Mycotoxins in poultry – External signs can give a hint

Part 3: Bone disorders and foot pad lesions

By Dr. Inge Heinzl, Editor, and Marisabel Caballero, Global Technical Manager Poultry

 

Bone health is essential for animals and humans. Besides giving structural support, allowing movement, and protecting vital organs, the bones release hormones that are crucial for mineral homeostasis and acid balance and serve as reservoirs of energy and minerals (Guntur & Rosen, 2012; Rath, N.C. & Durairaj, 2022; Suchacki et al., 2017).

Bone disorders and foot pad lesions are considerable challenges in poultry production, especially for fast-growing birds with high final weights. Due to pain, the animals do not move, and dominant, healthy birds may restrict lame birds’ access to feed and water. In consequence, these birds are often culled. Moreover, processing these birds is problematic, and often, they must be discarded or downgraded.

Foot pad lesions, another common issue in poultry production, can also have significant economic implications. On the one hand, pain restricts birds from eating and drinking and reduces weight gain. On the other hand, for many producers, chicken feet constitute a substantial part of the economic value of the bird; therefore, discarding them represents a significant financial loss. Additionally, to push poultry production in the right direction concerning animal health and welfare, a foot pad scoring system at the processing plant is in place in European countries.

Mycotoxins affect bones in different ways

Mycotoxins, depending on their target organs, can have diverse effects on the skeleton of birds. For example, mycotoxins that target the liver can disrupt calcium metabolism, which in turn affects the mineralization of the bones (rickets) and the impairment of chondrocytes can slow down bone growth (e.g., tibial dyschondroplasia). When the kidneys are impacted, urate clearance decreases, plasma uric acid consequently increases, and urate crystals form in the synovial fluid and tendon sheaths of various joints, particularly the hock joints. These examples highlight the complex and varied ways mycotoxins can impact poultry bone health.

Inadequate bone mineralization and strength – Rickets and layer cage fatigue

Sufficient bone mineralization is essential for the stability of the skeleton. Calcium (Ca), Vitamin D, and Phosphorous (P) deficiency leads to inadequate mineralization, weakens the bone, and can cause soft and bent bones or, in the case of layers, cage fatigue – a collapse of the spinal bone- and paralysis. Inadequate bone mineralization can be caused in different ways, among them:

  1. Decrease in the availability of the nutrients necessary for mineralization. This can occur if the digestibility of these nutrients deteriorates
  2. Impact on the Ca/P ratio—A ratio of 1 – 2:1 is vital for adequate bone development (Loughrill et al., 2016). Mycotoxins can alter absorption and transporters for one or both elements, altering their ratio.
  3. Impact on the Vitamin D receptor, affecting its expression or the transporters for Ca and P.

Aflatoxins can impair bone mineralization by different modes of action. An important one is the impairment of the digestibility of Ca and P: Kermanshahi et al. (2007) fed broilers diets with high levels of aflatoxins (0.8 to 1.2 mg AFB1/kg feed) for three weeks, which resulted in a significant reduction of Ca and P digestibility. Other researchers, however, did not find an effect on Ca and P digestibility with lower aflatoxin levels:  Bai et al. (2014) feeding diets contaminated with 96 (starter) and 157 µg Aflatoxins (grower) per kg of feed to broilers and Han et al. (2008) saw no impact on cherry valley ducks with levels of 20 and 40 µg AFB1/kg diet.

Indirectly, a decrease in the availability of Ca and P due to aflatoxin-contaminated feed can be shown by blood or tibia levels of these minerals, as demonstrated by  Zhao et al. (2010): They conducted a trial with broilers, resulting in blood serum levels of Ca and P levels significantly (P<0.05) dropped with feed contaminated with 2 mg/kg of AFB1. Another trial conducted by Bai et al. (2014) showed decreased Ca in the tibia and reduced tibial break strength.

To get more information about the effect of mycotoxins on bone mineralization and the utilization of Ca, P, and Vit. D in animal organisms, Costanzo et al. (2015) challenged osteosarcoma cells with 5 and 50 ppb of aflatoxin B1. They asserted a significant down-modulation of the expression of the Vitamin D receptor. Furthermore, they assumed an interference of AFB1 with the actions of vitamin D on calcium-binding gene expression in the kidney and intestine.  Paneru et al. (2024) could confirm this downregulation of the Vit D receptor and additionally of the Ca and P transporters in broilers with levels of ≥75 ppb AFB1. They also saw a significant reduction in tibial bone ash content at AFB1 levels >230 ppb, a decreased trabecular bone mineral content and density at AFB1 520 ppb, and a reduced bone volume and tissue volume of the cortical bone of the femur at the level of 230 ppb (see Figure 1). They concluded that AFB1 levels of already 230 ppb contribute to bone health issues in broilers.

Figure
Figure 1: Increasing doses of AFB1 (<2 ppb – 560 ppb) deteriorate bone quality (Paneru, 2024): Cross-sectional images of femoral metaphysis with increasing AFB1 levels (left to right). The outer cortical bone is shown in light grey, and the inner trabecular bone in blue. Higher levels of AFB1 (T4 and T5) show a disruption of the trabecular bone pattern (less dense blue pattern with thinner and more fragmented bone strands and with wide spaces between the trabecular bone) (shown in white).

All experiments strongly suggest that aflatoxins harm bone homeostasis. Additional liver damage, oxidative stress, and impaired cellular processes can exacerbate bone health issues.

Trichothecenes also negatively impact bone mineralization. Depending on the mycotoxin, they may affect the gut, decreasing the absorption of Ca and P and probably provoking an imbalance in the Ca/P ratio.

For instance, when T-2 toxin was fed to Yangzhou goslings at 0.4, 0.6, and 0.8 mg/kg of diet, it decreased the Ca levels (halved at 0.8 mg/kg) and increased the P levels in the blood serum, so the Ca/P ratio decreased from the adequate ratio of 1 – 2 to 0.85, 0.66, and 0.59 (P<0.05) (Gu et al., 2023). The alterations of the Ca and P levels, the resulting decreasing Ca/P ratio, and an additional increase in alkaline phosphatase (ALP) suggest that T-2 toxin negatively impacts Ca absorption, increases ALP, and, therefore, disturbs calcification and bone development.

Other studies show that serum P levels decreased in broilers fed DON-contaminated feed with levels of only 2.5 mg/kg (Keçi et al., 2019). One reason for the lower P level is probably the lower dry matter intake, affecting Ca and P intake. Ca serum level is not typically reduced, which can be explained by the fact that Ca plays many critical physiological roles (e.g., nerve communication, blood coagulation, hormonal regulation), so the body keeps the blood levels by reducing bone mineralization. Another explanation is delivered by Li et al. (2020): After their trial with broilers, they stated that dietary P deficiency is more critical for bone development than Ca deficiency or Ca & P deficiency. The results of the trial conducted by Keçi et al. with DON (see above) were reduced bone mineralization, affected bone density, ash content, and ash density in the femur and tibiotarsus with a stronger impact on the tibiotarsus than on the femur.

In line with trichothecenes effects in Ca and P absorption, Ledoux et al. (1992) suppose that diarrhea caused by intake of fumonisins leads to malabsorption or maldigestion of vitamin D, calcium and phosphorus, having birds with rickets as a secondary effect.

Ochratoxin A (OTA) impairs kidney function, negatively affects vitamin D metabolism, reduces Ca absorption, and contributes to deteriorated bone strength (Devegowda and Ravikiran, 2009). Indications from Huff et al. (1980) show decreased tibia strength after feeding chickens OTA levels of 2, 4, and 8 µ/g, and Duff et al. (1987) report similar results also in turkey poults.

A further mycotoxin possibly contributing to leg weakness is cyclopiazonic acid produced by Aspergillus and Penicillium. This mycotoxin is known for leading to eggs with thin or visibly racked shells, indicating an impairment of calcium metabolism (Devegowda and Ravikiran, 2009). Tran et al. (2023) also showed this fact with multiple mycotoxins.

The co-occurrence of different mycotoxins in the feed – the standard in praxis – increases the risk of leg issues. A trial with broiler chickens conducted by Raju and Devegowda (2000) showed a bone ash-decreasing effect of AFB1 (300 µg/kg), OTA (2 mg/kg), and T-2 toxin (3 mg/kg), fed individually but an incomparable higher effect when fed in combination.

Impairment of bone growth – tibial dyschondroplasia (TD)

In TD, the development of long bones is impaired, and abnormal cartilage development occurs. It is frequent in broilers, with a higher incidence in males than females. It happens when the bone grows, as the soft cartilage tissue is not adequately replaced by hard bone tissue. Some mycotoxins have been related to this condition: According to Sokolović et al. (2008), actively dividing cells such as bone marrow are susceptible to T-2 toxin, including the tibial growth plates, which regulate chondrocyte formation, maturation, and turnover.

T-2 toxin: In a study with primary cultures of chicken tibial growth plate chondrocytes (GPCs) and three different concentrations of T-2 toxin (5, 50, and 500 nM), He et al. (2011) found that T-2 toxin decreased cell viability, alkaline phosphatase activity, and glutathione content (P < 0.05). Additionally, it increased the level of reactive oxygen species and malondialdehyde in a dose-dependent way, which could be partly recompensated by adding an antioxidant (N-acetyl-cysteine). They concluded that T-2 toxin inhibits the proliferation and differentiation of GPCs and contributes, therefore, to the development of TD, altering cellular homeostasis. Antioxidants may help to reduce these effects.

Gu et al. (2023) investigated the closely bodyweight-related shank length and the tibia development in Yangzhou goslings fed feed with six different levels (0 to 2.0 mg/kg) of T-2 toxin for 21 days. They determined a clear dose-dependent slowed tibial length and weight growth (p<0.05), as well as abnormal morphological structures in the tibial growth plate. As tibial growth and shank length are closely related to weight gain (Gu et al., 2023; Gao et al., 2010; Ukwu et al., 2014; Yu et al., 2022), their slowdown indicates lower growth performance.

Fumonisin B1 is also a potential cause of this kind of leg issue. Feeding 100 and 200 mg/kg to day-old turkey poults for 21 days led to the development of TD (Weibking et al., 1993). Possible explanations are the reduced viability of chondrocytes, as found by Chu et al. (1995) after 48 h of exposure, or the toxicity of FB1 to splenocytes and chondrocytes, which was shown in different primary cell cultures from chicken (Wu et al., 1995).

Bacterial chondronecrosis with osteomyelitis lameness (BCO) can be triggered by DON and FUM

BCO presents a highly critical health and welfare issue in broiler production worldwide, and it is estimated that 1-2 % of condemnations in birds at the marketing age result from this disease. What is the reason? Today’s fast-growing broilers are susceptible to stress. This enables pathogenic bacteria to compromise epithelial barriers, translocate from the gastrointestinal tract or the pulmonary system into the bloodstream, and colonize osteochondrotic microfractures in the growth plate of the long bone. This can lead to bone necrosis and subsequent lameness.

In their experiment with DON and FUM in broilers, Alharbi et al. (2024) showed that these mycotoxins reduce the gut’s barrier strength and trigger immunosuppressive effects. They used contaminations of 0.76, 1.04, 0.94, and 0.93 mg DON/kg of feed and 2.40, 3.40, 3.20, and 3.50 mg FUM/kg diet in the starter, grower, finisher, and withdrawal phases, respectively. The team observed lameness on day 35; the mycotoxin groups always showed a significantly (P<0.05) higher incidence of cumulative lameness.

The increase in uric acid leads to gout

In general, mycotoxins, which damage the kidneys and, therefore, impact the renal excretion of uric acid, are potentially a factor for gout appearance.

