disease causes energy loss through several key mechanisms (Patience, 2019).

1. The activation of the immune system becomes an energetic priority. It consumes significant amounts of energy and nutrients, such as glucose and specific amino acids, to produce immune cells and acute-phase proteins, such as haptoglobin and CRP, and to combat pathogens. The nutrients are redirected away from performance toward immune defense, i.e., less energy available for growth performance or even a mobilization of body reserves (fat deposits). A study conducted by Huntley et al. (2017) showed a 23.6% higher requirement for metabolizable energy to activate and maintain the immune system, resulting in a 26% lower ADG.
2. Physiological responses to disease, such as fever (heat production), shivering, or increased physical activity due to discomfort or listlessness, require energy.
3. Additional lower feed intake due to reduced appetite, leading to less energy consumption and intensifying the problem of energy repartitioning.

Environmental challenges are energy-consuming

Besides environmental conditions that cause disease due to high pathogenic pressure, environmental challenges are often related to thermoregulation.

1. Cold stress

In the case of cold stress, the ambient temperature falls below the pig’s lower critical temperature. The animal must spend extra energy to produce heat and maintain a constant body temperature. Alternatively, it can achieve this through shivering (muscle friction generates heat) and the release of thyroid hormones, which increase the metabolic rate and boost body temperature. Another possibility is huddling with other pigs. If the pigs eat more to gain extra energy for warmth, they increase production costs.

2. Heat stress

Excessive temperature leads to heat stress, and the animals attempt to cope through several mechanisms. Increased respiratory evaporation by panting is energy-intensive. Other possibilities are lying spread out on cool surfaces (conduction), seeking shade, and reducing physical activity to minimize heat production. To reduce metabolic heat production, pigs decrease their feed intake; however, this results in an energy deficit and likely mobilizes body reserves, especially in lactating sows.

3. Poor housing and management

High ventilation rates, draughts, wet floors, high stocking densities, and, too often, mixing of pigs are other stressors that require adequate energy-consuming responses. Also, an environment that facilitates excessive heat loss, e.g., through cold concrete floors, constrains the pigs to expend more ME to compensate. Poor-quality air with high levels of harmful gases, such as ammonia or hydrogen sulfide, or dust can lead to respiratory issues and energy expenditure for immune defense.

What are the detailed consequences?

Energy required for immune defense cannot be used for the production of meat, milk, or eggs. Several energy-consuming processes are triggered during an immunological challenge.

Glucose, an important energy source

Several scientists (Spurlock, 1997; Rigobelo and Ávila, 2011) have stated that glucose is primarily used to meet the increased energy demands of an activated immune system. According to Kvidera et al. (2017), the reason might be that stimulated leucocytes change their metabolism from oxidative phosphorylation to aerobic glycolysis (Palsson-McDermott and O’Neill, 2013). A trial conducted by Kvidera et al. (2017) confirmed the high need for glucose. In their trial with E. coli LPS-challenged crossbred gilts, they measured the amount of glucose required to maintain normal blood glucose levels (euglycemia). They calculated that an acutely and intensely activated immune system requires 1.1 g of glucose/kg body weight0.75/h. As they obtained similar results in ruminants (Kvidera et al., 2016 and 2017), they regard this glucose requirement as conserved across species and physiological states. In a confirming study, McGilvray and coworkers (2018) observed a significant (P<0.01) decrease in blood glucose in pigs after injection of E. coli LPS.

A further energy-consuming process is the increase in body temperature (fever): To increase body temperature by 1°C, the metabolic rate must be raised by 10-12.5% (Evans et al., 2015). 

Influence on protein metabolism

Stimulation of the immune system in growing pigs may lead to a redistribution of amino acids from protein retention to immune defense. Amino acids are needed as a ‘substrate’ to synthesize immune system metabolites, such as acute-phase proteins (e.g., haptoglobin, a-fibrinogen, antitrypsin, lipopolysaccharide-binding protein, C-reactive protein, and others (Rakhshandeh and De Lange, 2011)), immunoglobulins, and glutathione (Reeds and Jahoor, 2001). This impacts the requirements for amino acids quantitatively but also qualitatively, i.e., the amino acid profile. Various studies indicated an increased need for Methionine, cysteine, branched-chain amino acids (BCAAs), aromatic amino acids, Threonine, and Glutamine during immune system stimulation (Reeds et al., 1994; Melchior et al., 2004; Calder et al., 2006; Rakhshandeh and de Lange, 2011; Rakhshandeh et al., 2014).

If the required amino acids are not available, they must be either synthesized or obtained from body protein. This costs energy, leads to muscle mass degradation, and causes an imbalance in amino acid levels. Excess amino acids are catabolized, resulting in an increase in blood urea nitrogen (BUN). McGilvray et al. (2018), e.g., observed a 25% increase in BUN in their study, in which they stimulated pigs’ immune systems with LPS.

Another possibility is using amino acids as energy sources. L-Glutamine, for example, is a crucial energy source for immune cells and the primary energy substrate for mucosal cells (Mantwill, 2025).

Carcass and meat quality

As already mentioned, immune stimulation or disease leads to protein degradation. Plank and Hill (2000) reported a loss of up to 20% of body protein (mainly skeletal muscle) in critically ill humans over 3 weeks. This protein degradation influences carcass yield and quality by reducing the amount of muscle meat.

Another effect is a decrease in the muscle cross-sectional area of fibers and a significant shift from the myosin heavy chain (MHC)-II towards the MHC-I type (Gilvray et al, 2019)

How can feed additives support pigs in health challenges?

Health challenges can occur due to infections by bacteria, viruses, fungi, or protozoa, as well as due to myco-, exo-, or endotoxins. Phytomolecules-based and toxin-binding can help animals cope with these health challenges.

Phytomolecules have several health-supporting effects

Phytomolecules can support animals in the case of a health challenge by directly fighting bacteria – antimicrobial effect (Burt, 2004; Rowaiye et al., 2025), scavenging free radicals – antioxidant effect (Saravanan et al., 2025; Dhir, 2022), or mitigating infection – anti-inflammatory effect (Saravanan et al., 2025). 

A trial with the phytomolecules-based product Ventar D demonstrated its antimicrobial and microbiome-modulating effects (Heinzl, 2022). The product clearly reduced the populations of Salmonella enterica, E. coli, and Clostridium perfringens but spared the beneficial lactobacilli.

The anti-inflammatory effects of phytomolecules inhibit the activity of pro-inflammatory cytokines and chemokines from endotoxin-stimulated immune cells and epithelial cells (Lang et al., 2004; Lee et al., 2005; Liu et al., 2020), and there is an indication that the anti-inflammatory effects might be mediated by blocking the NF-κB activation pathway (Lee et al., 2005). A trial confirmed this thesis by showing a dose-dependent reduction of NFκB activity in LPS-stimulated mouse cells (-11% & -54% with 50 & 200 ppm Ventar D, respectively) (Figure 1).

Additionally, Ventar D increases interleukin-10, a cytokine with anti-inflammatory properties, and decreases interleukin-6, a pro-inflammatory cytokine. The result is a dose-dependent decline in the ratio of IL-6 to IL-10 (Figure 2), indicating the effectiveness of the product.

The effects of Ventar D, which support the immune system and redirect energy to enhance growth performance, result in higher daily gains and improved feed conversion. This was observed in a trial conducted on a commercial farm in Germany, using, on average, 26-day-old weaned piglets with a mean body weight of approximately 8 kg. Just after weaning, young animals experience stress (new feed, new groups, and separation from the dam) and are more susceptible to disease.

Two groups of piglets were fed either the regular feed of the farm (Control) or the regular feed + 100 g Ventar per MT of feed. The results for final weight and FCR are shown in Figures 3 and 4

Toxin-binding products support animals against health challenges caused by toxins

As mentioned, various toxins, including myco-, endo-, and exotoxins, can harm animals. The danger of mycotoxins lurks in many feeds, and exo- and endotoxins derive from bacteria. Toxin-binding products, possibly supplemented with phytomolecules that support health (e.g., liver protection), can help animals cope with these challenges.

Solis Max 2.0, a toxin solution containing bentonite and phytomolecules, showed excellent binding performance for myco- and endotoxins (Figures 5 and 6).

Trial with endotoxins

Two samples were prepared: one with only 25 EU (1 EU equivalent to approximately 100 pg or 10,000 cells) of LPS of E. coli O55:B5 LPS/mL solution, and one with the same concentration of LPS but also containing 700 mg Solis Max 2.0/mL.

Solis Max 2.0 bound about 80% of endotoxin.

Trial with mycotoxins

In another in vitro trial, the binding capacity of Solis Max 2.0 for six different kinds of mycotoxins was evaluated. For that purpose, samples with 800 ppb AFB1, 400 ppb OTA, 800 ppb DON, 300 ppb T2, 2,000 ppb FB1, or 1,200 ppb ZEN were prepared, and Solis max was added at two inclusion rates, one corresponding to 1 kg/t, the other to 2 kg/t. The binding capacities ranged from 40.7% for OTA to 96% for AFB1, with the lower inclusion rate, and from 61.5% for OTA to 99% for AFB1, with the higher inclusion rate.

