By Ilinca Anghelescu, Global Director Marketing Communications, EW Nutrition

Medications like GLP-1 receptor agonists, such as semaglutide (marketed as Ozempic, Wegovy, Zepbound etc.), have demonstrated startling efficacy in reducing body weight and are now at the forefront of obesity treatment. Since they work primarily by suppressing appetite, an obvious question is being considered across the entire food chain: will weight loss drugs significantly impact the future of agriculture?

More and more voices are answering “yes”. Not only are models showing a significant impact of these drugs over the medium- and long term, but the demand reduction triggered by weight loss drugs will hurt regions where population peak and shifting demand are already lowering the growth potential of certain segments of agriculture.

Changes are already seen in food consumption

Weight loss drugs like semaglutide work by mimicking the GLP-1 hormone, which regulates appetite and insulin secretion. By doing so, these medications reduce hunger and caloric intake, leading to weight loss. They also appear to reduce consumption of alcohol, tobacco, and junk food. While they have been around for more than a decade, they only recently started to be prescribed for the express purpose of weight loss. In the meantime, medical research is yielding increasingly better results at more affordable prices and with easier application, which will lead to much more widespread adoption around the world.

Currently, around 1.7% of the US population is officially prescribed such drugs, although it is hard to know how many people are actually taking this type of medication. Morgan Stanley expects the figure to grow to 7% within ten years – equivalent to well over 23 million people in the US alone. Even with this currently small percentage, retailers are claiming to see effects. Pepsi, Nestle and Walmart are among those preparing to pivot in the face of expected losses.

As more individuals adopt these drugs for weight management, dietary patterns are expected to shift even more, impacting food demand at both individual and population levels. With a 25% reduction in caloric intake for a considerable slice of the world’s over 1 billion obese people, not to mention overweight populations that might take these drugs off-label, the math speaks for itself.

Potential implications for agriculture

1. Crop Production Adjustments: Farmers might adjust crop production to align with changing consumer preferences. Increased demand for fruits, vegetables, and whole grains could lead to a shift in crop priorities, influencing agricultural planning and resource allocation.
2. Livestock Industry: A potential decrease in demand for high-fat meats and increase in demand for leaner meats could impact the livestock industry, leading to changes in breeding, feeding, and marketing strategies. Animal protein, however, remains much less impacted than industries supplying manufacturers of junk food, alcohol, and tobacco.

Changes in consumer demand will inevitably impact food prices and market dynamics, from the field to retail shelves. Increased demand for healthier food options might lead to industry shifts and higher prices initially, but as production scales up, prices could stabilize. This economic transition will require strategic adjustments across the supply chain.

Bonus problem: World population will peak and decline within two generations

To add insult to injury: United Nations demographic models suggest population growth will peak around 10.3 billion in the mid-2080s, then decline. Naturally, the distribution is unequal across the board, with some countries peaking this year and others growing at staggering speeds.

For instance, 63 countries and areas will already see population peaks in 2024 and are expected to decline by 14% over the next 30 years – including China, Russia, Germany, and Japan.

These new demographic models should already shape the long-term plans not just for companies, but for countries and alliances as well – and agriculture will represent a major point of impact. In its case, this map is consistent with FAO’s analysis of growth areas and lends even more credence to the idea of major shifts already felt within a generation. Growth in protein demand will move to what are now seen as developing nations, while developed countries should expect shrinking demand. It is, however, in these developed countries where obesity drugs will hit first and most strongly, lowering demand that is already nearing its peak.

Still: It’s not all bad news!

The emergence of weight loss drugs like semaglutide has the potential to influence dietary patterns significantly, thereby impacting agricultural demand and production. While this is undeniably a challenge, there is a major opportunity here as well: The industries that will be most severely hit do not include healthy protein production. A reduced food intake will likely require a higher quality of nutrition in general, with reduced demand for “empty” calories and increased demand for vitamin-, fiber-, and especially protein-packed meals, tasty as well as nutritionally rich.