One of these mycotoxins is T-2 toxin. With the trial mentioned before (Yangzhou goslings, 21 days of exposure), Gu et al. (2023) showed that the highest dosage of the toxin (2.0 mg/kg) significantly increased uric acid in the blood (P<0.05), possibly leading to the deposit of uric acid crystals in the joints and to gout.

Huff et al. (1975) applied Ochratoxin to chicks at 0, 0.5, 1.0, 2.0, 4.0, and 8.0 µg/g of feed during the first three weeks of life. They found ochratoxin A as a severe nephrotoxin in young broilers as it caused damage to the kidneys with doses of 1.0 µg/g and higher. At 4.0 and 8.0 µg/g doses, uric acid increased by 38 and 48%, respectively (see Figure 2). Page et al. (1980) also reported increased uric acid after feeding 0.5 or 1.0 mg/kg of Ochratoxin A to adult white Leghorn chickens.

FigureFigure 2: Effect of Ochratoxin A on plasma uric acid (mg/100 ml) (according to Huff et al., 1975)

Foot pad lesions – a further hint of mycotoxicosis

Foot pad lesions often result from wet litter, originating from diarrhea due to harmed gut integrity. Frequently, mycotoxins impact the intestinal tract and create ideal conditions for the proliferation of diarrhea-causing microorganisms and, therefore, secondary infections. Some also negatively impact the immune defense system, allowing pathogens to settle down or aggravate existing bacterial or viral parasitic diseases. In general, mycotoxins affect the physical (intestinal cell proliferation, cell viability, cell apoptosis), chemical (mucins, AMPs), immunological, and microbial barriers of the gut, as reported by Gao et al. (2020). Here are some examples of the adverse effects of mycotoxins leading to intestinal disorders and diarrhea:

  • Mycotoxins can modulate intestinal epithelial integrity and the renewal and repair of epithelial cells, negatively impacting the intestinal barrier’s intrinsic components; for instance, DON can significantly reduce the transepithelial electrical resistance (TEER)(Grenier and Applegate, 2013). A higher permeability of the epithelium and a decreased absorption of dietary proteins can lead to higher protein in the digesta in the small intestine, which serves as a nutrient for pathogens including perfringens (Antonissen et al., 2014; Antonissen et al., 2015).
  • The application of Ochratoxin A (3 mg/kg) increased the number of S. typhimurium in the duodenum and ceca of White Leghorn chickens (Fukata et al., 1996). Another trial with broiler chicks at a concentration of 2 mg/kg aggravated the symptoms due to an infection by S. gallinarum (Gupta et al., 2005).
  • In a trial by Grenier et al., 2016, feed contaminated with DON (1.5 mg/kg), Fumonisin B (20 mg/kg), or both mycotoxins aggravated lesions caused by coccidia.
  • DON impacts the mucus layer composition by downregulating the expression of the gene coding for MUC2, as shown in a trial with human goblet cells (Pinton et al., 2015). The mucus layer prevents pathogenic bacteria in the intestinal lumen from contacting the intestinal epithelium (McGuckin et al., 2011).
  • Furthermore, DON and other mycotoxins decrease the populations of lactic acid-producing bacteria, indicating a shift in the microbial balance (Antonissen et al., 2016).
  • FB1 causes intestinal disturbances such as diarrhea, although it is poorly absorbed in the intestine. According to Bouhet and Oswald (2007), the main toxicological effect ascertained in vivo and in vitro is the accumulation of sphingoid bases associated with the depletion of complex sphingolipids. This negative impact on the sphingolipid biosynthesis pathway could explain other adverse effects, such as reduced intestinal epithelial cell viability and proliferation, modification of cytokine production, and impairment of intestinal physical barrier function.
  • T-2 toxin can disrupt the immune response, enhance the proliferation of coli in the gut, and increase its efflux (Zhang et al., 2022).

All these mycotoxins can cause foot pad lesions by impacting gut integrity or damaging the gut mucosa. They promote pathogenic organisms and, thus, provoke diarrhea and wet litter.

Mitigating the negative impact of mycotoxins on bones and feet is crucial for performance

Healthy bones and feet are essential for animal welfare and performance. Mycotoxins can be obstructive. Consequently, the first step to protecting your animals is to monitor their feed. If the analyses show the occurrence of mycotoxins at risky levels, proactive measures must be taken to mitigate the issues and ensure the health and productivity of your poultry.

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Wu, Weidong, Tianxing Liu, and Ronald F. Vesonder. “Comparative Cytotoxicity of Fumonisin B1 and Moniliformin in Chicken Primary Cell Cultures.” Mycopathologia 132, no. 2 (November 1995): 111–16. https://doi.org/10.1007/bf01103783.

Yu, Jun, Yu Wan, Haiming Yang, and Zhiyue Wang. “Age- and Sex-Related Changes in Body Weight, Muscle, and Tibia in Growing Chinese Domestic Geese (Anser Domesticus).” Agriculture 12, no. 4 (March 25, 2022): 463. https://doi.org/10.3390/agriculture12040463.

Zhang, Jie, Xuerun Liu, Ying Su, and Tushuai Li. “An Update on T2-Toxins: Metabolism, Immunotoxicity Mechanism and Human Assessment Exposure of Intestinal Microbiota.” Heliyon 8, no. 8 (August 2022). https://doi.org/10.1016/j.heliyon.2022.e10012.

Zhao, J., R.B. Shirley, J.D. Dibner, F. Uraizee, M. Officer, M. Kitchell, M. Vazquez-Anon, and C.D. Knight. “Comparison of Hydrated Sodium Calcium Aluminosilicate and Yeast Cell Wall on Counteracting Aflatoxicosis in Broiler Chicks.” Poultry Science 89, no. 10 (October 2010): 2147–56. https://doi.org/10.3382/ps.2009-00608.




Can phytogenics have a meaningful effect in coccidiosis control?

by Madalina Diaconu, Global Manager Gut Health, EW Nutrition

Coccidiosis, caused by Eimeria spp., is a major challenge in poultry production, leading to significant economic losses. Historically, control strategies have relied on chemical anticoccidials and ionophores. However, the emergence of drug-resistant Eimeria strains and consumer concerns about chemical residues necessitate alternative solutions. Phytogenics, especially tannins and saponins, offer promising natural solutions to be included in programs for coccidiosis control. More and more independent research highlights the potential of these natural compounds to enhance poultry health and productivity.

Efficacy of Tannins and Saponins in Coccidiosis Control

Phytogenics are plant-derived bioactive compounds known for their antimicrobial, antioxidant, and immunomodulatory properties. Among these, tannins and saponins have shown particular promise in supporting coccidiosis control.

Phytogenics
Phytogenics

The challenge: Preventing the spread of infections and mitigating subclinicial coccidiosis before it reaches this stage.

Tannins

Tannins are polyphenolic compounds found in various plants. They exhibit strong antimicrobial activity by binding to proteins and metal ions, disrupting microbial cell membranes, and inhibiting enzymatic activity.

Anticoccidial Activity: Tannins have been shown to interfere with the life cycle of Eimeria. Studies demonstrate that tannins can reduce oocyst shedding and intestinal lesion scores in infected birds (Abbas et al., 2017).

Immune Modulation: Tannins enhance immune responses by promoting the proliferation of lymphocytes and the production of antibodies, which help in the clearance of Eimeria infections (Redondo et al., 2021).

Saponins

Saponins are glycosides with surfactant properties, capable of lysing cell membranes of pathogens. They also stimulate immune responses, enhancing the host’s ability to fight infections.

Membrane Disruption: Saponins disrupt the cell membranes of Eimeria, leading to reduced parasite viability and replication (Githiori et al., 2004).

Immune Enhancement: Saponins stimulate the production of cytokines and enhance the activity of macrophages, improving the overall immune response against coccidiosis (Zhai et al., 2014).

Independent Research Evidences Phytogenics’s Role in Supporting Programs for Coccidiosis Control

Numerous studies have evaluated the efficacy of phytogenics in coccidiosis control. Here, we highlight key findings from peer-reviewed research:

Abbas et al. (2012): This study reviewed various botanicals and their effects on Eimeria species in poultry. The authors concluded that tannins and saponins significantly reduce oocyst shedding and lesion scores, comparable to conventional anticoccidials.

Allen et al. (1997): The authors investigated the use of dietary saponins in controlling Eimeria acervulina infections. The study found that saponin-treated birds exhibited lower oocyst counts and improved weight gain compared to untreated controls.

Masood et al. (2013): This study explored the role of natural antioxidants, including tannins, in controlling coccidiosis. The results indicated that tannins reduced oxidative stress and improved intestinal health, leading to better performance in broiler chickens.

Idris et al. (2017): The researchers assessed the potential of saponin-rich plant extracts against avian coccidiosis. The findings demonstrated significant reductions in oocyst output and lesion severity, highlighting the potential of saponins as effective anticoccidials.

Hailat et al. (2023): The researchers studied three phytogenic formulations against a control group with chemical drugs. The study concluded that phytogenic blends can be safely used as alternatives to the chemically synthesized drugs, either alone or in a shuttle program, for the control of poultry coccidiosis.

El-Shall et al. (2021): This review article highlights research findings on phytogenic compounds which showed preventive, therapeutic, or immuno-modulating effects against coccidiosis.

Despite initial skepticism, the growing body of evidence supports the efficacy of phytogenics in supporting coccidiosis control. Tannins and saponins, in particular, have shown significant potential in reducing parasite load, improving intestinal health, and enhancing immune responses. These natural compounds offer several advantages over traditional chemical treatments, including lower risk of resistance development and absence of harmful residues in meat products.

Challenges and Promises

While the efficacy of phytogenics is well-supported, challenges remain, especially with lower-quality products that may display variability in plant extract composition, in their standardization of doses, and in ensuring consistent quality. At the same time, these compounds are not silver bullets, and no producer should make unreasonable claims.

As far as the mode of action is concerned, the evidence is becoming clear: phytogenics, particularly tannins and saponins, are effective in mitigating gut health challenges and supporting bird performance when challenged. Their natural origin, coupled with potent antimicrobial and immunomodulatory properties, makes them suitable for sustainable poultry production. As the poultry industry seeks to reduce reliance on chemical drugs, phytogenics represent a viable and promising solution.

References

Abbas, R. Z., Iqbal, Z., Blake, D., Khan, M. N., & Saleemi, M. K. (2011). “Anticoccidial drug resistance in fowl coccidia: the state of play revisited”. World’s Poultry Science Journal, 67(2), 337-350. https://doi.org/10.1017/S004393391100033X

Allen, P. C., Danforth, H. D., & Levander, O. A. (1997). “Interaction of dietary flaxseed with coccidia infections in chickens”. Poultry Science, 76(6), 822-828. https://doi.org/10.1093/ps/76.6.822

El-Shall, N.A., El-Hack, M.E.A., et al. (2022). “Phytochemical control of poultry coccidiosis: a review”. Poultry Science, 101(1) 101542. https://doi.org/10.1016/j.psj.2021.101542

Idris, M., Abbas, R. Z., Masood, S., Rehman, T., Farooq, U., Babar, W., Hussain, R., Raza, A., & Riaz, U. (2017). “The potential of antioxidant rich essential oils against avian coccidiosis”. World’s Poultry Science Journal, 73(1), 89-104. https://doi.org/10.1017/S0043933916000787

Hailat, A.M., Abdelqader, A.M., & Gharaibeh, M.H. (2023). “Efficacy of Phyto-Genic Products to Control Field Coccidiosis in Broiler Chickens”. International Journal of Veterinary Science, 13(3), 266-272. https://doi.org/10.47278/journal.ijvs/2023.099

Masood, S., Abbas, R. Z., Iqbal, Z., Mansoor, M. K., Sindhu, Z. U. D., & Zia, M. A. (2013). “Role of natural antioxidants for the control of coccidiosis in poultry”. Pakistan Veterinary Journal, 33(4), 401-407.