Health support by toxin-binding solutions improves performance

The mitigating effects of Solis Max concerning the negative impact of toxins are also reflected in performance. A trial involving 24 female weaned piglets was conducted to evaluate the mitigating effects of Solis Max in the event of a challenge with a naturally contaminated diet (3,400 ppb of DON and 700 ppb of ZEA). Solis Max was added to one half of the challenged piglets. The addition of Solis Max to the contaminated diet not only compensates for growth performance parameters, such as weight gain and feed conversion, but also for Vulva and tail necrosis scores. The results are shown in Figures 7-11.

Tools are available to prevent the unnecessary expenditure of energy for immune protection

As the various references in the article demonstrate, health challenges such as pathogens or toxins not only spoil the appetite of animals but also require energy due to the activation of the immune system. Products based on phytomolecules, as well as toxin solutions, can help animals cope with these challenges and conserve energy for improved performance.

References:

Balli, Swetha, Karlie R. Shumway, and Shweta Sharan. “Physiology, Fever.” StatPearls [Internet]., September 4, 2023. https://www.ncbi.nlm.nih.gov/books/NBK562334/. 

Burt, Sara. “Essential Oils: Their Antibacterial Properties and Potential Applications in Foods—a Review.” International Journal of Food Microbiology 94, no. 3 (August 2004): 223–53. https://doi.org/10.1016/j.ijfoodmicro.2004.03.022. 

Calder, Phillip C. “Branched-Chain Amino Acids and Immunity ,.” The Journal of Nutrition 136, no. 1 (January 2006). https://doi.org/10.1093/jn/136.1.288s. 

Dhir, Vivek. “Emerging Prospective of Phytomolecules as Antioxidants against Chronic Diseases.” ECS Transactions 107, no. 1 (April 24, 2022): 9571–80. https://doi.org/10.1149/10701.9571ecst. 

Evans, Sharon S., Elizabeth A. Repasky, and Daniel T. Fisher. “Fever and the Thermal Regulation of Immunity: The Immune System Feels the Heat.” Nature Reviews Immunology 15, no. 6 (May 15, 2015): 335–49. https://doi.org/10.1038/nri3843. 

Heinzl, Inge. “Efficient Microbiome Modulation with Phytomolecules.” EW Nutrition, June 9, 2023. https://ew-nutrition.com/pushing-microbiome-in-right-direction-phytomolecules/. 

Huntley, Nichole F., John F. Patience, and C. Martin Nyachoti. “Immune Stimulation UPS Maintenance Energy Requirements.” National Hog Farmer.com, September 28, 2017. https://www.nationalhogfarmer.com/hog-health/immune-stimulation-ups-maintenance-energy-requirements. 

Kvidera, S. K., E. A. Horst, M. Abuajamieh, E. J. Mayorga, M. V. Sanz Fernandez, and L. H. Baumgard. “Technical Note: A Procedure to Estimate Glucose Requirements of an Activated Immune System in Steers.” Journal of Animal Science 94, no. 11 (November 1, 2016): 4591–99. https://doi.org/10.2527/jas.2016-0765. 

Kvidera, S.K., E.A. Horst, M. Abuajamieh, E.J. Mayorga, M.V. Sanz Fernandez, and L.H. Baumgard. “Glucose Requirements of an Activated Immune System in Lactating Holstein Cows.” Journal of Dairy Science 100, no. 3 (March 2017): 2360–74. https://doi.org/10.3168/jds.2016-12001. 

LANG, A. “Allicin Inhibits Spontaneous and Tnf-$alpha; Induced Secretion of Proinflammatory Cytokines and Chemokines from Intestinal Epithelial Cells.” Clinical Nutrition, May 2004. https://doi.org/10.1016/s0261-5614(04)00058-5. 

Lee, Seung Ho, Sun Young Lee, Dong Ju Son, Heesoon Lee, Hwan Soo Yoo, Sukgil Song, Ki Wan Oh, Dong Cho Han, Byoung Mog Kwon, and Jin Tae Hong. “Inhibitory Effect of 2′-Hydroxycinnamaldehyde on Nitric Oxide Production through Inhibition of NF-ΚB Activation in RAW 264.7 Cells.” Biochemical Pharmacology 69, no. 5 (March 2005): 791–99. https://doi.org/10.1016/j.bcp.2004.11.013. 

Liu, S. D., M. H. Song, W. Yun, J. H. Lee, H. B. Kim, and J. H. Cho. “Effect of Carvacrol Essential Oils on Growth Performance and Intestinal Barrier Function in Broilers with Lipopolysaccharide Challenge.” Animal Production Science 60, no. 4 (January 22, 2020): 545–52. https://doi.org/10.1071/an18326. 

Liu, S. D., M. H. Song, W. Yun, J. H. Lee, H. B. Kim, and J. H. Cho. “Effect of Carvacrol Essential Oils on Growth Performance and Intestinal Barrier Function in Broilers with Lipopolysaccharide Challenge.” Animal Production Science 60, no. 4 (January 22, 2020): 545–52. https://doi.org/10.1071/an18326. 

Mantwill, Elke. “Eiweiß & Immunsystem.” sportärztezeitung, April 10, 2025. https://sportaerztezeitung.com/rubriken/ernaehrung/9197/eiweiss-immunsystem/. 

McGilvray, Whitney D, David Klein, Hailey Wooten, John A Dawson, Deltora Hewitt, Amanda R Rakhshandeh, Cornelius F de Lange, and Anoosh Rakhshandeh. “Immune System Stimulation Induced byEscherichia ColiLipopolysaccharide Alters Plasma Free Amino Acid Flux and Dietary Nitrogen Utilization in Growing Pigs1.” Journal of Animal Science 97, no. 1 (October 11, 2018): 315–26. https://doi.org/10.1093/jas/sky401. 

Melchior, D., B. Sève, and N. Le Floc’h. “Chronic Lung Inflammation Affects Plasma Amino Acid Concentrations in Pigs.” Journal of Animal Science 82, no. 4 (April 1, 2004): 1091–99. https://doi.org/10.2527/2004.8241091x. 

Obled, C. “Amino Acid Requirements in Inflammatory States.” Canadian Journal of Animal Science 83, no. 3 (September 1, 2003): 365–73. https://doi.org/10.4141/a03-021. 

Palsson‐McDermott, Eva M., and Luke A. O’Neill. “The Warburg Effect Then and Now: From Cancer to Inflammatory Diseases.” BioEssays 35, no. 11 (September 20, 2013): 965–73. https://doi.org/10.1002/bies.201300084. 

Pastorelli, H., J. van Milgen, P. Lovatto, and L. Montagne. “Meta-Analysis of Feed Intake and Growth Responses of Growing Pigs after a Sanitary Challenge.” Animal 6, no. 6 (2012): 952–61. https://doi.org/10.1017/s175173111100228x. 

Patience, John. “One of the Most Important Decisions in Swine Production: Dietary Energy Level – Dr. John Patience by The Swine It Podcast Show.” Spotify for Creators, December 2, 2019. https://anchor.fm/swineitpodcast/episodes/One-of-the-most-important-decisions-in-swine-production-dietary-energy-level—Dr–John-Patience-e99j9u. 

Plank, Lindsay D., and Graham L. Hill. “Sequential Metabolic Changes Following Induction of Systemic Inflammatory Response in Patients with Severe Sepsis or Major Blunt Trauma.” World Journal of Surgery 24, no. 6 (June 2000): 630–38. https://doi.org/10.1007/s002689910104. 

Rakhshandeh, A., and C.F.M. de Lange. “Evaluation of Chronic Immune System Stimulation Models in Growing Pigs.” Animal 6, no. 2 (2012): 305–10. https://doi.org/10.1017/s1751731111001522. 

Rakhshandeh, A., and C.F.M. De Lange. “Immune System Stimulation in the Pig: Effect on Performance and Implications for Amino Acid Nutrition.” Essay. In Manipulating Pig Production XIII, 31–46. Werribee, Victoria, Australia: Australasian Pig Science Association Incorporation, 2011. 

Rakhshandeh, Anoosh, John K. Htoo, Neil Karrow, Stephen P. Miller, and Cornelis F. de Lange. “Impact of Immune System Stimulation on the Ileal Nutrient Digestibility and Utilisation of Methionine plus Cysteine Intake for Whole-Body Protein Deposition in Growing Pigs.” British Journal of Nutrition 111, no. 1 (January 14, 2014): 101–10. https://doi.org/10.1017/s0007114513001955. 

Reeds, P., and F. Jahoor. “The Amino Acid Requirements of Disease.” Clinical Nutrition 20 (June 2001): 15–22. https://doi.org/10.1054/clnu.2001.0402. 

Reeds, Peter J, Carla R Fjeld, and Farook Jahoor. “Do the Differences between the Amino Acid Compositions of Acute-Phase and Muscle Proteins Have a Bearing on Nitrogen Loss in Traumatic States?” The Journal of Nutrition 124, no. 6 (June 1994): 906–10. https://doi.org/10.1093/jn/124.6.906. 

Rigobelo, E. Cid, and F. A. De Ávila. “Hypoglycemia Caused by Septicemia in Pigs.” Essay. In Hypoglycemia – Causes and Occurrences., 221–38. London, UK: InTechOpen, 2011. 

Rowaiye, Adekunle, Gordon C. Ibeanu, Doofan Bur, Sandra Nnadi, Ugonna Morikwe, Akwoba Joseph Ogugua, and Chinwe Uzoma Chukwudi. “Phyto-Molecules Show Potentials to Combat Drug-Resistance in Bacterial Cell Membranes.” Microbial Pathogenesis 205 (August 2025): 107723. https://doi.org/10.1016/j.micpath.2025.107723. 