Further reading

Wilding, J.P.H., et al. (2021). “Once-Weekly Semaglutide in Adults with Overweight or Obesity.” *New England Journal of Medicine*, 384(11), 989-1002. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

Astrup, A., et al. (2021). “Semaglutide for the treatment of overweight and obesity: A review.” *Diabetes, Obesity and Metabolism*, 23(S1), 39-49. https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.14863

Garnett, T. (2011). “Where are the best opportunities for reducing greenhouse gas emissions in the food system (including the food chain)?” *Food Policy*, 36, S23-S32. https://www.sciencedirect.com/science/article/abs/pii/S0306919210001132

Antimicrobial resistance (AMR) poses a significant threat to global health, driven by the overuse and misuse of antibiotics in both human medicine and livestock farming. In livestock farming, antimicrobials are still used extensively for therapeutic and non-therapeutic purposes. However, estimates of the quantities used per species are notoriously hard to derive from fragmented, incomplete, or unstandardized data around the world.

A recent article (“Global antimicrobial use in livestock farming: an estimate for cattle, chickens, and pigs”, Animal, 18(2), 2024) attempts to update the figures by estimating global biomass at treatment of cattle, pigs, and chickens, considering distinct weight categories for each species in biomass calculation, and using the European Medicines Agency’s weight standards for the animal categories. With these more refined calculations, authors Zahra Ardakani, Maurizio Aragrande, and Massino Canali aim to provide a more accurate estimate of global antimicrobial use (AMU) in cattle, chickens, and pigs. Understanding these patterns is crucial for addressing AMR and developing strategies for sustainable livestock management.

Key Findings

The study estimates that the global annual AMU for cattle, chickens, and pigs amounts to 76,060 tons of antimicrobial active ingredients. This is a significant revision from previous estimates due to a more detailed evaluation of animal weights and categories:

1. Cattle: 40,697 tons (53.5% of total AMU)
2. Pigs: 31,120 tons (40.9% of total AMU)
3. Chickens: 4,243 tons (5.6% of total AMU)

Methodology

The study utilizes the concept of Population Correction Units (PCU) to estimate antimicrobial usage, taking into account the weight and category of livestock at the time of treatment. This method differs from previous approaches that relied on live weight at slaughter, providing a more accurate representation of AMU.

The PCU is calculated by multiplying the number of animals by their average weight during treatment. This approach allows for differentiation by age and sex, which is particularly important for species like cattle and pigs.

Figure 2: (a) Changes in global PCU (million tonnes), (b) changes in global antibiotic use in mg per PCU, and (c) changes in global AMU (thousand tonnes) for cattle, chickens, and pigs; between 2010 and 2020.  Abbreviations: PCU = Population Correction Unit; AMU = Antibiotic Use.

Study shows lower AMU than previous estimates

The study highlights a significant shift in AMU patterns, with chickens showing a remarkable decrease in antimicrobial use despite increased production. This is indicative of improved management and more responsible use of antibiotics in the poultry industry.

The lower AMU in cattle and pigs, compared to previous estimates, underscores the importance of considering animal age and weight at treatment. These findings align closely with World Organization for Animal Health (WOAH) estimates, validating the methodology.

However, the study also acknowledges limitations, including reliance on European standards for average weight at treatment, which may not reflect global variations. Additionally, the lack of comprehensive global data on veterinary antibiotics presents challenges in creating fully accurate estimates.

Corrected estimate highlights improved production advances

This study provides a revised and potentially more accurate estimate of global antimicrobial use in livestock. By accounting for the weight and treatment categories of animals, it offers insights that could guide policy and management practices to mitigate the spread of antimicrobial resistance.

The article also indicates that the industry may have over-estimated antimicrobial usage in livestock and, just as importantly, that antimicrobial use has been kept in check or even reduced, despite increases in farmed animal headcounts. The lower usage is likely due to regulatory oversight and improvements in alternative methods to control and mitigate health challenges.