Redondo, L. M., Chacana, P. A., Dominguez, J. E., & Miyakawa, M. E. (2021). “Perspectives in the use of tannins as alternative to antimicrobial growth promoter factors in poultry”. Frontiers in Microbiology, 12, 641949. https://doi.org/10.3389/fmicb.2021.641949

Zhai, H., Liu, H., Wang, S., Wu, J., & Kluenter, A. M. (2014). “Potential of essential oils for poultry and pigs”. Animal Nutrition, 2(4), 196-202. https://doi.org/10.1016/j.aninu.2016.12.004




Low Crude Protein Diets in Poultry: Understanding the Consequences

BROILER

Conference report

The concept of feeding poultry, specifically broilers and layers, with reduced crude protein (CP) diets is gaining traction among nutritionists. The economic implications of balancing amino acids currently dictate dietary CP levels. At the recent EW Nutrition Poultry Academy in Jakarta, Indonesia, Dr. Steve Leeson, Professor Emeritus at the University of Guelph, Canada, raised a crucial question: “What does ‘low CP’ really mean?” He states that it typically means a reduction of maximum 2-3% relative to current CP levels.

Low CP diets generally involve a decrease in soybean meal, compensated by higher grain content. This change increases dietary starch and decreases dietary lipid levels. To meet nutritional needs, these diets also include higher amounts of crystalline (synthetic) amino acids.

Dr. Leeson outlined the advantages and disadvantages of low CP diets. Positives include improved gut health due to reduced proteolytic bacteria, less environmental pollution, lower water intake (improving litter quality), improved sustainability indices, increased dietary net energy, and better performance during heat stress. Negatives encompass issues like lower pellet quality, altered dietary electrolyte balance, higher diet costs, reduced growth rate and feed efficiency, and increased abdominal fat deposition. There are also questions about the presumed complete utilization of crystalline amino acids, which can be as high as 25kg/MT in these diets.

Challenges with Low CP Diets

  • Protein vs. Amino Acids: Diets are typically formulated based on digestible amino acid content, though minimum CP levels remain common, to avoid reduced performance: Dr. Leeson noted that broiler diets with less than 19% CP in starter and 15% in finisher phases, and layer diets below 13% CP, often fail to deliver adequate performance, regardless of digestibly amino acid supply.
  • Utilization of Free Amino Acids: The crystalline amino acids are immediately absorbable in the small intestine, contrasting with protein-bound amino acids that are absorbed as di- and tri-peptides. Amino acids absorption dynamics and endogenous loss of amino acids are affected by (high) levels of  crystalline amino acids.
  • Non-Essential Amino Acids: The impact of reduced CP on animal performance might be related to the lower levels of presumed non-essential amino acids, e.g. glycine and serine.  This is an area for further exploration.
  • Energy Level Considerations: Dr. Leeson suggests maintaining specific ratios of digestible lysine to apparent metabolizable energy in broilers at different growth stages. The heat increment of CP is an essential factor, as it reduces net energy efficiency, possibly requiring an adjustment in amino acid to metabolizable energy ratios as poultry diets are not based on net energy values.
  • Gut Health: Lower CP levels can reduce the flow of undigested protein into the hindgut, reducing the risk of necrotic enteritis, and the production of harmful metabolites, like biogenic amines.
  • Role of Proteases: Protease use can lead to a further 2-4% reduction in dietary CP, with the response depending on the inherent protein digestibility of the diets.
  • Impacts on Pellet Quality: Due to the binding properties of protein, each 1% reduction in CP typically results in a 2% decrease in pellet durability (index).
  • Electrolyte Balance: Reduced CP can significantly lower dietary electrolyte balance, which has to be considered in feed formulation. Amongst the nutrients contributing to DEB value, Sodium and Potassium appear to be the most influential minerals to consider.

Conclusion

Dr. Leeson anticipates that low CP diets will become increasingly relevant. They have the potential to reduce environmental pollution and dependence on soybean meal, despite current challenges in reducing feed costs.

 

***

EW Nutrition’s Poultry Academy, featuring Dr. Leeson, took place in Jakarta and Manila in early September 2023. With nearly 50 years of industry experience, Dr. Leeson has made significant contributions to poultry nutrition and management, evidenced by his numerous awards and over 400 published papers.




Nutritional considerations for immunity and gut health

Chicks
Conference report 

At the recent EW Nutrition Poultry Academy in Jakarta, Indonesia, Dr Steve Leeson, Professor Emeritus, University of Guelph, Canada, opened his presentation by stating that “it is obvious that any nutrient deficiency will impact bird health, but not so obvious is that nutrition per se can positively impact immunity and health in an otherwise healthy and high-producing bird.”

Modern high-performing broilers are characterized by extremely high feed intake. This puts a lot of stress on the physiology of the entire gastrointestinal tract, but particularly so on the absorptive epithelial cells of the small intestine. Any organism requires a nutrient source for survival and reproduction. Dr Leeson asked “can we significantly reduce nutrient supply to pathogens, while sustaining bird productivity?”

He reminded the audience that no cellular function comes for free: so there is always a “cost”. A general conclusion is that 10% of nutrients can be used for immune function during disease challenge, and always get priority. Therefore, you don’t want to overstimulate the immune system, which in extreme situations leads to an inflammatory response. In his presentation, Dr Leeson considered factors determining gut health and nutritional tools which are available to support gut health.

Gut microflora

Gut pathogens impact the bird and/or the consumer. Clostridia and E. coli are the major concerns regarding bird health and productivity, whereas Salmonella and Campylobacter are major pathogens important for human health.

The chick hatches with a gut virtually devoid of microbes, so early colonizers tend to predominate quite quickly. Microbial species present on the hatching tray, during delivery and during the first few days at the farm will likely dictate early gut colonization. In some instances, the chick’s microflora may be established by the time it gets to the farm, so the probiotic faces more of a challenge to establish itself as the predominant species.

Antibiotic alternatives

Gut villi development matures at around 10-15 days of age. The broiler pre-starter diet therefore is a target for feed additives that positively impact gut structure and development.

  • Among the short chain fatty acids, butyric acid is considered the prime energy source for enterocytes and it is also necessary for the correct development of the gut-associated lymphoid tissue (GALT). Butyric acid can also be added indirectly via fermentation of judicious levels of soluble fiber to encourage optimal gut villi development. Dr Leeson added that he is a big believer in butyric acid, encouraging a good gut structure at 10 days, which can be worth about 50 kcal.
  • Exogenous enzymes should also be considered in an attempt to maximize digestion and limit the flow of nutrients to the large intestine and ceca. Protease enzymes have great potential in this regard, since they allow nutritionists to reduce dietary crude protein and hopefully reduce the supply of nitrogen that fuels proteolytic Clostridia bacteria in the large intestine and ceca.
  • Amino acids, particularly threonine, play a critical role in the maintenance of intestinal mucosal integrity and barrier function, especially for mucin synthesis, which protects enterocytes from adherence by pathogenic bacteria, and from attack by endogenous enzymes and acids.
  • Polyunsaturated fatty acids (PUFAs) – Omega-3s and especially DHA from fish oil help to reduce inflammatory response (overstimulation). Omega-3s are poorly converted to DHA by the chicken, so conventional sources such as flax are of limited application for immunity.
  • Blood plasma from pigs or cattle is a complex spray-dried mixture of proteins and amino acids, many of which are immunoglobulins that “temper” the immune system, much like PUFAs.
  • Vitamins A, D, E and C have vital roles in the normal function of the immune system and have antioxidant capacity.
  • Certain complex carbohydrates, such as ß-glucans, influence gut health due to their fermentation, leading to the production of short-chain fatty acids, such as butyrate.
  • Antioxidants – to firstly control oxidation of fats and fat-soluble vitamins in feed, and secondly to optimize birds’ cellular oxidative capacity, to prevent cell damage, therefore maintaining healthy cellular and immune function.
  • Betaine increases intracellular water retention, reducing “dehydration” of microvilli and increasing their volume/surface area.
  • Fiber – moderate levels (1-2%) of soluble (fermentable) and insoluble fiber can be beneficial to early gut development by stimulating gizzard development and endogenous enzyme production.
  • Phytogenics are becoming very common in combination with acidifiers (upper tract) and probiotics. Essential oils are becoming more mainstream the more we know about them.

Recommendations for optimizing gut health and immunity

Fast growth rate and high egg output are negatively correlated with immune response. Consequently, nutrient-dense diets are not optimal for immunity. With bacteria, it’s a numbers game – but these numbers quickly multiply. The first 7 days are important, therefore probiotics must be established early. Consider the role of targeted feed additives, such as butyrate, phytogenics, antioxidants, PUFAs etc.

Also, maximize feed particle size – the limit is usually pellet quality. Mitigate nutrient transition at any diet change. Review the supply of trace minerals, as there is a trend to lower levels of organic minerals. With all the factors that weigh into production performance, any support that can be rallied through nutrition needs to be considered.

 

***

EW Nutrition’s Poultry Academy took place in Jakarta and Manila in early September 2023. Dr. Steve Leeson, an expert in Poultry Nutrition & Production with nearly 50 years’ experience in the industry, was the distinguished keynote speaker.

Dr. Leeson had his Ph.D. in Poultry Nutrition in 1974 from the University of Nottingham. Over a span of 38 years, he was a Professor in the Department of Animal &Poultry Science at the University of Guelph, Canada. Since 2014, he has been Professor Emeritus at the same University. As an eminent author, he has more than 400 papers in refereed journals and 6 books on various aspects of Poultry Nutrition & Management. He also won the American Feed Manufacturer’s Association Nutrition Research Award (1981), the Canadian Society of Animal Science Fellowship Award (2001), and Novus Lifetime Achievement Award in Poultry Nutrition (2011).

 




Decoding the connection between stress, endotoxins, and poultry health

Poultry

By Marisabel Caballero, Global Technical Manager Poultry, EW Nutrition

Stress can be defined as any factor causing disruptions to homeostasis, which triggers a biological response to regain equilibrium. We can distinguish four major types of stressors in the poultry industry:

  • Technological: related with management events and conditions
  • Nutritional: involving nutritional disbalances, feed quality and feed management
  • Pathogenic: comprising health challenges.
  • Environmental: changes in environment conditions

In practical poultry production, multiple stress factors occur simultaneously. Their effects are also additive, leading to chronic stress. The animals are not regaining homeostasis and continuously deviate the use of resources through inflammation and the gut barrier-function, thus leading to microbiome alteration. As a consequence, welfare, health, and productivity are compromised.

What are endotoxins?

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. LPS have direct contact with the bacteria’s surroundings and function as a protection mechanism against the host’s immunological response and chemical attacks from bile salts, lysozymes, or other antimicrobial agents.

Gram-negative bacteria are part of animals’ microbiota; thus, there are always LPS in the intestine. Under optimal conditions, this does not affect the animals, because intestinal epithelial cells are not responsive to LPS when stimulated from the apical side. In stress situations, the intestinal barrier function is impaired, allowing the passage of endotoxins into the blood stream. When LPS are detected by the immune system either in the blood or in the basolateral side of the intestine, inflammation and changes in the gut epithelial structure and functionality occur.