Saravanan, Haribabu, Maida Engels SE, and Muthiah Ramanathan. “Phytomolecules Are Multi Targeted: Understanding the Interlinking Pathway of Antioxidant, Anti Inflammatory and Anti Cancer Response.” In Silico Research in Biomedicine 1 (2025): 100002. https://doi.org/10.1016/j.insi.2025.100002. 

Spurlock, M E. “Regulation of Metabolism and Growth during Immune Challenge: An Overview of Cytokine Function.” Journal of Animal Science 75, no. 7 (1997): 1773–83. https://doi.org/10.2527/1997.7571773x. 

Suchner, U., K. S. Kuhn, and P. Fürst. “The Scientific Basis of Immunonutrition.” Proceedings of the Nutrition Society 59, no. 4 (November 2000): 553–63. https://doi.org/10.1017/s0029665100000793.

Recently, The Poultry Site’s Sarah Mikesell interviewed Predrag Persak, EW Nutrition’s Regional Technical Manager for Northern Europe. The conversation covered topics as wide as sustainability and challenges in poultry production, and as narrow as intestinal permeability. Thanks to The Poultry Site for the great talk!

Watch the video

Sarah Mikesell, The Poultry Site: Hi, this is Sarah Mikesell with The Poultry Site, and today we are here with Predrag Peršak. He is the Regional Technical Manager for Northern Europe with EW Nutrition. Thanks for being with us today, Predrag.

Predrag Peršak, EW Nutrition: Nice to be here, Sarah. Thank you for inviting me.

SM: Very good. It’s nice to visit with you. And today, Predrag and I are in Berlin, Germany, at an exclusive event for the poultry industry called Producing for the Future, which is sponsored by EW Nutrition. You are one of our speakers today, Predrag, so I’m going to ask you just a few questions to let everybody know a little bit about your presentation.

You’ve described animal nutrition as “never boring and never finished.” What makes this field so dynamic and constantly evolving for you?

PP: I’ve been in animal nutrition for about 25 years. And in those 25 years, I would say that not even half a year passed without something extraordinary happening. From genetics to animal husbandry, especially here in Europe, we also have a lot of pressure from consumers and slaughterhouses to adapt production to the needs of the customers.

Sustainability, sourcing raw materials, and the variety of raw materials available in Europe – and the constant development of new ones – make life for an animal nutritionist very, very interesting. It’s also very challenging, and through these challenges you learn a lot.

So, applying what we learned 20 years ago is simply not enough anymore. For someone who wants to be challenged every day with new things, this is definitely the right industry to be in – especially now.

SM: Excellent. Can you explain your holistic approach to animal nutrition and how considering multiple factors benefits practical applications on farms?

PP: The concept of a holistic approach in animal nutrition is not new. But for me – being both a veterinarian and a nutritionist – it means having deeper insight into the animal itself, into all the metabolic processes, and also into the external influences: husbandry, genetics, diseases, and management. Looking at how all of these interact, we can only really solve problems by looking at the animal as a whole system.

The same applies to feed production. You cannot look at a feed mill as just one compartment. You have to look at sourcing raw materials, their quality, how they are processed – milling, pelleting, and other technologies – and then see how that feed performs on the farm.

So, a holistic approach can be applied both from the animal perspective and from the feed production perspective, across all steps and processes. This is something we use and promote daily in our work with customers.

SM: Very good. You’ve worked with unconventional protein and fiber sources. We’re hearing a lot more about that recently. What are those, and what potential do they bring to animal nutrition?

PP: When I talk about unconventional protein and fiber sources, we need to remember that the global feed production scene is very diverse. What applies in the U.S. or Brazil does not necessarily apply in Europe or the Far East.

Here in Europe, we try to use not by-products but co-products of food production. For example, different fractions of rapeseed or sunflower meal, which are widely produced in Europe but not often used by mainstream nutritionists due to certain limitations. By finding the right processing methods and combining them with technologies, we can make these unconventional materials usable in mainstream nutrition.

The same goes for fiber sources. Both fermentable and structural fibers are increasingly important for intestinal and digestive development, as well as for overall animal health. So, processing fibers in ways that maximize usability while minimizing negative effects is a big part of my work.

SM: From a cost standpoint for producers, are those lower-cost inputs, or just alternatives they need to look at?

PP: In Germany we have a perfect expression for this: “yes and no.” There is always pressure on price, especially in poultry, because food must be accessible to everyone. But at the same time, food must not harm the environment or human health, and we should use all resources not fit for humans but still usable for animals.

So, it’s not only about cost – about availability and sustainability. Working with just two, three, or five raw materials for a long time is not the way forward. The way forward is to think of everything that can be used properly, for the benefit of the animals, and ultimately to produce enough food for the world.

Also, using locally available products is important. Feed production is very diverse around the world—raw materials in Southeast Asia differ completely from those in Europe, Brazil, or the U.S. Using technologies to enable the use of locally produced by-products makes production not only sustainable, but also economically viable for local communities. That’s really the core of the feed industry: using what is produced locally.

SM: Interesting. Very cool. How does your interdisciplinary work across poultry, pigs, and ruminants give you unique insights that might be missed with a narrower focus?

PP: I come from a small feed mill in a small country, Croatia. There, you don’t have deep specialization by species or even by category, as you find in larger markets. Specialization has its advantages, but it can also limit creativity and “outside-the-box” thinking.

By working with ruminants, I learned about fermentation processes – knowledge that can be applied to pigs and even to poultry. For example, fermentation can reduce anti-nutritional factors, allowing higher inclusion levels of certain raw materials in poultry diets.

With pigs, fermentation of fibers – especially in piglets – is crucial, and some of that knowledge could be applied to turkeys, where we still face health issues.

So, working across species demands a lot – it leaves little time for other things – but it opens up unique perspectives and cross-species applications that benefit the entire livestock industry.

SM: I was talking with someone yesterday about mycotoxins – there’s a lot of research in pigs but less in poultry. That’s kind of what you’re talking about, right? Applying knowledge across species?

PP: Absolutely. We’re focused now on poultry, but we can learn from poultry too – not only about feeding but also about farm management, biosecurity, and more. These lessons can also apply to pigs or ruminants.

It’s all holistic – you cannot solve everything with nutrition alone. It’s always a package.

SM: You presented today about the importance of intestinal permeability. Why is it important, and how can understanding it impact animal health and performance outcomes?

PP: Intestinal permeability is one of the key features we use to describe gut health. Personally, I’m very practical. For 20 years we’ve talked about “gut health,” but the real question for veterinarians and nutritionists is: what do we actually do with that knowledge?

In my presentation, I explained intestinal permeability as a “point of no return” in gut health. When leaky gut develops, everything else can deteriorate – faster or slower – but it won’t return to normal without intervention.

By comparing how different stressors or pathogens impact intestinal permeability, we can better understand severity and decide where to focus. Nutritionists already pay attention to thousands of factors, but we need to identify the most impactful ones. That was my key message: focus on the most important drivers.

SM: And leaky gut has really become something the whole industry is talking about, right? I’ve even seen it in human health – my doctor has posters about it.

PP: Exactly. Across cows, pigs, and poultry, leaky gut is getting a lot of attention. It’s a physiological or pathophysiological feature that marks the point of no return.

We can talk about dysbiosis and all the causes, but once you reach leaky gut, you understand where intervention is needed. And it’s not just hype. For example, recently Nature published research showing certain types of human bone marrow conditions are linked to leaky gut and microbial influence on blood processes.

So, this is not a passing trend. It’s fundamental. And once we solve one issue, another door opens. That’s why this industry is never boring.

SM: Very good. Well, thank you for all the information today, Predrag.

PP: Thank you, Sarah. It was a pleasure to talk with you.

Watch the video on The Poultry Site.

Author: Ajay Bhoyar, Sr. Global Technical Manager, EW Nutrition

As the poultry industry seeks economical and nutritious feed ingredients, distillers’ dried grains with solubles (DDGS), a co-product of grain-based ethanol production, presents a valuable option providing beneficial protein, energy, water-soluble vitamins, xanthophylls, and linoleic acid. However, the inherent variability in DDGS nutrient composition and high fiber content can pose challenges for consistent inclusion in poultry feeds. The strategic use of feed enzymes has become a significant area of focus to overcome these limitations and further enhance the nutritional value of DDGS in poultry diets. This article will explore the optimization of DDGS utilization in poultry feeds by emphasizing the inclusion of xylanase enzyme that can efficiently degrade the insoluble arabinoxylans. By understanding the factors affecting DDGS quality and strategically employing xylanase, poultry producers can potentially achieve higher inclusion rates of this readily available byproduct, aiming to reduce feed costs while maintaining or even improving production performance and overall health.

Price competitiveness of DDGS

The price of DDGS relative to other feed ingredients, primarily corn and soybean meal, is a significant factor in its global utilization. DDGS often partially replaces these traditional energy (corn) and protein (soybean meal) sources in animal feeds, leading to significant diet cost savings for poultry producers. DDGS contains a high amount of a combination of energy, amino acids, and phosphorus. However, it is usually undervalued as its price is mainly determined based on the prevailing prices of corn and soybean meal.