Part 4: Paleness

By Dr. Inge Heinzl, Editor and Technical Team, EW Nutrition

We already showed bad feathering, mouth and beak lesions, bone issues, and foot pad lesions as signs of mycotoxin contamination in the feed, but there is another indicator: paleness. Paleness can signify a low count of red blood cells resulting from blood loss or inadequate production of these cells. Other possibilities are higher bilirubin levels in the blood due to an impaired liver, leading to jaundice or missing pigmentation.

The mycotoxins mainly causing anemia are Aflatoxins, Ochratoxin, DON, and T-2 toxin

Anemia can be diagnosed using parameters such as red blood cell count, hemoglobin levels, and hematocrit/packed cell volume (PCV). Numerous studies have examined the impact of mycotoxins on hematological parameters. They reveal their propensity to affect red blood cell production by impairing the function of the spleen and inducing hematological alterations. On the other hand, anemia can be caused by blood loss. Due to affecting coagulation factors, mycotoxins can lead to internal hemorrhages. The gut wall damage, probably due to secondary infections such as coccidiosis and necrotic enteritis, can entail bloody diarrhea in various animal species.

Impact on the production of blood cells

Low values of blood parameters such as red blood cells, hemoglobin, and hematocrit can result from inadequate production due to impacted production organs. The World Health Organization (WHO, 1990) and European Commission (European Commission, 2001) have identified hematopoietic tissues as targets for necrosis caused by T-2 toxin. Chu (2003) even stated that “the major lesion of T-2 toxin is its devastating effect on the hematopoietic system in many mammals, including humans”. Pande et al. (2006) suggested that reduced hemoglobin values result from decreased protein synthesis due to mycotoxin contamination, a notion supported by Pronk et al. (2002), who described trichothecenes as potent inhibitors of protein, DNA, and RNA synthesis, particularly affecting tissues with high cell division rates. Additionally, the European Commission (2001) highlighted the sensitivity of red blood cell progenitor cells (in this trial, the cells of mice, rats, and humans) to the toxic effects of T-2 and HT-toxins. DAS also seems to attack the hematopoietic system, as shown in humans (WHO, 1990). A further cause for anemia might be low feed intake or nutrient absorption, which inhibits adequate iron absorption and leads to iron deficiency. In their case report, Bozzo et al. (2023) assumed that renal failure and a resulting impaired excretion capacity caused by OTA might even increase the half-life of the toxins. This would enhance their effects on their target organs, such as the liver and bone marrow, and lead to anemia.

Several studies utilizing different animal species and mycotoxin dosages have been conducted to assess the effects of Aflatoxins, Ochratoxin, and T-2 Toxin on hematological parameters. The following table provides a summary of some of these studies.

Table 1: The effects of different mycotoxins on hematological parameters – hematopoiesis

In their meta-analysis, Andretta et al. (2012) reported that the presence of mycotoxins in broiler diets decreased the hematocrit and the hemoglobin concentration by 5% and 15%, and aflatoxin alone decreased the parameters by 6% and 20%.

It should be evident that a simultaneous occurrence of several mycotoxins even aggravates the situation. In an experiment involving Sprague Dawley rats, administering T-2, DON, NIV, ZEA, NEO, and OTB decreased hematocrit and red blood cell counts across all mycotoxins. However, for DON, NIV, ZEN, and OTB, red blood cell values showed partial recovery after 24 hours (Chattopadhyay, 2013). Perhaps the organism learns to cope with the mycotoxins.

The examples show that Trichothecenes, such as T-2 toxin, DON, and others, as well as Ochratoxins and Aflatoxins, impact blood parameters such as hematocrit, hemoglobin, red blood cell count, and mean corpuscular volume. All these changes might lead to paleness of the skin and birds’ feet and combs.