The gut is critically affected by stress

Even when there is no direct injury to the gut, signals from the brain can modify different functions of the intestinal tract, including immunity. Stress can lead to functional disorders, as well as to inflammation and infections of the intestinal tract. Downstream signals act via the brain–gut axis, trigger the formation of reactive oxygen and nitrogen species as well as local inflammatory factors, and circulating cytokines, affecting intestinal homeostasis, microbiome, and barrier integrity.

Stress then results in cell injury, apoptosis, and compromised tight junctions. For this reason, luminal substances, including toxins and pathogens, leak into the bloodstream. Additionally, under stress, the gut microbiome shows and increment on Gram-negative bacteria (GNB). For instance, a study by Minghui Wang and collaborators (2020) found an increase of 24% in GNB and lower richness, in the cecum of pullets subjected to mild heat stress (increase in ambient temperature from 24 to 30°C).

Both these factors, barrier damage and alterations in the microbiome, facilitate the passage of endotoxins into the blood stream, which promotes systemic chronic inflammation.

What categories of stress factors trigger luminal endotoxins’ passage into the bloodstream?

Technological stress

Various management practices and events can be taken as stressors by the animals’ organism. One of the most common examples is stocking density, defined as the number of birds or the total live weight of birds in a fixed space. High levels are associated with stress and loss of performance.

A study from the Chung-Ang University in 2019 found that broilers with a stocking density of 30 birds/m2 presented two times more blood LPS than birds kept at half of this stocking density. Moreover, the body weight of the birds in the high-density group was 200g lower than the birds of the low-density group. The study concluded that high stocking density is a factor that can disrupt the intestinal barrier.

Nutritional stress

The feed supplied to production animals is designed to contribute to express their genetic potential, though some feed components are also continuous inflammatory triggers. Anti-nutritional factors, oxidized lipids, and mycotoxins induce a low-grade inflammatory response.

For instance, when mycotoxins are ingested and absorbed, they trigger stress and impair immunity in animals. Their effects start in gastrointestinal tract and extend from disrupting immunity to impairing the intestinal barrier function, prompting secondary infections. Mycotoxins can increase the risk of endotoxins in several ways:

A study conducted by EW Nutrition (Figure 1) shows an increase in intestinal lesions and blood endotoxins after a mycotoxin challenge of 200pbb of Aflatoxin B1 + 360ppb Ochratoxin in broilers at 21 days of age. The challenged birds show two times more lesions and blood endotoxins than the ones in the unchallenged control. The use of the right mitigation strategy, a product based on bentonite, yeast cell walls, and phytogenics (EW Nutrition GmbH) successfully prevented these effects as it not only mitigates mycotoxins, but also targets endotoxins in the gut.

Figure 1
Figure 1 Blood LPS and intestinal lesion score of broilers challenged with 200ppb AFB1 + 350 ppb OTA from 1 to 21 days of age without and with an anti-toxin product from EW Nutrition GmbH (adapted from Caballero et al., 2021)

Pathogenic stress

Intestinal disease induces changes in the microbiome, reducing diversity and allowing pathogens to thrive. In clinical and subclinical necrotic enteritis (NE), the intestinal populations of GNB, including Salmonella and E.coli also increases. The lesions associated with the pathogen compromise the epithelial permeability and the intestinal barrier function, resulting in translocation of bacteria and LPS (Figure 5) into the bloodstream and internal organs.

Figure 2
Figure 2 Increase in systemic LPS (vs a healthy control) after a NE challenge (adapted from Chen et al., 2015, Li et al., 2018 & Liu at al., 2018)

Environmental stress

Acute and chronic heat and cold stress increases gut permeability, by increasing intestinal oxidative stress and disrupting the expression of tight junction proteins. This results in the damage and destruction of intestinal cells, inflammation, and imbalance of the microbiota. An increased release and passage of endotoxins has been demonstrated in heat stress (Figure 3), as well as a higher expression of TLR-4 and inflammation.

Figure 3
Figure 3 Systemic LPS increase (in comparison with a non-stressed control) after different heat stress challenges in broilers: 16°C increased for 2, 5 and 10 hours (Huang et al., 2018); 9°C increased for 24 and 72 hours (Nanto-Hara et al., 2020); 10°C continuously for 3 and 10 days, and 15°C 4 hours daily for 3 and 10 days (Alhenaky et al., 2017)

 

Zhou and collaborators (2021) showed that 72 hours of low temperature treatment in young broilers increased intestinal inflammation and expression of tight junction proteins, while higher blood endotoxins indicate a disruption of the intestinal barrier. As a consequence, the stress decreased body gain and increased the feed conversion rate.

An experiment conducted by EW Nutrition GmbH with the objective of evaluating the ability of a toxin mitigation product to ameliorate heat-stress induced LPS. For the experiment, 1760 Cobb 500 pullets were divided into two groups, and each was placed in 11 pens of 80 hens, in a single house. One of the groups received feed containing 2kg/ton of the product from the first day. From week 8 to week 12, the temperature of the house was raised 10°C for 8 hours every day.

Throughout the heat stress period, blood LPS (Fig 4) was lower in the pullets receiving the product, which allowed lower inflammation, as evidenced by the lower expression of TLR4 (Fig. 5). Oxidative stress was also mitigated with the help of the combination of phytomolecules in the product, obtaining 8.5% improvement on serum total antioxidant capacity (TAC), supported by an increase in in superoxide dismutase (SOD glutathione peroxidase (GSH) and a decrease in malondialdehyde (MDH).

Fig

Figures 4-5
Figures 4 and 5 – Blood LPS and expression of toll-like receptor 4 (TLR4) in lymphocites of pullets before (wk 6) and during heat stress (wk 9 and 10). (*) indicates significant differences (P<0,05), and (‡) a tendency to be different against the control group (P<0,1).

In practice: there is no silver bullet

In commercial poultry production, a myriad stressors may occur at the same time and some factors trigger a chain of events that work to the detriment of animal health and productivity. Reducing the solution to the mitigation of LPS is a deceitfully simplistic approach. However, this should be part of a strategy to achieve better animal health and performance. In fact, EW Nutrition’s toxin mitigation product alone helped the pullets to achieve 3% improvement in body weight and 9 points lower cumulative feed conversion (Figure 6).

Figure 6
Figure 6

Keeping the animals as free of stress as possible is a true priority for poultry producers, as it promotes animal health as well as the integrity and function of the intestinal barrier. Biosecurity, good environment, nutrition and good management practices are crucial; the use of feed additives to reduce the consequences of unavoidable stress also critically supports the profitability of poultry operations.

 




Coccidiosis management without increasing antimicrobial resistance – it’s up to us

By Tingting Fan, Regional Technical Manager Poultry, EW Nutrition

Chicken coccidiosis is a common and important disease in poultry production, with an incidence of infection as high as 50-70%. The mortality rates are around 20-30% or higher in highly severe cases. In addition to losses due to mortality, producers lose money due to poor growth as well as decreased meat yield and quality. Additionally, the birds get more susceptible to secondary infections, e.g., necrotic enteritis (Moore, 2016).

The costs caused by coccidiosis in poultry are about 13 billion US $ (Blake, 2020). These costs globally divide into 1 billion costs for prophylaxis/treatment and 12 billion due to performance losses. Until now, only 5% of the prophylaxis costs have been created by natural solutions. That means that there is still a high potential to be tapped.

Natural solutions, unfortunately, are only used by a minority

For a long time, ionophores fitting the classical definition of antibiotics and chemicals were used in coccidia-fighting programs – and contributed to the development of antimicrobial resistance (Nesse et al., 2015). Nowadays, the combination with vaccination in rotation or shuttle programs has reduced this danger, but there is still potential. Meanwhile, some natural solutions are available that can be integrated into coccidiosis-fighting programs. However, producers using natural solutions are still a minority.

For thousands of years, plants have been used in human and veterinary medicine. Before the discovery of antibiotics in 1928, diseases were fought with plants. To regain the effectiveness of antibiotics, using natural solutions for prophylaxis should be once more standard, and the use of antibiotics is the treatment only for critical cases.

How does Eimeria damage broilers

The pathogenic mechanism of coccidia or Eimeria spp. is mainly the massive destruction of host intestinal cells when it reproduces, resulting in severe damage to the intestinal mucosa. On the one hand, the damaged gut wall loses its capability for effective digestion and absorption of nutrients, leading to worse feed conversion and lower weight gain.

On the other hand, this damage reduces the chicken’s immunity and paves the way for other infections, such as necrotic enteritis, and raises mortality.

Table 1:The seven most known Eimeria species in broilers and their main site of occurrence

Eimeria species Predilection site
E. tenella Ceca
E. acervulina Duodenum and prox. jejunum
E. maxima Central jejunum
E. mitis Distal jejunum and ileum
E. necatrix Central jejunum and ceca
E. brunetti Ileum, entrance of the ceca and rectum
E. praecox Duodenum and prox. jejunum

Concerning their pathogenicity, for poultry, the Eimeria species must be ordered in the following way: E. necatrix> E. tenella > E. brunetti > E. maxima > E. acervulina > Eimeria mitis, and Eimeria praecox.

Prevention is better than treatment

Thanks to its bi-layered wall with a robust structure, the oocysts of coccidia are extremely resilient. They can survive 4 to 9 months in the litter or soil and are resistant to common disinfectants. Farm personnel and visitors are also important vectors, so good biosecurity practices can reduce the number of oocysts contaminating the premises and help prevent clinical out-brakes. Coccidiosis control in poultry should focus on “prevention” rather than “treatment”, combining biosecurity practices, feed additives, and/or vaccination.

Effective hygiene on the farm is crucial

To prevent coccidia infections, one of the most critical points is hygiene. Biosecurity practices are crucial and include cleaning and disinfection of the poultry houses and their surroundings, pest control and prevention, restriction, control, and management of the entry of personnel, visitors, vehicles, and equipment, among others.

Coccidia oocysts are ubiquitous and survive for a long time, and even effective cleaning and disinfection cannot completely remove them. After a severe outbreak, it is recommended to take drastic biosecurity measures such as flame or caustic soda disinfection to prevent further spread of the disease.

When there are birds in the house, it must be paid attention that the litter is not excessively humid. Litter moisture should be maintained around 25%; turning and replacing moist litter are the best practices to follow. For keeping the litter dry, adequate ventilation and appropriate stocking density are beneficial.

To avoid unnecessary stress and gut health issues, the birds must be fed according to their requirements with high-quality feed so that the animals build up good immunity and resilience.

Coccidiosis can be controlled with effective programs

Anticoccidial drugs were the first means of preventing and controlling coccidiosis in chickens and once achieved very good results. Since Sulfaquinoxaline was found to be effective in the 1850s, about fifty other drugs have been developed for the prevention and control of coccidiosis. Generally, the anticoccidials used for years to prevent the disease can be divided into ionophores and chemicals.

Ionophores, produced as by-products of bacterial fermentation, are technically antibiotics. The great benefits of ionophores are that they kill the parasite before it can infect the bird and thus prevent damage to the host cells. Eimeria species also take a long time to develop resistance to ionophores (Chapman, 2015). Well-established ionophores are products that contain monensin, lasalocid, salinomycin, narasin, or maduramycin; the trade names are Coban/Monensin, Avatec, Coxisstac, Monteban, and Cygro.