Variability in the nutritional quality of DDGS

The nutrient composition of DDGS varies based on the starting grain, ethanol production methods, and drying processes. Generally, DDGS contains high levels of protein, fiber, and minerals, with varying amounts of fat and starch depending on the type of grain used and how it is processed. DDGS has a reputation for having variable nutrient composition, protein quality, and a high content of mycotoxins (Stein et al., 2006; Pedersen et al., 2007; Anderson et al., 2012). High quantities of DDGS in feed increase dietary fiber, adversely affecting nutrient digestibility.

The variations in production methods lead to significant differences in the following nutritional components of DDGS:

Crude Fat: This is one of the most variable components, ranging from 5 to 9 percent in reduced-oil DDGS and greater than 10 percent in traditional high-oil DDGS.

Energy: The apparent metabolizable energy (AMEn) for poultry varies among DDGS sources. Fiber digestibility and the digestibility of the extracted oil also contribute to this variability. The high temperatures during the drying stage of DDGS production accelerate lipid peroxidation, forming breakdown products from the fats. This peroxidation contributes to the changes and variability observed in the fat component of DDGS and is a factor that can affect nutrient digestibility and overall energy value.

Crude Protein and Amino Acids (especially Lysine): While crude protein content might not always increase inversely with fat reduction, the digestibility of amino acids, especially lysine, can be affected by drying temperatures. Lysine digestibility of DDGS is a primary concern of poultry nutritionists due to the susceptibility of this amino acid to Maillard reactions during the drying process of DDGS, which can reduce both the concentration and digestibility of lysine (Almeida et al. 2013). Prediction equations have been developed to accurately estimate actual AMEn and standardized ileal digestible amino acid content of DDGS sources based on chemical composition.

Phosphorus: The phosphorus content can vary depending on the amount of Condensed Distiller’s Solubles (CDS) added. The bioavailability of phosphorus can also be influenced by processing. The phosphorus content in the corn DDGS may vary from 0.69 to 0.98 % (Olukosi and Adebiyi, 2013).

Fiber: The neutral detergent fiber (NDF) content is another variable component. Differences in processing conditions among ethanol plants can lead to variations in fiber digestibility.

Table 1. Variation in composition of corn DDGS sources (dry matter basis; adapted from (Pederson et al., 2014)

Analyte	Average	Range
Moisture %	8.7	6.5 – 12.5
Crude protein %	31.4	27.1 – 36.4
Crude fiber %	7.7	6.4 – 9.5
Ether Extract %	9.1	6.5 – 11.8
NDF %	35.1	30.2 – 39.7
ADF %	10.1	8.9 – 11.9

Nonstarch Polysaccharides (NSP) in DDGS

Non-starch polysaccharides (NSP) are a significant component of DDGS. The NSP profile of DDGS is crucial for understanding its digestibility and energy content.​ The corn DDGS has a complex fiber structure that may limit its digestibility in swine and poultry. NSPs in corn DDGS represent 25-34% of its composition, primarily insoluble (Pedersen et al. 2014). The complexity of the fiber structure in corn DDGS makes it more challenging to degrade with enzymes than wheat DDGS. Therefore, while including DDGS in the poultry feeds, choosing an exogenous xylanase enzyme that is highly efficient in breaking down both soluble and insoluble arabinoxylans is essential for maximum energy utilization.

Use of xylanase in DDGS diets for poultry

Supplementing exogenous enzymes in swine and poultry diets have numerous potential benefits including: reduction of digesta viscosity to enhance lipid and protein digestion; increase the metabolizable energy content of the diet; increase feed intake, growth rate and feed conversion; decreased size and alter the microbial population of the gastrointestinal tract; reduce water consumption and water content of excreta in poultry; reduce the amount of excreta as well as ammonia, nitrogen and phosphorus content (Khattak et al., 2006). The selection of a specific enzyme must be based on the type and availability of the target substrate in the diet.

The improved energy utilization of DDGS in poultry can be achieved through the enzymatic degradation of fiber (NSP). Nonstarch polysaccharides within DDGS exist in matrices with starch and protein, so NSP degradation via exogenous enzymes can also release other nutrients for subsequent digestion and absorption (Jha et al. 2015).

The cell wall matrix in corn DDGS is more complex. Moreover, the most readily degradable arabinoxylan for the fiber-degrading enzymes is modified during DDGS production (Pedersen et al. 2014). Many studies reported a greater branch density and complexity of corn arabinoxylan than wheat (Bedford, 1995; Saulnier et al.,1995a; Jilek and Bunzel, 2013; Yang et al., 2013). These observations indicate that the fiber-degrading enzymes applied for the degradation of corn DDGS need to be targeted towards highly complex substrates. This calls for selecting xylanase, which effectively breaks down the insoluble arabinoxylans in diets.

Axxess XY: Highly effective xylanase in breaking down soluble and insoluble arabinoxylans

A bacterial GH10 family xylanase, like Axxess XY, is more beneficial in animal production due to their efficient mechanism of action, broader substrate specificity, and better thermostability. Generally, the GH10 xylanases exhibit broader substrate specificity and can efficiently hydrolyze various forms of xylan, including soluble and insoluble substrates. GH10 xylanases exhibit higher catalytic versatility and can catalyze the cleavage of the xylan backbone at the non-reducing side of substituted xylose residues, whereas GH11 enzymes require unsubstituted regions of the xylan backbone (Collins et al., 2005; Chakdar et al., 2016).

Fig.1. Activity of a bacterial GH10 xylanase against soluble and insoluble arabinoxylans

Axxess XY facilitates DDGS use and reduces the cost of broiler production.

Including xylanase enzyme, which is highly effective in breaking down soluble and insoluble arabinoxylans in poultry feeds, can reduce feed costs, allowing higher inclusion of DDGS while maintaining the bird’s commercial performance.

In a recently conducted 42-day trial at a commercial farm, Axxess XY maintained broiler performance with a 100 kcal/kg reduction in metabolizable energy and 8% use of Corn DDGS in a corn-SBM based diet (Figure 2). This significantly reduced feed cost/kg body weight.

Incorporating DDGS into poultry diets presents a sustainable and cost-effective solution, but its full potential is often limited by variability in nutrient composition and high fiber content. Xylanase enzymes, particularly those in the GH10 family like Axxess XY, can overcome these barriers by breaking down complex arabinoxylans and unlocking inaccessible nutrients. With proven benefits in energy utilization, nutrient digestibility, and overall production efficiency, xylanase inclusion emerges as a strategic approach to optimize DDGS usage, ultimately supporting economic and environmental sustainability goals in poultry production.

References

Almeida, F.N.; Htoo, J.K.; Thomson, J.; Stein, H.H. Amino acid digestibility of heat-damaged distillers’ dried grains with soluble fed to pigs. J. Anim. Sci. Biotechnol. 2013, 4, 2–11.

Bedford, M.R., 1995. Mechanism of action and potential environmental benefits from the use of feed enzymes. Anim. Feed Sci. Technol. 53, 145–155.

Chakdar, Hillol, Murugan Kumar, Kuppusamy Pandiyan, Arjun Singh, Karthikeyan Nanjappan, Prem Lal Kashyap, and Alok Kumar Srivastava. “Bacterial Xylanases: Biology to Biotechnology.” 3 Biotech 6, no. 2 (June 30, 2016). https://doi.org/10.1007/s13205-016-0457-z.

Collins, Tony, Charles Gerday, and Georges Feller. “Xylanases, Xylanase Families and Extremophilic Xylanases.” FEMS Microbiology Reviews 29, no. 1 (January 2005): 3–23. https://doi.org/10.1016/j.femsre.2004.06.005.

Jha, R.; Woyengo, T.A.; Li, J.; Bedford, M.R.; Vasanthan, T.; Zijlstra, R.T. Enzymes enhance degradation of the fiber–starch–protein matrix of distillers dried grains with solubles as revealed by a porcine in vitro fermentation model and microscopy. J. Anim. Sci. 2015, 93, 1039–1051.

Jilek, M.L., Bunzel, M., 2013. Dehydrotriferulic and dehydrodiferulic acid profiles of cereal and pseudocereal flours. Cereal Chem. J. 90, 507–514

Jones, C.K., Bergstrom, J.R., Tokach, M.D., DeRouchey, J.M., Goodband, R.D., Nelssen, J.L., Dritz, S.S., 2010. Efficacy of commercial enzymes in diets containing various concentrations and sources of dried distillers’ grains with solubles for nursery pigs. J. Anim. Sci. 88, 2084–2091.

Khattak, F.M., T.N. Pasha, Z. Hayat, and A. Mahmud. 2006. Enzymes in poultry nutrition. J. Anim. Pl. Sci. 16:1-7.

Olukosi, O.A., and A.O. Adebiyi. 2013. Chemical composition and prediction of amino acid content of maize- and wheat-distillers’ Dried Grains with Soluble. Anim. Feed Sci. Technol. 185:182-189.

Pedersen M. B., Dalsgaard S., Bach Knudsen K.E., Yu S., Lærke H.N., Compositional profile and variation of Distillers Dried Grains with Solubles from various origins with focus on non-starch polysaccharides, Animal Feed Science and Technology, Volume 197, 2014, Pages 130–14.

Saulnier, L., Vigouroux, J., Thibault, J.-F., 1995a. Isolation and partial characterization of feruloylated oligosaccharides from maize bran. Carbohydr. Res. 272,241–253.