Blood loss caused by bleeding or destruction of erythrocytes

The second possibility for anemia is blood loss due to injuries or lesions. In addition to directly causing hemorrhages, mycotoxins can promote secondary infections such as coccidiosis, which damages the gut and may produce bloody feces.

Parent-Massin (2004) e.g. reports on rapidly progressing coagulation problems after the ingestion of trichothecenes leading to septicemia and massive hemorrhages. Table 2 shows more examples of mycotoxins causing paleness due to blood loss.

Table 2: The effects of different mycotoxins on hematological parameters – blood loss

Poor pigmentation

The fourth reason for paleness can be inadequate pigmentation. According to Hy Line (2021), the so-called pale bird syndrome is characterized by poor skin and egg yolk pigmentation and is caused by reduced absorption of fat and carotenoid pigments in compromised birds. This is also the case when the diets contain pigment supplements. Tyczkowski and Hamilton (1986) observed in their experiment with chickens exposed to doses of 1-8 µg of Aflatoxins/g of diet for three weeks that aflatoxins can cause poor pigmentation in chickens, probably by impairing carotenoids absorption but also transport and deposition. Osborne et al. (1982) asserted that carotenoids were significantly (P<0.05) depressed by 2 ppm ochratoxin as well as by 2.5 ppm aflatoxin in the diet.

Another possibility is oxidative stress due to the mycotoxin challenge. As pigments also serve as antioxidants, they may be expended for this purpose and are no longer available for pigmentation.

Paleness in poultry – a reason to think about mycotoxins

Paleness can have different causes, some of which are influenced by mycotoxins. If your chickens or hens are pale, checking the feed concerning mycotoxins is always recommended. A feed analysis can give information about possible contamination (see our tool MasterRisk).

In the case of contamination, effective products binding the mycotoxins and mitigating the adverse effects of these harmful substances can help protect your birds. As paleness is usually not the only effect of mycotoxins but also a decrease in growth, toxin binders can help maintain the performance of your animals.

References:

Abdel-Sattar, Ward Masoud, Kadry Mohamed Sadek, Ahmed Ragab Elbestawy, and Disouky Mohamed Mourad. “The Protective Role of Date Palm (Phoenix Dactylifera Seeds) against Aflatoxicosis in Broiler Chickens Regarding Carcass Characterstics, Hepatic and Renal Biochemical Function Tests and Histopathology.” Journal of World’s Poultry Research 9, no. 2 (June 25, 2019): 59–69. https://doi.org/10.36380/scil.2019.wvj9.

Albassam, M. A., S. I. Yong, R. Bhatnagar, A. K. Sharma, and M. G. Prior. “Histopathologic and Electron Microscopic Studies on the Acute Toxicity of Ochratoxin a in Rats.” Veterinary Pathology 24, no. 5 (September 1987): 427–35. https://doi.org/10.1177/030098588702400510.

Andretta, I., M. Kipper, C.R. Lehnen, and P.A. Lovatto. “Meta-Analysis of the Relationship of Mycotoxins with Biochemical and Hematological Parameters in Broilers.” Poultry Science 91, no. 2 (February 2012): 376–82. https://doi.org/10.3382/ps.2011-01813.

Bhat, RameshV, Y Ramakrishna, SashidharR Beedu, and K.L Munshi. “Outbreak of Trichothecene Mycotoxicosis Associated with Consumption of Mould-Damaged Wheat Products in Kashmir Valley, India.” The Lancet 333, no. 8628 (January 1989): 35–37. https://doi.org/10.1016/s0140-6736(89)91684-x.

Bozzo, Giancarlo, Nicola Pugliese, Rossella Samarelli, Antonella Schiavone, Michela Maria Dimuccio, Elena Circella, Elisabetta Bonerba, Edmondo Ceci, and Antonio Camarda. “Ochratoxin A and Aflatoxin B1 Detection in Laying Hens for Omega 3-Enriched Eggs Production.” Agriculture 13, no. 1 (January 5, 2023): 138. https://doi.org/10.3390/agriculture13010138.