Chemicals, these molecules, are produced by chemical synthesis. They differ from each other and ionophores as each one has a unique mode of action against coccidia. In general, they act by interfering with one or more stages of the life cycle of Eimeria, e.g., supplying fake nutrients (Amprolium, Vit. B1) to the parasite, starving them out. The active components here are nicarbazin, amprolium, zoalene, decoquinate, clopidol, robenidine and diclazuril, and the respective trade names Nicarb, Amprol, Zoamix, Deccox, Coyden, Robenz and Clinacox. Eimeria species develop resistance to these chemical molecules; therefore, they must be used carefully and with strict planning. However, cross-resistance does not develop, making them highly valuable in rotation programs.

Vaccination against coccidiosis is accepted by many farmers as a good solution to control coccidiosis in chickens. Vaccination aims to replace resistant field strains with vaccine strains, which are sensitive to anticoccidials. Currently, commercial chicken vaccines are available in natural and attenuated strains; research to obtain safer and more efficient vaccines is also ongoing.

Non-attenuated vaccines are less expensive and make for good immunity, but as they may mildly damage the intestinal epithelium, the risk of necrotic enteritis can increase. On the contrary, attenuated strains – usually “precocious” strains with shorter reproduction cycles, cause less intestinal damage and thus have a lower risk of provoking bacterial or necrotic enteritis. The immunity is like after normal infections; however, you have a controlled epidemiology, fewer coccidiosis outbreaks, and an improved uniformity of the flock.

Phytomolecules-based natural anticoccidials saponins and tannins are natural components that can also help control coccidiosis (e.g., Pretect D, EW Nutrition GmbH). These ingredients act in different ways: the tannins improve the intestinal barrier function locally and systemically. The saponins directly impact the oocysts by preventing their growth, interacting with the cholesterol in the cell membrane (triterpenoid saponin), or hindering further sporulation and causing cell death by causing pores in the cell membrane of the parasite. Altogether, Pretect D promotes the beneficial microbial population and reduces the harmful one, improves the gut barrier function, reduces mucosal inflammation, inhibits growth and replication of Eimeria, preventing their lesions, and fosters birds’ immune response against Eimeria spp.

To prove Pretect D’s effectiveness in the reduction of coccidiosis, several trials were conducted. One of the trials was carried out in Poland with 360.000 broilers in commercial conditions. The animals were divided into ten houses, and two cycles were tested. Half of the birds served as control and received Narasin and Nicarbazin in the starter and grower I diet and salinomycin in the grower II diet. The other half also were fed Narasin and Nicarbazin in the starter and grower I diet, but Pretect D @1kg/t in grower II and 0.5kg/t in the finisher diet. The results are shown in figure 1: The application of Pretect D in the grower II and finisher diet decreased the number of oocysts in the droppings more than the application of salinomycin and, therefore, reduced the spreading of coccidiosis. In addition, the performance of the broilers receiving Pretect D was nothing short of the control’s performance showing Pretect as an optimal completion in shuttle or rotation programs (see more HERE).

Figure Reduction Of Oocysts In The Droppings By Pretect DFigure 1: Reduction of oocysts in the droppings by Pretect D

Managing coccidiosis without promoting antimicrobial resistance is not easy, but feasible

Coccidiosis is a challenge aggravated by our current high level of production. Tools such as ionophores, chemicals, but also vaccines, and natural products are available to fight coccidiosis. However, due to the high probability of resistance development, these tools must be used carefully and in structured programs. The phytomolecules-based product Pretect D gives the possibility to reduce antimicrobial resistance as part of programs against coccidiosis.

References upon request




Pathogenic Enterococcus cecorum – an emerging profit killer for broiler producers

By Dr. Ajay Bhoyar, Global Technical Manager, EW Nutrition

Pathogenic Enterococcus cecorum (EC) is emerging as a significant challenge in poultry production worldwide, causing substantial losses to commercial flocks. EC has become a considerable concern for the poultry industry, not only because of its rapid spread and negative impact on broiler health but also because of its increasing antibiotic resistance. As a result, there is a growing need to explore alternative ways of controlling this bacterium. There is no silver bullet yet as a replacement for antibiotics to limit the load of E. cecorum. Maintaining optimum gut health to avoid E. cecorum leakage during the first week of the broiler’s life can control losses due to E. cecorum.

Phytogenic compounds, which are derived from plants, have gained attention in the last decades as a potential solution for controlling common gut pathogens. These natural compounds have been found to possess antimicrobial properties and can help improve gut health in broilers. In this article, we will discuss the current state of E. cecorum and explore potential strategies, including using phytogenic compounds as support in controlling economic losses due to this emerging pathogen in broiler production.

Enterococcus cecorum and its negative impact on broiler production

E. cecorum is a component of normal enterococcal microbiota in the gastrointestinal tract of poultry. These are facultatively anaerobic, gram-positive cocci. Over the past 15 years, pathogenic strains of E. cecorum have emerged as an important cause of skeletal disease in broiler and broiler breeder chickens (Broast et al., 2017; Jackson et al., 2004 and Jung et al., 2017). Along with the commensal strains of EC, the pathogenic strains also occur and can result in Enterococcal spondylitis (ES), also known as “kinky back”, a serious disease of commercial poultry production in which the bacteria translocate from the intestine to the free thoracic vertebrae and adjacent notarium or synsacrum, causing lameness, hind-limb paresis and, in 5 to 15% of cases, mortality (de Herdt et al., 2008; Martin et al., 2011; Jung and Rautenschlein, 2014). The compression of the spinal cord due to infection of the free thoracic vertebra results in the so-called “kinky back” in the skeletal phase of E. cecorum infection. Kinky back is also a common name for spondylolisthesis, a developmental spinal anomaly. EC is normally found in the gastrointestinal tract and may need the help of other factors, such as a leaky gut, to escape the gastrointestinal tract. The emergent pathogenic strains of E. cecorum have developed an array of virulence factors that allow these strains to 1) colonize the gut of birds in the early life period; 2) escape the gut niche; 3) spread systemically while evading the immune system; and 4) colonize the damaged cartilage of the free thoracic vertebra (Borst, 2023). The E. cecorum can invade internal organs and produce lesions in the pericardium, lung, liver, and spleen.

The negative impact of E. cecorum on broiler economics, health, and welfare

Enterococcus cecorum can harm broiler health, welfare, and economics. This can result in decreased profitability for broiler producers.

The broiler flocks infected with E. cecorum may have reduced feed intake/ nutrient absorption and reduced growth rates, leading to a higher feed conversion ratio, longer production cycles, and lower weight gain. The morbidity and mortality from E. cecorum infection can be as high as 35 % and 15%, respectively. The higher condemnations of up to 9.75% at the processing plant can further add to the losses (Jung et al., 2018).  This can result in significant economic losses for producers.

Further, E. cecorum infections can impair the immune function of broilers, making them more susceptible to other pathogens and reducing their overall health and welfare. Pathogenic E. cecorum is an opportunistic pathogen that can gain momentum during coinfection with E. coli and other gut pathogens, causing a leaky gut. Therefore, a holistic approach to gut health management may help reduce the losses.

E Cecorum

Antibiotic resistance in E. cecorum

E. cecorum has been found to be resistant to multiple antibiotics. Multidrug resistant pathogenic E. cecorum could be recovered from lesions in whole birds for sale at local grocery stores (Suyemoto et al., 2017). Antibiotic resistance can make it difficult to treat and control infections in broilers. This can lead to increased use of multiple antibiotics, which can contribute to the development of antibiotic-resistant bacteria and pose a risk to human health.

Transmission of E. cecorum in broiler flocks

Despite the rapid global emergence of this pathogen, and several works on the subject, the mechanism by which pathogenic E. cecorum spreads within and among vertically integrated broiler production systems remains unclear (Jung et. al.2018). The role of vertical transmission of pathogenic E. cecorum remains elusive. Experimentally infected broiler breeders apparently do not pass the bacterium into their eggs or embryos (Thoefner and Peter, 2016). However, it has been noted that a very low frequency of infected chicks can cause a flock-wide outbreak.

Horizontal transmission: E. cecorum can be transmitted between birds within a flock through direct contact or exposure to contaminated feces, feed, or water.

While the mode of transmission between flocks has not been definitively identified, pathogenic E. cecorum demonstrates rapid horizontal transmission within flocks. It can spread rapidly within flocks via fecal-oral transmission.

Personnel and equipment: E. cecorum can be introduced into a flock through personnel or equipment that has been in contact with infected birds or contaminated materials. For example, personnel working with infected flocks or equipment used in infected flocks can spread the pathogen to uninfected flocks.

Symptoms and diagnosis of E. cecorum in broilers

Enterococcus cecorum infections in broilers can present a range of symptoms, from mild to severe. The most common symptom noticed with E. cecorum is paralysis, which is due to an inflammatory mass that develops in the spinal column at the level of the free thoracic vertebra (FTV). Recognition of this spinal lesion has given rise to several disease names for pathogenic E. cecorum infection, which include vertebral osteomyelitis, vertebral enterococcal osteomyelitis and arthritis, enterococcal spondylitis (ES), spondylolisthesis and, colloquially, “kinky-back” (Jung et al. 2018).

E. cecorum infections can exhibit increased mortality due to septicemia in the early growing period. In this sepsis phase, the clinical signs of E. cecorum may include fibrinous pericarditis, perihepatitis, and air-sacculitis. These lesions might be confused with other systemic bacterial infections like colibacillosis. Therefore, a pure culture is needed for the correct diagnosis of E. cecorum.

The second phase of mortality due to dehydration and starvation of the paralyzed birds can be observed during the finisher phase peaking during 5-6 weeks of age. Paralysis from infection of the free thoracic vertebra is the most striking feature of this disease, with affected birds exhibiting a classic sitting position with both legs extended cranially (Brost et al., 2017).

Diagnosis of E. cecorum in broilers can be challenging, as the symptoms of infection can be similar to those of other bacterial or viral infections. However, a combination of clinical signs, post-mortem examination, and laboratory testing can help to confirm the presence of E. cecorum. Laboratory tests such as bacterial culture and polymerase chain reaction (PCR) can be used to identify the pathogen and also to determine its antibiotic susceptibility. Veterinarians and poultry health professionals can work with producers to develop a diagnostic plan and implement appropriate control measures to manage E. cecorum infections in broiler flocks.

E Cecorum

Prevention and Control of Enterococcus cecorum

The broiler producers/ managers should work with their veterinarians and poultry health professionals to develop an integrated approach to control the spread of E. cecorum and prevent its negative impact on broiler health and productivity.

Currently, there is no commercial vaccine available for preventing pathogenic E. cecorum infection. Therefore, controlling Enterococcus cecorum infection in broiler flocks requires a multifaceted approach that addresses the various modes of transmission and bacterial resistance to antibiotics.

Implementing strict biosecurity protocols, such as controlling access to the farm, disinfecting equipment and facilities, and implementing proper hygiene protocols throughout the integrated broiler operation, can help to minimize the risk of transmission.

Thorough washing of trays and chick boxes in the hatchery with hot water (60-62°C) mixed with an effective disinfectant can reduce the possible vertical transmission of E. cecorum. The vertical transmission may also be prevented by adopting the practice of separating the dirty floor eggs from clean hatching eggs and setting them in the lower racks of the incubator.

Generally, pathogenic isolates from poultry were found to be significantly more drug-resistant than commensal strains (Borst et al., 2012). The selection of an effective antibiotic for the treatment of E. cecorum should be made based on the results of the antibiotic sensitivity test. Antibiotic therapy may not help with paralyzed birds, which ultimately need to be culled. Reducing the use of antibiotics and implementing prudent use practices can help to reduce the development of antibiotic resistance in E. cecorum and other bacteria.