Yang, J., Maldonado-Gómez, M.X., Hutkins, R.W., Rose, D.J., 2013. Production and in vitro fermentation of soluble, non-digestible, feruloylated oligo- andpolysaccharides from maize and wheat brans. J. Agric. Food Chem.

Yoon, S.Y., Yang, Y.X., Shinde, P.L., Choi, J.Y., Kim, J.S., Kim, Y.W., Yun, K., Jo, J.K., Lee, J.H., Ohh, S.J., Kwon, I.K., Chae, B.J., 2010. Effects of mannanase and distillers’ dried grain with solubles on growth performance, nutrient digestibility, and carcass characteristics of grower-finisher pigs. J. Anim. Sci. 88,181–191.

Conference Report

Achieving high performance and superior meat quality with preferably low investment – and here, we speak about feed costs, which account for up to 70% of the total costs – is a considerable challenge for pig producers. The following will focus on the effects of genetic enhancements and nutrient quality on overall pig performance.

Effect of body weight and gender on protein deposition

Based on Schothorst Feed Research recommendations for tailoring nutritional strategies to enhance feed efficiency and overall productivity, the following facts must be considered:

• Castrates, boars, and gilts have significantly different nutritional requirements due to variations in growth rates, body composition, and hormonal influences. For instance, testosterone significantly impacts muscle development and protein metabolism, increasing muscle mass in males. In contrast, ovarian hormones may inhibit muscle protein synthesis in females, contributing to differences in overall protein deposition. Boars, therefore, require higher protein levels to support muscle growth. Castrates typically have a higher FCR compared to gilts and boars due to higher feed intake. Split-sex feeding allows for diet adjustments to optimize growth rates and reduce feed costs per kilogram gained.
• Different body weight ranges: because puberty is delayed in modern genetics, we can produce heavier pigs without compromising carcass quality. Given that a finisher pig with 80-120 kg bodyweight consumes about half of the total feed of that pig, Dr. Fledderus concluded that extra profit could be realized with an extra feed phase diet for heavy pigs. Implementing multiple finisher diets can help reduce feed costs by allowing for lower nutrient concentrations, such as reducing the net energy and standardized ileal digestible lysine in later phases, without compromising performance.

Decision-making according to feedstuff prices

Least cost formulation is commonly used by nutritionists to formulate feeds for the lowest costs possible while meeting all nutrient requirements and feedstuff restrictions at the actual market prices of feedstuffs. However, diet optimization is more complex. The real question is, “How do you formulate diets for the lowest cost per kilogram of body weight gain?” You must always consider your specific situation, as economic results vary greatly and depend mainly on the prices of pork and feed and pig growth performance (e.g., feed efficiency, slaughter weight, and lean percentage).

How can you optimize your feeding strategy? Reducing net energy (NE) value will result in more fiber entering the diet. This makes sense if fiber by-products are cheaper than cereals. In contrast, an increase in the NE value will increase the inclusion of high-quality proteins and synthetic amino acids. It will use more energy from fat and less from carbohydrates.

The effects of diet composition on meat quality and fat composition also need to be considered.

How can nutrition improve meat quality?

Nutritional strategies not only improve the sensory attributes of pork but also enhance its shelf life, ultimately leading to higher consumer satisfaction and better marketability. Some of the factors Dr Fledderus considered included:

Improving fat quality

The source of dietary fat significantly impacts the quality of pork fat. Saturated fats tend to produce firmer fat, while unsaturated fats can lead to softer, less stable fat deposits. Diets high in unsaturated fats are more prone to lipid oxidation, negatively affecting shelf life and overall meat quality. The deposition of polyunsaturated fatty acids is only from dietary fat. Saturated fats in pork, partly originates from dietary fat and are also synthesized de novo. So, the amount of polyunsaturated fatty acids in pork depends on the content and composition of dietary fat, which can negatively affect the shelf life and perception of pork meat.

The iodine value (IV) is a measure of the degree of unsaturation in fats. A higher IV indicates a higher proportion of unsaturated fatty acids, leading to softer fat. Pork fat with an IV lower than 70 is considered high quality, as it tends to be firmer and more desirable for processing.

As per the American Oil Chemists Society, IV is calculated as:

IV = [C16:1] × 0.95 + [C18:1] × 0.86 + [C18:2] × 1.732 + [C18:3] × 2.616 + [C20:1] × 0.785 + [C22:1] × 0.723

(brackets indicate concentration (%) of C16:1 palmitoleic acid, C18:1 oleic acid, C18:2 linoleic acid, C18:3-linoleic acid, C20:1 eicosenoic acid, C22:1 erucic acid per crude fat)

Implications

Dr. Fledderus concluded that the pigs’ nutritional requirements are dynamic and influenced by factors such as required meat and fat quality, heat stress, slaughter weight, and genetic developments. Tailoring diets based on gender and body weight is crucial for optimizing protein deposition. Accurate information is essential to formulate diets that achieve optimum economic results, not just the least cost.

Continuous monitoring of feedstuff prices and nutritional content allows for timely adjustments in diet formulations, ensuring that producers capitalize on cost-effective ingredients while maintaining nutritional quality.

EW Nutrition’s Swine Academy took place in Ho Chi Minh City and Bangkok in October 2024. Dr. Jan Fledderus, Product Manager and Consultant at the S&C team at Schothorst Feed Research, with a strong focus on continuously improving the price/quality ratio of the diets for a competitive pig sector and one of the founders of the Advanced Feed Package, was a reputable guest speaker in these events.

Conference Report

During the recent EW Nutrition Swine Academies in Ho Chi Minh City and Bangkok, Dr. Jan Fledderus, Product Manager and Consultant at Schothorst Feed Research, discussed that much money is involved in a correct energy evaluation system. “Net energy is 70% of feed costs, and feed is about 70% of total costs.” Therefore, an accurate energy evaluation system is important as it will give:

• Flexibility to use different raw materials
• Reduction of formulation costs
• Best prediction of pig performance
• Match the available dietary energy requirement of the feed to the pig’s requirement

Energy evaluation systems for pigs

The energy value of a raw material or complete feed can be expressed using different energy evaluation systems. Net energy (NE) in pigs refers to the amount of energy available for maintenance and production after accounting for energy losses during digestion, metabolism, and heat production. It is a crucial concept in swine nutrition as it provides a more accurate measure of the energy value of feed ingredients compared to other systems like digestible energy (DE) and metabolizable energy (ME). Diets formulated using NE are lower in crude protein than those using DE or ME because the heat lost during catabolism and excretion of excess nitrogen is considered in the NE system.

Effect of energy

Energy is derived from three nutrients: lipids (fats and oils), carbohydrates, and proteins. Using NE values instead of DE or ME values can lead to changes in ingredient ranking when formulating diets. For example:

• Ingredients high in fat or starch may be undervalued in DE systems but receive appropriate recognition in NE evaluations.
• Conversely, protein-rich or fibrous ingredients may be favored in DE systems.

Table 1: Energy values (kcal/kg) of nutrients

Nutrient	Energy	Starch	Protein	Fat
Gross energy	GE	4,486 (100)	5,489 (122)	9,283 (207)
Digestible energy	DE	4,176 (100)	4,916 (118)	8,424 (202)
Metabolizable energy	ME	4,176 (100)	4,295 (103)	8,424 (202)
Net energy	NE	3,436 (100)	2,434 (71)	7,517 (219)
Heat production (kcal/kg)		740	1,861	907
Heat production (% of NE)		22%	76%	12%

Calculation of net energy

Net energy (kcal/kg dry matter) is calculated as:
= 2,577 x digestible crude protein
+ 8,615 x digestible crude fat
+ 3,269 x ileal digestible starch
+ 2,959 x ileal digestible sugars
+ 2,291x fermentable carbohydrates

Factors affecting nutrient digestibility

This raises the obvious question, ‘What is the nutrient digestibility of your raw materials?’ Dr. Fledderus considered several factors that affect nutrient digestibility and, therefore, NE values, including

• Age: as pigs grow, their digestive systems mature, leading to improved nutrient digestibility. Younger pigs typically have lower digestibility rates due to an underdeveloped gastrointestinal tract. Older pigs typically exhibit higher digestibility, especially for fibrous diets, as their digestive systems become more efficient at breaking down complex nutrients.
• Physiological stage: the digestibility of diets can vary between pregnant and lactating sows. Digestibility is generally higher for gestating sows; lactating sows may have slightly lower digestibility due to higher feed intake. Also, lactating sows do not consume enough feed to meet their energy needs, leading to body tissue mobilization and weight loss.
• Feed intake and number of meals per day: Increased feed intake and more frequent meals can enhance nutrient digestibility. Regular feeding helps maintain gut motility and reduces the risk of digestive disturbances. Studies indicate that pigs fed multiple smaller meals exhibit better nutrient absorption than those fed larger meals less frequently.
• Use of antibiotics and feed additives: including exogenous enzymes and other additives can improve nutrient breakdown and overall digestibility of complex feed components, further influencing ingredient rankings within different energy evaluation systems. Antibiotics can lead to dysbiosis, negatively impacting overall gut health and digestion.
• Feed processing: gelatinized starch is more easily broken down by digestive enzymes, resulting in higher and faster digestibility compared to raw or unprocessed starch. This increased digestibility leads to a greater proportion of energy being absorbed in the small intestine, contributing positively to the NE value of the feed. As the particle size of feed ingredients decreases, the NE increases. While smaller particles generally improve digestibility, excessively fine grinding can lead to adverse effects such as increased risk of gastric ulcers in pigs.
• Intestinal health: a healthy gut is crucial for optimal nutrient absorption. Factors such as the presence of beneficial microbiota and the integrity of the intestinal barrier play significant roles in nutrient digestibility. Conditions like inflammation or dysbiosis can impair nutrient absorption and decrease overall performance.