Probiotics can help to maintain the balance of the gut microbiota and may have a protective effect against E. cecorum infections. Fernandez et al. (2019) reported the inhibitory activities of proprietary poultry Bacillus strains against pathogenic isolates of E. cecorum in vitro, but effects are highly strain-dependent and vary significantly among different pathogenic isolates.

Phytogenic compounds and organic acids have been shown to have antimicrobial properties. Phytomolecule-based preparations may help to control E. cecorum infections in broiler flocks in the first week of life, reducing the chances of its translocation from the intestine.

Phytomolecules-based liquid formulations for on-farm drinking water application can also be a handy tool to manage gut health challenges, especially during risk periods in the life of broilers. Such liquid phytomolecule preparations can help to quickly achieve the desired concentration of the active ingredients for a faster antimicrobial effect.

However, these alternatives to antibiotics may be effective only when the E. cecorum is still localized within the gut during the first two weeks of the broiler chicken’s life.

Phytomolecules, also known as phytochemicals, are naturally occurring plant compounds that have been found to have antimicrobial properties. Especially for commercial poultry, nutraceuticals such as phytochemicals showed promising effects, improving the intestinal microbial balance, metabolism, and integrity of the gut due to their antioxidant, anti-inflammatory, immune modulating, and bactericidal properties (Estevez, 2015). Phytogenic compounds have been studied for their potential use in controlling gut pathogens in poultry. Here are some of the roles that phytomolecules can play in controlling gut pathogens:

Antimicrobial activity: Several phytomolecules, such as essential oils, flavonoids, and tannins, have been found to have antimicrobial activity.  Hovorková et al (2018) studied the inhibitory effects of hydrolyzed plant oils (palm, red palm, palm kernel, coconut, babassu, murumuru, tucuma, and Cuphea oil) containing medium-chain fatty acids (MCFAs) against Gram-positive pathogenic and beneficial bacteria. They concluded that all the hydrolyzed oils were active against all tested bacteria (Clostridium perfringens, Enterococcus cecorum, Listeria monocytogenes, and Staphylococcus aureus), at 0.14–4.5 mg/ml, the same oils did not show any effect on commensal bacteria (Bifidobacterium spp. and Lactobacillus spp.). However, further research is needed to test the in-vivo efficacy of phytogenic compounds against pathogenic E. cecorum infections in poultry.

Anti-inflammatory activity: The other coinfecting gut pathogens of E. cecorum can cause inflammation in the intestinal tract of poultry. This can lead to reduced feed intake and growth. Some phytomolecules have been found to have anti-inflammatory activity and can reduce the severity of inflammation. Capsaicin, a naturally occurring bioactive compound in chili peppers, was found to have antioxidant and anti-inflammatory activity. The tendency of capsaicin to substantially diminish the release of COX-2 mRNA is thought to be the reason for its anti-inflammatory effects (Liu et al., 2021).  Thyme oil reduced the synthesis and gene expression of TNF-α, IL-1B, and IL-6 in activated macrophages in a dose-dependent manner, with upregulation of IL-10 secretion (Osana and Reglero, 2012). Cinnamaldehyde has been shown to decrease the expression of several cytokines, such as IL-1 β, IL-6, and TNF-α, as well as iNOS and COX-2, in in-vitro studies (Pannee et al., 2014).

Antioxidant activity: Oxidative stress may contribute to the development of E. cecorum infections in poultry. Phytomolecules, such as polyphenols and carotenoids, have been found to have antioxidant activity and can reduce oxidative stress in the gut of poultry, which can help to prevent E. cecorum infections. Polyphenols widely exist in a variety of plants and have been used for various purposes because of their strong antioxidant ability (Crozier et al., 2009). Quercetin, a flavonoid compound widely present in vegetables and fruits, is well-known for its potent antioxidant effects (Saeed et al., 2017).

Phytomolecules can also modulate the immune system of poultry, which can help to prevent E. cecorum infections. For example, some flavonoids and polysaccharides have been found to enhance the immune response of poultry. Fahnani et. al. (2019) found that supplementing broiler chickens with a combination of flavonoids and polysaccharides extracted from the mushroom Agaricus blazei enhanced their immune response.

Overall, phytomolecules have shown promise in supporting the optimum gut health of poultry. Many phytogenic preparations available in the market can be regarded as an important tool to reduce the use of antibiotics in animal production and mitigate the risk of antimicrobial resistance. However, more research is needed to develop an effective combination of active ingredients, as well as strategies for their use in controlling E. cecorum infections in poultry.

Conclusion

In conclusion, the emergence of pathogenic strains of E. cecorum is becoming a major concern for broiler producers globally. This bacterial pathogen can cause significant economic losses in the broiler industry by affecting the overall health and productivity of the birds. Pathogenic E. cecorum infection can lead to clinical signs including diarrhea, decreased feed intake, reduced growth rate, and increased mortality. Proactive measures must be taken to prevent the introduction and spread of pathogenic E. cecorum in broiler flocks. Implementing strict biosecurity protocols and proper disinfection procedures can help reduce the risk of E. cecorum infection. The use of effective antibiotics after receiving the results of the antibiotics sensitivity test is a crucial step in controlling the infection. Phytomolecule-based preparations can be a potential alternative to control the load of E. cecorum by maintaining optimum gut health to minimize economic losses. Moreover, ongoing surveillance and monitoring of pathogenic E. cecorum prevalence in the broiler industry can assist in the timely detection and control of outbreaks.

In summary, the emergence of pathogenic E. Cecorum as a profit killer in the broiler industry warrants careful attention and proactive management practices to minimize its impact.

References:

Borst, L. B., M. M. Suyemoto, A. H. Sarsour, M. C. Harris, M. P. Martin, J. D. Strickland, E. O. Oviedo, and H. J. Barnes. “Pathogenesis of Enterococcal Spondylitis Caused by Enterococcus cecorum in Broiler Chickens”. Vet. Pathol. 54:61-73. 2017.

Crozier A., Jaganath I.B., Clifford M.N. “Dietary phenolics: Chemistry, bioavailability and effects on health”. Nat. Prod. Rep. 2009;26:1001–1043.

De Herdt, P., P. Defoort, J. Van Steelant, H. Swam, L. Tanghe, S. Van Goethem, and M.

593 Vanrobaeys. “Enterococcus cecorum osteomyelitis and arthritis in broiler chickens”. Vlaams Diergeneeskundig Tijdschrift 78:44-48. 2009.

Estévez, M. “Oxidative damage to poultry: From farm to fork”. Poult. Sci. 2015, 94, 1368–1378.

Fanhani, Jamile & Murakami, Alice & Guerra, Ana & Nascimento, Guilherme & Pedroso, Raíssa & Alves, Marília. (2016). “Agaricus blazei in the diet of broiler chickens on immunity, serum parameters and antioxidant activity”. Semina: Ciencias Agrarias. 37. 2235-2246.

Hovorková P., Laloučková K., Skřivanová E. (2018): “Determination of in vitro antibacterial activity of plant oils containing medium-chain fatty acids against Gram-positive pathogenic and gut commensal bacteria”. Czech J. Anim. Sci., 63: 119-125.

Jung, A., and S. Rautenschlein. “Comprehensive report of an Enterococcus cecorum infection in a broiler flock in Northern Germany. BMC Vet. Res. 10:311. 2014.

Jung, A., M. Metzner, and M. Ryll. “Comparison of pathogenic and non-pathogenic Enterococcus cecorum strains from different animal species”. BMC Microbiol. 17:33. 2017.

Jung, Arne, Laura R. Chen, M. Mitsu Suyemoto, H. John Barnes, and Luke B. Borst. “A Review of Enterococcus Cecorum Infection in Poultry.” Avian Diseases 62, no. 3 (2018): 261–71.

Liu, S.J.; Wang, J.; He, T.F.; Liu, H.S.; Piao, X.S. “Effects of natural capsicum extract on growth performance, nutrient utilization, antioxidant status, immune function, and meat quality in broilers”. Poult. Sci. 2021, 100, 101301.

Martin, L. T., M. P. Martin, and H. J. Barnes. “Experimental reproduction of enterococcal spondylitis in male broiler breeder chickens”. Avian Dis. 55:273-278. 2011.

Ocaña, A.; Reglero, G. “Effects of thyme extract oils (from Thymus Vulgaris, Thymus Zygis and Thymus hyemalis) on cytokine production and gene expression of OxLDL-stimulated THP-1-macrophages”. J. Obes. 2012, 2012, 104706.

Pannee C, Chandhanee I, Wacharee L. “Antiinflammatory effects of essential oil from the leaves of Cinnamomum cassia and cinnamaldehyde on lipopolysaccharide-stimulated J774A.1 cells”. J Adv Pharm Technol Res. 2014 Oct;5(4):164-70. 

Saeed, M.; Naveed, M.; Arain, M.A.; Arif, M.; Abd El-Hack, M.E.; Alagawany, M.; Siyal, F.A.; Soomro, R.N.; Sun, C. “Quercetin: Nutritional and beneficial effects in poultry”. World’s Poult. Sci. J. 2017, 73, 355–364.

Suyemoto, M. M., H. J. Barnes, and L. B. Borst. “Culture methods impact recovery of antibiotic-resistant Enterococci including Enterococcus cecorum from pre- and postharvest chicken”. Lett. Appl. Microbiol. 64:210-216. 2017.

Thoefner, I. C., Jens Peter. Investigation of the pathogenesis of Enterococcus cecorum after 736 intravenous, intratracheal or oral experimental infections of broilers and broiler breeders. In: 737 VETPATH. Prato, Italy. 2016.

 




Mycotoxins affect intestinal health and productivity in broiler breeders

By Han Zhanqiang, Poultry Technical Manager, EWN China

Poultry meat accounts for more than one-third of global meat production. With increasing demand levels, the industry faces several challenges. Among them is the continuous supply of day-old chicks, which is affected by various issues. Mitigation strategies should be taken to ensure the supply of good quality day-old chicks to production farms.

Fast-growing broilers versus fit breeders

The poultry industry is challenged by the broiler-breeder paradox: on the one hand, fast-growing broilers are desirable for meat production. On the other hand, the parents of these broilers have the same genetic traits, but in order to be fit for reproduction, their body weight should be controlled. Thus, feed restriction programs, considering breeder nutritional requirements, are necessary to achieve breed standards for weight, uniformity, body structure, and reproductive system development, determining the success of day-old chick production.

Mycotoxins affect breeder productivity

During the rearing period, gut health problems such as coccidiosis, necrotic enteritis, and dysbiosis affect flocks. Also during the laying period, breeder flocks are also susceptible to disturbances in gut health, especially during stressful periods, leading to reduced egg production and an increase in off-spec eggs. One measure to restrain these challenges is the strict quality control of the feed. In this context, contamination with mycotoxins is an important topic. However, due to the nature of fungal contamination and limitations of sampling procedures, mycotoxins may not be detected or may be present at levels considered low and not risky.

Existing studies on mycotoxins in breeders indicate that mycotoxins can cause varying degrees of reduction in egg production and hatchability and are also associated with increased embryonic mortality. Recent studies have shown that low levels of mycotoxins interact with other stressors and may lead to reduced productivity. These losses are often mistaken for normal breeder lot variation. However, they cause economic losses far greater than normal flock-to-flock variability.

Mycotoxins impair the functionality of the gut

Low mycotoxin levels affect gut health. Individually and in combinations, mycotoxins such as DON, FUM, and T2 can impact gut functions such as digestion, absorption, permeability, immunity, and microbial balance. This is critical in feed-restricted flocks because it decreases body weight and uniformity, and in laying animals, egg production and egg quality can be reduced. Absorption of calcium and vitamin D3, which are critical for eggshell formation, depends on gut integrity and the efficiency of digestion and absorption. These factors can be adversely affected by even low mycotoxin levels: eggshells can become thin and brittle, thereby reducing hatching eggs and increasing early embryo mortality.