NE system shows better the “true” energy of the diet

Dr. Fledderus concluded that the NE system offers a closer estimate of pigs’ “true” energy available for maintenance and production (growth, lactation, etc.). This leads to better ingredient rankings, reduced crude protein levels, which decreases nitrogen excretion, and enhanced nutrient utilization, contributing to more sustainable pig production practices. This aligns with increasing demands for environmentally responsible farming methods.

EW Nutrition’s Swine Academy took place in Ho Chi Minh City and Bangkok in October 2024. Dr. Jan Fledderus, Product Manager and Consultant at the S&C team at Schothorst Feed Research, one of the founders of the Advanced Feed Package and with a strong focus on continuously improving the price/quality ratio of the diets for a competitive pig sector, was a reputable guest speaker in these events.

Conference Report

“A good start is half the battle” can be said if we talk about piglet rearing. For this promising start, piglets must eat solid feed as soon as possible to be prepared for weaning. Dr. Jan Fledderus, Product Manager and Consultant at the S&C team at Schothorst Feed Research, shows some nutritional measures that can be taken to keep piglets healthy and facilitate the critical phase of weaning.

Higher number of low-birth-weight pigs in larger litters

Litter size affects piglet quality. Larger litter sizes from hyperprolific sows often result in higher within-litter variation in birth weights. This variability can lead to a higher proportion of low-birth-weight piglets, which are more susceptible to health issues and have lower survival rates. Additionally, low birthweight pigs have an increased risk of mortality, and an improvement in birth weight from 1kg to 1.8 kg can result in 10 kg more body weight at slaughter.

Implementing management practices for low-birth-weight pigs, such as split suckling, can significantly enhance nutrient intake, support immune function, and ultimately contribute to better survival rates and overall health for these vulnerable piglets.

Weaning age determines intake of creep feed

Pigs that consume creep feed before weaning restart faster to eat, have a higher feed intake, and less diarrhea after weaning. For instance, in a field trial, pigs that consumed feed 10 days before weaning had a 62% incidence of diarrhea, whereas in pigs that consumed feed only 3 days pre-weaning, diarrhea incidence increased to 86%.

“As age is the most critical factor for a high percentage of pigs eating before weaning, there is a trend in the EU to increase the weaning age, where some farmers go to 35 days,” remarked Dr. Fledderus.

Furthermore, weaning age is positively correlated with weaning weight. Every day older at weaning improves post-weaning performance and reduces health problems.

Feed management

Creep feed for 7-10 days pre-weaning is essential, not to increase total feed intake, but to train the piglet to eat solid feed to avoid the ‘post-weaning dip.’ After about 15 days of age, piglets can consume more than is provided by milk alone. Dr. Fledderus strongly recommended creep feeding for at least one week before weaning. “Consuming feed before weaning will result in fewer problems with post-weaning diarrhea,” he said.

In addition to creep feeding, a transition diet, from 7 days pre- and 7 days post-weaning, is advised. The composition or form of the transition diet should not be changed.

The key objective of post-weaning diets is to achieve a pH of 2-3.5 in the distal stomach. Pepsin, the primary enzyme responsible for protein digestion, is activated at a pH of around 2.0. Its activity declines significantly at a pH above 3.5, which can lead to poor protein digestion and nutrient absorption.

Fiber as a functional ingredient

Fiber was previously considered a nutritional burden or diluent, but now it is regarded as a functional ingredient. Including dietary fiber, mainly inert fiber such as rice or wheat brans, can increase the retention time of the digesta in the stomach. This extended retention allows for more prolonged contact between digestive enzymes and nutrients, facilitating improved digestion and absorption of proteins and other nutrients. Not only is pH reduced, but because more proteins are hydrolyzed to peptides, there is less undigested protein as a substrate for the growth of pathogenic bacteria and the production of toxic metabolites in the hindgut.

“Size of fiber particles also matters,” said Dr. Fledderus. Coarse wheat bran particles (1,088 μm) have been shown to be more effective than finer particles (445 μm) in reducing E. coli levels in the gut. The larger particle size helps prevent E. coli from binding to the intestinal epithelium, allowing these bacteria to be excreted rather than colonizing the gut.

The understanding of dietary fiber’s role in pig nutrition has evolved, with recent findings indicating that fiber can actually increase feed intake in piglets, contrary to earlier beliefs that it might decrease intake. High-fiber diets often increase feed intake as pigs compensate for lower energy density. This can help maintain growth rates when formulated correctly.

EW Nutrition’s Swine Academy took place in Ho Chi Minh City and Bangkok in October 2024. Dr. Jan Fledderus, Product Manager and Consultant at the S&C team at Schothorst Feed Research, one of the founders of the Advanced Feed Package and with a strong focus on continuously improving the price/quality ratio of the diets for a competitive pig sector, was a reputable guest speaker in these events.

Conference Report

During lactation, the focus should be on maximizing milk production to promote litter growth while reducing weight loss of the sow, stated Dr. Jan Fledderus during the recent EW Nutrition Swine Academies in Ho Chi Minh City and Bangkok. A high body weight loss during lactation negatively affects the sow’s performance in the next cycle and impairs her longevity.

Milk production – ‘push’ or ‘pull’?

“Is a sow’s milk production driven by “push” – the sow is primarily responsible for milk production, or “pull” – suckling stimulates the sow to produce milk?” asked Dr. Jan Fledderus at the beginning of his presentation. The answer is that it is primarily a pull mechanism: piglets that suckle effectively and frequently can activate all compartments of the udder, leading to increased milk production. Therefore, the focus should be optimizing piglet suckling behavior (pull) to enhance milk production. This highlights the importance of piglet vitality and access to the udder in maximizing milk yield.”

Modern sows are lean

Modern sows have been genetically selected for increased growth rates and leanness, which alters their body composition. This makes traditional body condition scoring (BCS) methods, which rely on subjective visual assessment and palpation of backfat thickness, less effective. This may not accurately represent a sow’s true condition, especially in leaner breeds where muscle mass is more prominent than fat. Technology, such as ultrasound measurements of backfat and loin muscle depth, provide more accurate assessments of body condition and can help quantify metabolic reserves more effectively than visual scoring.

Due to their increased lean body mass, we must consider adjusted requirements for amino acids, energy, digestible phosphorus, and calcium. Their dietary crude protein and amino acid requirements have increased drastically.

Importance of high feed intake for milk production

Sows typically catabolize body fat and protein to meet the demands of milk production. Adequate feed intake helps reduce this catabolism, allowing sows to maintain body condition while supporting their piglets’ nutritional needs.

Feeding about 2.5kg on the day of farrowing ensures that sows receive adequate energy to support the farrowing process and subsequent milk production. Sows that are well-fed before farrowing tend to have shorter farrowing durations due to better energy availability during labor.

A short interval between the last feed and the onset of farrowing (3 hours) has been shown to significantly reduce the probability of both assisted farrowing and stillbirths without increasing the risk of constipation. To enhance total feed intake, feeding lactating sows at least three times a day is helpful.

Dr. Fledderus recommended a gradual increase in feed intake during lactation, then from day 12 of lactation to weaning, feeding 1% of sow’s bodyweight at farrowing + 0.5 kg/piglet. For example, for a 220kg sow with 12 piglets:

(220 kg x 0.01) + (12 x 0.5 kg) = 2.2 +6 = 8.2 kg total daily feed intake

Energy source – starch versus fat

The choice between starch and fat as an energy source in sow diets has substantial implications for body composition and milk production.

Starch digestion leads to glucose release, stimulating insulin secretion from the pancreas. Insulin is essential for glucose uptake and utilization by tissues. Enhanced insulin response can help manage body weight loss by promoting nutrient storage and reducing the mobilization of the sow’s body reserves.

Sows fed diets with a higher fat supplementation had an increased milk fat, which is crucial for the growth and development of piglets.

Table 1: Effect of energy source (starch vs. fat) on sows’ body composition and milk yield (Schothorst Feed Research)

	Diet 1	Diet 2	Diet 3
Energy value (kcal/kg)	2,290	2,290	2,290
Starch (g/kg)	300	340	380
Fat (g/kg)	80	68	55
Feed intake (kg/day)	6.7	6.7	6.8
Weight loss (kg)	15	11	10
Weight loss (kg)	3.1	2.7	2.3
Milk fat (%)	7.5	7.2	7.0
Milk fat (%)	260	280	270

Heat stress impacts performance

The optimum temperature for lactating sows is 18°C. A meta-analysis concluded that each 1°C above the thermal comfort range (from 15° to 25°C) leads to a decrease in sows’ feed intake and milk production and weaning weight of piglets, as shown below.

To mitigate the effects of heat stress, which reduces feed intake, it is beneficial to schedule feeding during cooler times of the day. This strategy helps maintain appetite and ensures that sows consume sufficient nutrients for milk production. Continuous access to cool, clean water can also enhance feed consumption.