Prevention is the key to success in day-old chick production, therefore:

  • avoid the use of raw materials with known mycotoxin contamination.
  • use feed additives prophylactically, especially with anti-mycotoxin and antioxidant properties.

Prevention is an alternative approach to assure health and productivity in -many times unknown- mycotoxin challenges.

Figure Effect Of MycotoxinsFigure 1: Effect of mycotoxins on eggshell quality and embryo death (Caballero, 2020)

University trial shows anti-mycotoxin product improving performance

A recent study by the University of Zagreb confirmed that long-term (13 weeks) exposure to feed contaminated with mycotoxins has an impact on egg production performance – a challenge that could be counteracted by using an anti-mycotoxin product.

The negative control (NC) was offered feed without mycotoxins. In contrast, the challenged control (CC), as well as a third group, received feed contaminated with 200ppb of T2, 100ppb of DON, and 2500ppb of FMB1. To the feed of the third group, an anti-mycotoxin feed additive (Mastersorb Gold, EW Nutrition) was given on top (CC+MG).

Figure Influence On Feed IntakeFigure 2: Influence of mycotoxins on feed intake and the effect of the anti-mycotoxin product Mastersorb Gold

Figure Cumulative Number Of EggsFigure 3: The effect of mycotoxins on the cumulative number of eggs and the compensating effect of Mastersorb Gold

Figure Cumulative Egg MassFigure 4: The impact of mycotoxins on the cumulative egg mass and the countereffect of Mastersorb Gold

As expected, the contaminated feed reduced feed intake, egg production, and egg weight (Fig. 2-4). Moreover, the liver and gut were affected which was evidenced in histopathological lesion scores of the organs: the control group had the lowest score, followed by the group fed Mastersorb Gold. The challenged group without any anti-mycotoxin product scored the highest.

Breeders are susceptible to mycotoxins and need our support

Broiler breeders and day-old chick production can be affected by long-term exposure to mycotoxins, which often exceeds the tolerance range of average flocks. To reduce or even prevent the potential impact of mycotoxins, a comprehensive management strategy is crucial. This includes responsible raw material procurement, storage, and feed processing leading to high feed quality, and the consideration of breeders’ nutrient demands. The inclusion of highly effective products to manage mycotoxin risk is an additional tool to maintain breeder performance.




Managing gut health – a key challenge in ABF broiler production

By Dr. Ajay Bhoyar, Global Technical Manager Poultry, EW Nutrition

Gut health is a critical challenge in antibiotics-free (ABF) production as it plays a vital role in the overall health and well-being of animals. Antibiotics have long been used as a means of preventing and treating diseases in animals, but their overuse has led to the development of antibiotic-resistant bacteria. As a result, many farmers and producers are shifting towards antibiotics-free production methods. This shift presents a significant challenge as maintaining gut health without antibiotics can be difficult. It is, however, not impossible.

One of the main challenges in antibiotics-free production is the prevention of bacterial infections in the gut. The gut microbiome plays a crucial role in the immune system and overall health of animals. When the balance of microbes in the gut is disrupted (dysbiosis), it can lead to poor nutrient absorption which subsequently results in reduced live bird performance including feed efficiency and weight gain in broiler chicken. In the absence of antibiotics, farmers and producers must rely on other methods to maintain a healthy gut microbiome.

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Antibiotic reduction – a major global trend

The trend in recent years has been for poultry producers to reduce their use of antibiotics to promote public health and improve the sustainability of their operations. This has been driven by concerns about the development of antibiotic-resistant bacteria and the potential impact on human health, as well as by consumer demand for meat produced without antibiotics. Many countries now have regulations in place that limit the use of antibiotics in food and animal production.

Challenges to antibiotics-free poultry (ABF) production

  1. Disease control. Antibiotic-free poultry production requires farmers to rely on alternative methods for controlling and preventing diseases, such as stepped-up biosecurity practices. This can be more labor-intensive and costly.
  2. Higher mortality rates. Without antibiotics, poultry farmers may experience higher mortality rates due to disease outbreaks and other health issues. This can lead to financial losses for the farmer and a reduced supply of poultry products for consumers.
  3. Feeding challenges. Antibiotic growth promotors (AGPs) are often used in feed to promote growth and prevent intestinal disease in poultry. Without AGPs, poultry producers can find alternative ways to ensure expected production performance.
  4. Increased cost. Antibiotic-free poultry production can be more expensive than conventional production methods, as farmers must invest in additional housing, equipment, labor, etc.

Phasing out AGPs will likely lead to changes in the microbial profile of the intestinal tract. It is hoped that strategies such as infectious disease prevention programs and using non-antibiotic alternatives minimize possible negative consequences of antibiotic removal on poultry flocks (Yegani and Korver, 2008).

Gut health is key to overall health

A healthy gastrointestinal system is important for poultry to achieve its maximum production potential. Gut health in poultry refers to the overall well-being and functioning of the gastrointestinal tract in birds. This includes the balance of beneficial bacteria, the integrity of the gut lining, and the ability to digest and absorb nutrients. Gut health is important for maintaining the overall health and well-being of the birds. A healthy gut helps to improve feed efficiency, nutrient absorption, and the overall immunity of the birds.

The gut is host to more than 640 different species of bacteria and 20+ different hormones. It digests and absorbs the vast majority of nutrients and makes up for nearly a quarter of body energy expenditure. It is also the largest immune organ in the body (Kraehenbuhl and Neutra, 1992). Consequently, ‘gut health’ is highly complex and encompasses the macro and micro-structural integrity of the gut, the balance of the microflora, and the status of the immune system (Chot, 2009).

Poultry immunity is mediated by the gut

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, which are clusters of immune cells located in the gut wall, as well as the gut-associated lymphocytes (GALs) that are found throughout the gut. These immune cells are responsible for recognizing and responding to pathogens that enter the gut.

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

The gut microbiome also plays a critical role in gut-mediated immunity in chickens. The gut microbiome is made up of a highly varied community of microorganisms, and these microorganisms can have a significant impact on the immune response. For example, certain beneficial bacteria can help to stimulate the immune response and protect the gut from pathogens.

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

Dysbiosis/Dysbacteriosis impacts performance

Dysbiosis is an imbalance in the gut microbiota because of an intestinal disruption. Dysbacteriosis can lead to wet litter and caking issues. Prolonged contact with the caked litter can lead to pododermatitis (feet ulceration) and hock-burn, resulting in welfare issues as well as degradation of the carcass (Bailey, 2010). Apart from these issues, the major economic impact comes from reduced growth rates, FCR, and increased veterinary treatment costs. Coccidiosis infection and other enteric diseases can be aggravated when dysbiosis is prevalent. Generally, animals with dysbiosis have high concentrations of Clostridium that generate more toxins, leading to necrotic enteritis.

FigureFig.1: Dysbiosis – a result of challenging animal’s microbiome. Source: Charisse Petersen and June L. Round. 2014

It is believed that both non-infectious and infectious factors can play a role in dysbacteriosis (DeGussem, 2007). Any changes in feed and feed raw materials, as well as the physical quality of feed, influence the balance of the gut microbiota. There are some risk periods during poultry production when the bird will be challenged, for example during feed change, vaccination, handling, transportation, etc. During these periods, the gut microbiota can fluctuate and, in some cases, if management is sub-optimal, dysbacteriosis can occur.

Infectious agents that potentially play a role in dysbacteriosis include mycotoxins, Eimeria spp., Clostridium perfringens, and other bacteria producing toxic metabolites.

Factors affecting gut health

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

  1. Feed and water quality: The form, type, and quality of feed provided to broilers can significantly impact their gut health. Consistent availability of cool and hygienic drinking water is crucial for optimum production performance.
  2. Stress: 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.
  3. Microbial exposure: Exposure to pathogens or other harmful bacteria can disrupt the gut microbiome and lead to gut health issues.
  4. Immune system: 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. Sanitation: Keeping the broiler environment clean and free of pathogens is crucial for maintaining gut health, as bacteria and other pathogens can easily spread and disrupt the gut microbiome.
  6. Management practices: Proper management practices, such as proper feeding and watering, and litter management can help to maintain gut health and prevent gut-related issues.

Chat GutFig. 2. Key factors affecting broilers’ gut health

Key approaches for managing gut health without antibiotics

Two key approaches for managing gut health in poultry without the use of antibiotics are outstandingly successful.

Proper nutrition and management practices

Ensuring the birds have access to clean water, high-quality feed, and a stress-free environment is crucial for ABF poultry production. A balanced diet in terms of protein, energy, and essential vitamins and minerals is essential for maintaining gut health.

The environment in which birds have kept plays a major role in maintaining gut health. Proper sanitation and ventilation, as well as the right temperature and humidity, are crucial to prevent the spread of disease and infection. There is no alternative to the strict implementation of stringent biosecurity measures to prevent the spread of disease.

Early detection and treatment of diseases can help to prevent them from becoming more serious problems affecting the profitability of ABF production. It is important to keep a close eye on birds for signs of disease, such as diarrhea, reduced water, and feed consumption.

Gut health-promoting feed additives

Another approach to maintaining gut health in antibiotics-free poultry production is using gut health-supporting feed additives. A variety of gut health-supporting feed additives including phytochemicals/essential oils, organic acids, probiotics, prebiotics, exogenous enzymes, etc. in combination or alone are used in animal production. Particularly, phytogenic feed additives (PFAs) have gained interest as cost-effective feed additives with already well-established effects on improving broiler chickens’ intestinal health.

Plant secondary metabolites and essential oils (generically called phytogenics, phytochemicals, or phytomolecules) are biologically active compounds that have recently garnered interest as feed additives in poultry production, due to their capacity to improve feed efficiency by enhancing the production of digestive secretions and nutrient absorption. This helps reduce the pathogenic load in the gut, exert antioxidant properties and decrease the microbial burden on the animal’s immune status (Abdelli et al. 2021).

Plant extracts – Essential oils (EOs) /Phytomolecules

Phytochemicals are naturally occurring compounds found in plants. Many phytomolecules have been found to have antimicrobial properties, meaning they can inhibit the growth or kill microorganisms such as bacteria, viruses, and fungi. Examples of phytomolecules with antimicrobial properties include compounds found in garlic, thyme, and tea tree oil. Essential oils (EOs) are raw plant extracts (flowers, leaves, roots, fruit, etc.) whereas phytomolecules are active ingredients of essential oils or other plant materials. A phytomolecule is clearly defined as one active compound. 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).

A wide variety of herbs and spices (thyme, oregano, cinnamon, rosemary, marjoram, yarrow, garlic, ginger, green tea, black cumin, and coriander, among others), as well as EOs (from thyme, oregano, cinnamon, garlic, anise, rosemary, citruses, clove, ginger), have been used in poultry, individually or mixed, for their potential application as AGP alternatives (Gadde et al., 2017).

Table DataFig. 3: Phytomolecule-based feed additive outperforms AGPs with improved broiler performance (42 Days field study)

One of the primary modes of action of EOs is related to their antimicrobial effects which allow for controlling potential pathogens (Mohammadi and Kim, 2018).

Phytomolecule blend  Clostridium perfringens Enterococcus caecorum Enterococcus hirae Escherichia coli Salmonella typhimurium  Staphylococcus aureus
Ventar D 1250 2500 5000 2500 5000 2500

Fig. 4: Effectivity of phytomolecule-based feed additive (Ventar D) against enteropathogenic bacteria (MIC value in PPM)

Phytomolecules have been shown to have anti-inflammatory properties. These compounds include flavonoids, polyphenols, carotenoids, and terpenes, among others. One of the ways in which phytomolecules exhibit anti-inflammatory effects is through their ability to inhibit the activity of pro-inflammatory enzymes and molecules. For example, polyphenols have been shown to inhibit the activity of nuclear factor-kappa B (NF-kB), a transcription factor that plays a key role in regulating inflammation.

Phytomolecules also have antioxidant properties, which can help to protect cells from damage caused by reactive oxygen species (ROS) and other reactive molecules that can contribute to inflammation. Plant extracts are also proposed to be used as antioxidants in animal feed, protecting animals from oxidative damage caused by free radicals. The presence of phenolic OH groups in thymol, carvacrol, and other plant extracts act as hydrogen donors to the peroxy radicals produced during the first step in lipid oxidation, thus retarding the hydroxyl peroxide formation (Farag et al., 1989, Djeridane et al., 2006). Thymol and carvacrol are reported to inhibit lipid peroxidation (Hashemipour et.al. 2013) and have strong antioxidant activity (Yanishlieva et al., 1999).

Overall, the anti-inflammatory effects of phytomolecules are thought to be due to a combination of their ability to inhibit the activity of pro-inflammatory enzymes and molecules, their antioxidant properties, and their ability to modulate the immune system. Plant extracts (i.e. carvacrol, cinnamaldehyde, eugenol. etc.) inhibit the production 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). It has been indicated that anti-inflammatory activities may be partially mediated by blocking the NF-κB activation pathway (Lee et al., 2005).

Table DataFig. 5: Anti-inflammatory effect of phytomolecule-based feed additive (Ventar D) – the reduced activity of inflammatory cytokines

Proper protection of EOs/Phytomolecules is key to optimum results

Several phytogenic compounds have also been shown to be largely absorbed in the upper GIT, meaning that without proper protection, the majority would not reach the lower gut where they would exert their major functions (Abdelli et al. 2021). The benefits of supplementing the broiler diet with a mixture of encapsulated EOs were higher than the tested PFA in powdered, non-protected form (Hafeez et al. 2016). Novel delivery technologies have been developed to protect PFAs from the degradation and oxidation process during feed processing and storage, ease the handling, allow a slower release, and target the lower GIT (Starčević et al. 2014). The specific protection techniques used during the commercial production of an EO/phytomolecule blend are crucial in delivering on all the objectives with remarkable consistency.

Table Data

Fig. 6: Pelleting stability of phytomolecule – based feed additive (Ventar D) at high temperature and longer conditioning time

Phytomolecule blend optimizes production performance

Removal of antibiotics in poultry production can be challenging for controlling mortality and maintaining the production performance of the birds. Phytogenic feed additives have been shown to improve production performance of chicken due to their antimicrobial, anti-inflammatory, antioxidant, and digestive properties. Possible mechanisms behind improved nutrient digestibility by phytogenic feed additives (PFAs) supplementation could be attributed to the ability of these feed additives to stimulate appetite, saliva secretion, intestinal mucus production, bile acid secretion, and activity of digestive enzymes such as trypsin and amylase as well as to positively affect the intestinal morphology (Oso et al. 2019). EOs are perceived as growth promoters in poultry diets, with strong antimicrobial and anticoccidial activities (Zahi et al., 2018). PFAs have positive effects on body weight gain and FCR in chickens (Khattak et al. 2014, Zhang et el. 2009).

Table Data
Fig. 7: Phytomolecule-based feed additive improved broiler FCR and mortality in field trial

Conclusion

In conclusion, managing gut health is a significant challenge in ABF broiler production that must be addressed to achieve optimal performance and welfare of the birds. The use of antibiotics as a preventative measure in broiler production has been widely used, but with the increasing demand for antibiotic-free products, alternative methods to maintain gut health must be implemented. These include using gut health-supporting feed additives, and proper management practices such as implementing biosecurity measures, maintaining optimal environmental conditions, providing adequate space and ventilation, and reducing stress. However, it is essential to note that there is no one-size-fits-all solution for gut health management in ABF broiler production. It is important to continuously monitor and assess their flock’s gut health and make adjustments as necessary. Additionally, research and development in this field should be encouraged to identify new and innovative ways to maintain gut health in ABF broiler production.

Overall, managing gut health is a critical challenge that requires a multi-faceted approach and ongoing monitoring and management. By implementing the appropriate strategies and utilizing new technologies, poultry operators can ensure the health and well-being of their flocks while meeting the growing demand for antibiotic-free products sustainably.

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Djeridane A., M. Yousfi M, Nadjemi B, Boutassouna D., Stocker P., Vidal N. Antioxidant activity of some Algerian medicinal plants extracts containing phenolic compounds. Food Chem, 97 (2006), pp. 654-660

Farag R. S., Daw Z.Y., Hewedi F.M., El-Baroty G.S.A. Antimicrobial activity of some Egyptian spice essential oils. J Food Prot, 52 (1989), pp. 665-667

Gadde U., Kim W.H., Oh S.T., Lillehoj H.S. Alternatives to antibiotics for maximizing growth performance and feed efficiency in poultry: A review. Anim. Health Res. Rev. 2017;18:26–45.

Guo, F.C., Kwakkel, R.P., Williams, B.A., Li, W.K., Li, H.S., Luo, J.Y., Li, X.P., Wei, Y.X., Yan, Z.T. and Verstegen, M.W.A., 2004. Effects of mushroom and herb polysaccharides, as alternatives for an antibiotic, on growth performance of broilers. British Poultry Science45(5), pp.684-694.

Hafeez A., Männer K., Schieder C., Zentek J. Effect of supplementation of phytogenic feed additives (powdered vs. encapsulated) on performance and nutrient digestibility in broiler chickens. Poult. Sci. 2016;95:622–629.

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How to develop phytogenic feed additives

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By Technical Team, EW Nutrition

Modern feed additives are now commonly used as a critical tool to improve animal health. Among these, phytogenic feed additives are increasingly widely adopted. Consequently, more and more products are entering the market, leaving producers to wonder how these products differ from one another and which product performs best. To better understand the benefits that phytogenic feed additives can bring to operations, one must understand the development process feed additives undergo.

develop phytogenic feed additives for chicken

Not all feed additives are born equal

Feed additives are products that are added into an animal feed to improve its value. They are typically used to improve animal performance and welfare and consequently to optimize profitability for livestock producers.

Their purpose should not be confused with that of veterinary drugs. Feed additives provide additional benefits beyond the physiological needs of the animals and should be combined with other measures to improve production efficiency. Those measures include improvements in management, selection of genetics, and a constant review of biosecurity measures.

Several categories of feed additives exist. They all have in common that they are mixed into the feed or premix or the drinking water in relatively low inclusion rates to serve a specific purpose. Examples of feed additives are organic acids, pre- and probiotics, short and medium chained fatty acids, functional yeast products, and phytogenic feed additives. Modern feed additives also blend those different additives into combination products, increasing the value of the final products.

Phytogenic feed additives are a sub-category of additives containing phytomolecules, active ingredients which originate from plants and provide a unique set of characteristics. These molecules are produced by plants to protect themselves from molds, yeasts, bacteria, and other harmful organisms. Depending on the type of molecule, phytomolecules have different properties, ranging from antimicrobial to antioxidant and anti-inflammatory.

EW Nutrition’s approach to developing Ventar D: 6 steps

The development of best-in-class phytogenic feed additives is a complex process. For Ventar D, EW Nutrition divided the process into the following steps, which can serve as a template for a successful development process:

  1. Reviewing customer needs
  2. Active ingredient selection
  3. Technical formulation
  4. Application development and scale-up
  5. Performance tests
  6. Safety and regulatory validation

Understanding customer needs

The most important point in developing a feed additive is customer-centricity. Understanding the challenges and needs of producers is crucial to developing feed additive solutions.

In a first step, additive producers need to evaluate and quantify customer needs wherever possible. This is achieved through communication and literature review: Producers, key opinion leaders, and research partners are interviewed, and their challenges are listed. In the next step, those challenges are further analyzed using scientific literature. In a final step, the customer needs are ranked according to their impact on the customer’s profitability.

customer needs

Subsequently, the minimum requirements for the new feed additive are derived. For phytogenic feed additives, this might be, for instance, something like “Improving animal performance and reducing antibiotic use while increasing profitability”. The selected key performance parameters might be, for example, feed efficiency improvements in broilers.

Marketing Research

Meeting unmet needs

Once the customer needs have been understood, the next phase of the development starts. Based on the intended mode of action, certain phytomolecules are chosen based on their described properties. In our example, this might be an antimicrobial mode of action that targets enteropathogenic bacteria in broilers, supporting gut health.

Meeting unmet needs

In this in-vitro process, the selected individual compounds will be tested for their respective antimicrobial efficacy using MIC and MBC testing. Those tests are run using high-purity compounds.

features test

The tests will be conducted using various relevant field strains like E. Coli, S. enterica or C. perfringens. In the next step, the testing will be repeated with commercially available ingredients. The most promising compounds will be tested in more complex mixtures.

Modern phytogenic feed additives are based on the concept of combining different phytomolecules to attack bacteria in diverse ways, with their antimicrobial effects being multi-modal. This mode of action is crucial because it makes it very unlikely that bacteria can develop resistance to combinations of phytomolecules, as they do to antibiotics.

Selecting the right form of application

Feed processing is often a challenge for additives. Many phytomolecules are highly volatile and prone to volatilization and high temperatures. Especially non-protected phytogenic products are negatively affected by high pelleting temperatures and long retention times of the feed in the conditioner. The results are losses in activity.

features test

Therefore, the development of appropriate delivery systems is a preemptive method to ensure the release of the effective compounds where they should be released – in the gut of the animals. Those delivery systems can utilize emulsifiers when applying the additive via the water for drinking, or encapsulation technologies when the new additive is administered via feed.

Due to the importance of mixability, flowability, and pelleting stability for the performance of the feed additives, the exact types of emulsifiers, carrier, and technologies used in their production is often considered corporate intellectual property.

The importance of in-vivo evaluations

In one of the last steps of the development, the newly developed feed additive prototype needs to prove its safety and efficacy in the animal. Hence the need to run evaluation studies to confirm the mode of action chosen in the initial lab phase. Typically, the additive will be tested in the target species in in-house and external research institutes.

farm test

For a phytogenic feed additive, that might entail comparing its effect on body weight gain, feed efficacy, and gut health against different control groups. Additionally, the newly developed feed additive might be compared to existing additives to get a better understanding of its capabilities.

safety test

Dose-finding studies are conducted to verify the chosen dose recommendation and additional overdosing studies are conducted to prove the safety of the additive for both animals and consumers. In certain markets or regulatory environments, additional studies might be required. Those can contain environmental safety assessments or proof that the new additive does not create residues in animal products.

Case study: Ventar D

For Ventar D, the process followed these steps meticulously, in agile iterative development loops that went from the customer need to formulation, testing, scale-up, in-house and external trials, and finally production.

These steps ensured that the final product that reaches the customer’s doorstep delivers on the expectations – and more.

Case study: Ventar D  

Choose your phytogenic products wisely

The plethora of (phytogenic) feed additives in the market leaves producers with many options to choose from. However, only scientifically developed feed additives can be relied upon to optimize both animal health and production profitability. It is important to select reliable feed additive producers who developed their phytogenic product with the customers’ challenges in mind and went through all the steps necessary to create a high-performing and safe additive.