Pigs produce much heat, which must be “excreted”. Increased respiratory rate (>50 breaths/minute) has been shown to be an efficient parameter for evaluating the intensity of heat stress in lactating sows.

When sows resort to panting as a mechanism to dissipate heat, this rapid breathing increases the loss of carbon dioxide, resulting in respiratory alkalosis. To prevent a rise in blood pH level, HCO₃ is excreted via urine, and positively charged minerals (calcium, phosphorous, magnesium, and potassium) are needed to facilitate this excretion. However, these minerals are crucial for various physiological functions. As their loss can lead to deficiencies that affect overall health and productivity, this mineral loss must be compensated for.

Implications for management

Implementing effective nutritional strategies together with robust management practices is crucial for maximizing the health and productivity of sows. The priority is to stimulate the sow to eat more. This not only enhances milk production and litter growth but also supports the overall well-being of the sow. Regularly assessing sow performance metrics – such as body condition score, feed intake, and litter growth – can help identify areas for improvement in nutritional management.

EW Nutrition’s Swine Academy took place in Ho Chi Minh City and Bangkok in October 2024. Dr. Jan Fledderus, Product Manager and Consultant at the S&C team at Schothorst Feed Research, with a strong focus on continuously improving the price/quality ratio of the diets for a competitive pig sector and one of the founders of the Advanced Feed Package, was a reputable guest speaker in these events.

by Ajay Bhoyar, Global Technical Manager, EW Nutrition

Gut health is critical for profitable poultry production, as the gastrointestinal tract (GIT) plays a dual role in nutrient digestion and absorption while serving as a crucial defense against pathogens. A healthy gut enables efficient feed conversion, robust immune function, and resilience against diseases, reducing reliance on preventive and therapeutic antibiotics. Optimum gut health has become increasingly important in poultry production to combat antimicrobial resistance (AMR), a pressing global challenge threatening animal agriculture and public health.

AMR arises when bacteria develop antibiotic resistance, often due to overuse or misuse in human and animal settings. Predictive models suggest that by 2050, AMR could result in 10 million annual deaths and a 2.0%–3.5% reduction in global gross domestic production, amounting to economic losses between 60 and 100 trillion USD. In poultry, AMR compromises flock health, leading to higher mortality, reduced growth performance, and elevated treatment costs, directly impacting profitability. Additionally, resistant pathogens increase the risk of zoonotic disease transfer, posing serious food safety concerns.

Stricter regulations and rising consumer demand for antibiotic-free poultry products drive a shift toward sustainable, antibiotic-free production systems. However, A lack of understanding about strategies to replace AMU and their effectiveness under field conditions hampers change in farming practices (Afonso et al., 2024). Addressing AMR requires a holistic approach, encompassing enhanced biosecurity, innovative health-promoting strategies, and sustainable management practices. This paper explores practical dietary interventions to support poultry gut health while reducing dependency on antimicrobials, offering solutions for the long-term sustainability of poultry production.

Gut Mediated Immunity in Chickens

The gut is a critical component of the immune system, as it is the first line of defense against pathogens that enter the body through the digestive system. Chickens have a specialized immune system in the gut, known as gut-associated lymphoid tissue (GALT), which helps to identify and respond to potential pathogens. The GALT includes Peyer’s patches, clusters of immune cells in the gut wall, and the gut-associated lymphocytes (GALs) found throughout the gut. These immune cells recognize and respond to pathogens that enter the gut.

The gut-mediated immune response in chickens involves several mechanisms, including activating immune cells, producing antibodies, and releasing inflammatory mediators. GALT and GALs play a crucial role in this response by identifying and responding to pathogens and activating other immune cells to help fight off the infection.

The gut microbiome is a diverse community of microorganisms that live in the gut. These microorganisms can significantly impact the immune response. Certain beneficial bacteria, for example, can help stimulate the immune response and protect the gut from pathogens.

Overall, the gut microbiome, GALT, and GALs work together to create an environment hostile to pathogens while supporting the growth and health of beneficial microorganisms.

Key Factors Affecting Poultry Gut Health

The key factors affecting broiler gut health can be summarized as follows:

1. Early gut development: Gut-associated immunity responds to early feeding and dietary nutrients and is critical for protecting against exogenous organisms during the first week of life post-hatch.
2. Feed and Water Quality: The form, type, and quality of feed provided to broilers can significantly impact their gut health. Consistently available cool and hygienic drinking water is crucial for optimum production performance.
3. Stressors: Stressful conditions, such as high environmental temperatures or poor ventilation, can lead to an imbalance in the gut microbiome and an increased risk of disease.
4. Infections and medications: Exposure to pathogens or other harmful bacteria can disrupt the gut microbiome and lead to gut health issues. A robust immune system is important for maintaining gut health, as it helps to prevent the overgrowth of harmful bacteria and promote the growth of beneficial bacteria.
5. Biosecurity: Keeping the poultry environment clean and free of pathogens is crucial for maintaining gut health, as bacteria and other pathogens can quickly spread and disrupt the gut microbiome.
6. Management practices: Best practices, including proper litter management, can help maintain gut health and prevent gut-related issues.

Dietary Interventions for Optimum Gut Health

Gut health means the absence of gastrointestinal disease, the effective digestion and absorption of feed, and a normal and well-established microbiota (Bischoff, 2011). Various dietary measures can be taken to support the healthy functioning of the GIT and host defense. Water and feed safety and quality, feeding management, the form the feed is provided in (e.g., pellets), the composition of the diet, and the use of various feed additives are all tools that can be used to support health (Smits et al., 2021).

Various gut health-supporting feed additives, including organic acids, probiotics, prebiotics, phytochemicals/essential oils, etc., in combination or alone, have been explored as an alternative to antimicrobials in animal production. There were differences in the impacts of the strategies between and within species; this highlights the absence of a ‘one-size-fits-all’ solution. Nevertheless, some options seem more promising than others, as their impacts were consistently equivalent or positive when compared with animal performance using antimicrobials (Afonso et al., 2024). Including insoluble fibers, toxin binders, exogenous enzymes, and antioxidants in the feed formulations also play a crucial role in gut health optimization, which goes beyond their primary functions to combat AMR challenges.

Fig. 1: Multifactorial approach to gut health management in reduced antimicrobial use

Organic Acids

The digestive process extensively includes microbial fermentation, and as a result, organic acids are commonly produced by beneficial bacteria in the crop, intestines, and ceca (Huyghebaert et al., 2010). Organic acids’ inclusion in the poultry diet can improve growth performance due to improved gut health, increased endogenous digestive enzyme secretion and activity, and nutrient digestibility. Butyrate is highly bioactive in GIT. It increases the proliferation of enterocytes, promotes mucus secretion, and may have anti-inflammatory properties (Bedford and Gong, 2018; Canani et al., 2011; Hamer et al., 2008). These effects suggest that it supports mucosal barrier function. Butyrate is becoming a commonly used ingredient in diets to promote GIT health.

Including organic acids in the feed can decontaminate feed and potentially reduce enteric pathogens in poultry. Alternately, the formaldehyde treatment of feed is highly effective at a relatively low cost (Jones, 2011; Wales, Allen, and Davies, 2010).

Organic acids like formic and citric acid are also used in poultry drinking water to lower the microbial count by lowering the water’s pH and preventing/removing biofilms in the water lines. By ensuring feed and water hygiene, producers can minimize pathogen exposure, enhance bird health, and significantly reduce their reliance on antibiotics.

Probiotics, Postbiotics, Prebiotics and Synbiotics

Probiotics and prebiotics have drawn considerable attention to optimizing gut health in animal feeds. Probiotic supplementation could have the following effects: (1) modification of the intestinal microbiota, (2) stimulation of the immune system, (3) reduction in inflammatory reactions, (4) prevention of pathogen colonization, (5) enhancement of growth performance, (6) alteration of the ileal digestibility and total tract apparent digestibility coefficient, and (7) decrease in ammonia and urea excretion (Jha et al., 2020). Certain Lactobacilli or Enterococci species may be used with newly hatched or newborn animals; single or multi-strain starter cultures can be used to steer the initial microbiota in a desired direction (Liao and Nyachoti, 2017). Apart from using probiotics in feed and drinking water, probiotic preparations can be sprayed on day-old chicks in the hatchery or immediately after placement in the brooding house. This way, the probiotic strains/beneficial bacteria gain access to the gut at the earliest possible time (early seeding). Postbiotics are bioactive compounds produced by probiotics during fermentation, such as short-chain fatty acids, peptides, and bacterial cell wall components. Unlike live probiotics, postbiotics are stable, safer, and provide consistent health benefits.

Prebiotics like mannan-oligosaccharides (MOS), inulin, and its hydrolysate (fructo-oligosaccharides: FOS) play an important role in modulating intestinal microflora and potential immune response. Prebiotics reduce pathogen colonization in poultry and promote selective stimulation of beneficial bacterial species. Synbiotics are a combination of probiotics and prebiotics. This synergistic approach offers dual benefits by promoting the growth of beneficial bacteria and directly combating pathogens.

Dietary Fibers (DF)

The water-insoluble fibers are regarded as functional nutrients because of their ability to escape digestion and modulate nutrient digestion. A moderate level of insoluble fiber in poultry diets may increase chyme retention time in the upper part of the GIT, stimulating gizzard development and endogenous enzyme production, improving the digestibility of starch, lipids, and other dietary components (Mateos et al., 2012). The insoluble DF, when used in amounts between 3–5% in the diet, could have beneficial effects on intestinal development and nutrient digestibility.

Dietary fibers influence the development of the gizzard in poultry birds. A well-developed gizzard is a must for good gut health. Jiménez-Moreno & Mateos (2012) noted that coarse fiber particles are selectively retained in the gizzard, ensuring a complete grinding and a well-regulated feed flow. Secretion of digestive juices regulates GIT motility and feed intake. Including insoluble fibers in adequate amounts improves the gizzard function and stimulates HCl production in the proventriculus, thus helping control gut pathogens.

Toxin Risk Management

Mycotoxins may have a detrimental impact on the mucosal barrier function in animals (Akbari et al., 2017; Antonissen et al., 2015; Basso, Gomes and Bracarense, 2013; Pierron, Alassane-Kpembi and Oswald, 2016). Mycotoxins like Aflatoxin B1, Ochratoxin A, and deoxynivalenol (DON) not only suppress immune responses but also induce inflammation and even increase susceptibility to pathogens (Yuhang et al., 2023). To avoid intestinal health problems, poultry producers need to emphasize avoiding levels of mycotoxins in feedstuffs and rancid fats that exceed recommended limits (Murugesan et al., 2015; Grenier and Applegate, 2013).

Bacterial lipopolysaccharides (LPS), also known as endotoxins, are the main components of the outer membrane of all Gram-negative bacteria and are essential for their survival. In stress situations, the intestinal barrier function is impaired, allowing the passage of endotoxins into the bloodstream. When the immune system detects LPS, inflammation sets in and results in adverse changes in gut epithelial structure and functionality. Dietary Intervention to bind these endotoxins in the GIT can help mitigate the negative impact of LPS on animals. Given this, toxin risk management with an appropriate binding agent able to control both mycotoxins and endotoxins appears to be a promising strategy for reducing their adverse effects. Further, adding antioxidants and mycotoxin binders to feed can reduce the effects of mycotoxins and peroxides and is more necessary in ABF programs (Yegani and Korver, 2008).

Essential oils/Phytomolecules

Essential oils (EOs) are important aromatic components of herbs and spices and are used as natural alternatives for replacing antibiotic growth promoters (AGPs) in poultry feed. The beneficial effects of EOs include appetite stimulation, improvement of enzyme secretion related to food digestion, and immune response activation (Krishan and Narang, 2014)

Essential oils (EOs), raw extracts from plants (flowers, leaves, roots, fruit, etc.), are an unpurified mix of different phytomolecules. The raw extract from Oregano is a mix of various phytomolecules (Terpenoids) like carvacrol, thymol and p-cymene. Whereas the phytomolecules are active ingredients of essential oils or other plant materials. Phytomolecule is clearly defined as one active compound.

These botanicals have received increased attention as possible growth performance enhancers for animals in the last decade via their beneficial influence on lipid metabolism, and antimicrobial and antioxidant properties (Botsoglou et al., 2002), ability to stimulate digestion (Hernandez et al., 2004), immune enhancing activity, and anti-inflammatory potential (Acamovic and Brooker, 2005). Many studies have been reported on supplementing poultry diets with some essential oils that enhanced weight gain, improved carcass quality, and reduced mortality rates (Williams and Losa, 2001). The use of some specific EO blends has been shown to have efficacy towards reducing the colonization and proliferation of Clostridium perfringens and controlling coccidia infection and, consequently, may help to reduce necrotic enteritis (Guo et al., 2004; Mitsch et al., 2004; Oviedo-Rondón et al., 2005, 2006a, 2010).

Antimicrobial properties of phytomolecules hinder the growth of potential pathogens. Thymol, eugenol, and carvacrol are structurally similar and have been proven to exert synergistic or additive antimicrobial effects when combined at lower concentrations (Bassolé and Juliani, 2012). In in-vivo studies, essential oils used either individually or in combination have shown clear growth inhibition of Clostridium perfringens and E. coli in the hindgut and ameliorated intestinal lesions and weight loss than the challenged control birds (Jamroz et al., 2006; Jerzsele et al., 2012; Mitsch et al., 2004). One well-known mechanism of antibacterial activity is linked to their hydrophobicity, which disrupts the permeability of cell membranes and cell homeostasis with the consequence of loss of cellular components, influx of other substances, or even cell death (Brenes and Roura, 2010; Solórzano-Santos and Miranda-Novales, 2012; Windisch et al., 2008; O’Bryan et al., 2015).

Apart from use in feed, the liquid phytomolecules preparations for drinking water use can prove to be beneficial in preventing and controlling losses during challenging periods of bird’s life (feed change, handling, environmental stress, etc.).  Liquid preparations can potentially reduce morbidity and mortality in poultry houses and thus the use of therapeutic antibiotics. Barrios et al. (2021) suggested that commercial blends of phytomolecule preparations may ameliorate the impact of Necrotic Enteritis on broilers. Further, they hypothesized that the effects of liquid preparation via drinking water were particularly important in improving overall mortality.

In modern, intensive poultry production, the imminent threat of resistant Eimeria looms large, posing a significant challenge to the sustainability of broiler operations. Eimeria spp., capable of developing resistance to traditional anticoccidial drugs, has become a pressing global issue for poultry operators. The resistance of Eimeria to traditional drugs, coupled with concerns over drug residue, has necessitated a shift towards natural, safe, and effective alternatives. It was found that if a drug to which the parasite has developed resistance is withdrawn from use for some time or combined with another effective drug, the sensitivity to that drug may return (Chapman, 1997).

Several phytogenic compounds, including saponins, tannins, essential oils, flavonoids, alkaloids, and lectins, have been the subject of rigorous study for their anticoccidial properties. Among these, saponins and tannins in specific plants have emerged as powerful tools in the fight against these resilient protozoa. Botanicals and natural identical compounds are well renowned for their antimicrobial and antiparasitic activity so that they can represent a valuable tool against Eimeria (Cobaxin-Cardenas, 2016). The mechanisms of action of these molecules include degradation of the cell wall, cytoplasm damage, ion loss with reduction of proton motive force, and induction of oxidative stress, which leads to inhibition of invasion and impairment of Eimeria spp. development (Abbas et al., 2012; Nazzaro et al., 2013). Natural anticoccidial products may provide a novel approach to controlling coccidiosis while meeting the urgent need for control due to the increasing emergence of drug-resistant parasite strains in commercial poultry production (Allen and Fetterer, 2002).

Role of Feed Enzymes Beyond Feed Cost Reduction

Feed enzymes have traditionally been associated with improving feed efficiency and reducing feed costs by enhancing nutrient digestibility. However, their role can extend well beyond economic benefits, profoundly impacting gut health and supporting reduced antimicrobial use in poultry production. Exogenous enzymes reduce microbial proliferation by reducing the undigestible components of feed, the viscosity of digesta, and the irritation to the gut mucosa that causes inflammation. Enzymes also generate metabolites that promote microbial diversity which help to maintain gut ecosystems that are more stable and more likely to inhibit pathogen proliferation (Bedford, 1995; Kiarie et al., 2013).

High dietary levels of non-starch polysaccharides (NSPs) can increase the viscosity of digesta. This leads to an increase in the retention time of the digesta, slows down the nutrient digestion and absorption rate, and may lead to an undesired increase in bacterial activity in the small intestine (Langhout et al., 2000; Smits et al., 1997). Further the mucosal barrier function may also be adversely affected. To solve this problem, exogenous enzymes, such as arabinoxylanase and/ or ß-glucanase, are included in feed to degrade viscous fibre structures (Bedford, 2000). The use of xylanase and ß-glucanase may also cause oligosaccharides and sugars to be released, of which certain, for example, arabinoxylan oligosaccharides, may have prebiotic properties (De Maesschalck et al., 2015; Niewold et al., 2012).

New generation xylanases coming from family GH-10 are known to effectively breakdown both soluble and insoluble arabinoxylans into a good mixture of smaller fractions of arabino-xylo-oligosaccharides (AXOS) and xylo-oligosaccharides (XOS), which exert a prebiotic effect in the GIT. Awati et.al. (2023) observed that a novel GH10 xylanase contributed to positive microbial shift and mitigated the anti-nutritional gut-damaging effects of higher fiber content in the feed. With a substantial understanding of the mode of action and technological development in enzyme technology, nutritionists can reliably consider new-generation xylanases for gut health optimization in their antibiotic reduction strategy.

 

Conclusions

The challenge of mitigating antimicrobial resistance (AMR) in poultry production necessitates a multidimensional approach, with gut health at its core. Dietary interventions, such as organic acids, probiotics, prebiotics, phytomolecules, toxin binders, and feed enzymes, promote gut resilience, enhance immune responses, and reduce reliance on antimicrobials. These strategies not only support the health and productivity of poultry but also address critical global issues of AMR and food safety.

While no single solution fits all circumstances, integrating these dietary tools with robust biosecurity measures, sound management practices, and continued research on species-specific and field-applicable strategies can pave the way for sustainable, antibiotic-free poultry production. The transition to such systems aligns with regulatory requirements and consumer expectations while contributing to global efforts against AMR.

Ultimately, embracing holistic and innovative dietary strategies ensures a resilient gastrointestinal environment, safeguarding poultry health and productivity while protecting public health and environmental sustainability for future generations.

 

References: The references can be made available upon request to the author.