Chang, Chao-Fu, and Pat B. Hamilton. “Increased Severity and New Symptoms of Infectious Bursal Disease during Aflatoxicosis in Broiler Chickens.” Poultry Science 61, no. 6 (June 1982): 1061–68. https://doi.org/10.3382/ps.0611061.

Chattopadhyay, Pronobesh, Amit Agnihotri, Danswerang Ghoyary, Aadesh Upadhyay, Sanjeev Karmakar, and Vijay Veer. “Comparative Hematoxicity of Fusarium Mycotoxin in Experimental Sprague-Dawley Rats.” Toxicology International 20, no. 1 (2013): 25. https://doi.org/10.4103/0971-6580.111552.

European Commission. “Opinion of the Scientific Committee on Food on Fusarium Toxins Part 5: T-2 Toxin and HT-2 Toxin.” Food.ec.europa. Accessed May 30, 2001. https://food.ec.europa.eu/document/download/a859c348-a38e-404c-a2af-c3e29a3a8777_en?filename=sci-com_scf_out88_en.pdf.

Giambrone, J.J., U.L. Diener, N.D. Davis, V.S. Panangala, and F.J. Hoerr. “Effect of Purified Aflatoxin on Turkeys.” Poultry Science 64, no. 5 (May 1985): 859–65. https://doi.org/10.3382/ps.0640859.

Gu, Wang, Qiang Bao, Kaiqi Weng, Jinlu Liu, Shuwen Luo, Jianzhou Chen, Zheng Li, et al. “Effects of T-2 Toxin on Growth Performance, Feather Quality, Tibia Development and Blood Parameters in Yangzhou Goslings.” Poultry Science 102, no. 2 (February 2023): 102382. https://doi.org/10.1016/j.psj.2022.102382.

Henry, H., T. Whitaker, I. Rabban, J. Bowers, D. Park, W. Price, F.X. Bosch, et al. “Aflatoxin M1.” Aflatoxin M1 (JECFA 47, 2001). Accessed July 29, 2024. https://inchem.org/documents/jecfa/jecmono/v47je02.htm.

Hoerr, F., W. Carlton, B. Yagen, and A. Joffe. “Mycotoxicosis Caused by Either T-2 Toxin or Diacetoxyscirpenol in the Diet of Broiler Chickens.” Fundamental and Applied Toxicology 2, no. 3 (May 1982): 121–24. https://doi.org/10.1016/s0272-0590(82)80092-4.

Huff, W.E., J.A. Doerr, P.B. Hamilton, and R.F. Vesonder. “Acute Toxicity of Vomitoxin (Deoxynivalenol) in Broiler Chickens,” Poultry Science 60, no. 7 (July 1981): 1412–14. https://doi.org/10.3382/ps.0601412.

Huff, W.E., R.B. Harvey, L.F. Kubena, and G.E. Rottinghaus. “Toxic Synergism between Aflatoxin and T-2 Toxin in Broiler Chickens.” Poultry Science 67, no. 10 (October 1988): 1418–23. https://doi.org/10.3382/ps.0671418.

Hy-Line. “Mycotoxins: How to deal with the threat of mycotoxicosis.” Hy-Line International. Accessed July 29, 2024. https://www.hyline.com/.

Klein, P. J., T. R. Vleet, J. O. Hall, and R. A. Coulombe. “Dietary Butylated Hydroxytoluene Protects against Aflatoxicosis in Turkey.” Poisonous plants and related toxins, November 24, 2003, 478–83. https://doi.org/10.1079/9780851996141.0478.

Kubena, L.F., R.B. Harvey, T.S. Edrington, and G.E. Rottinghaus. “Influence of Ochratoxin A and Diacetoxyscirpenol Singly and in Combination on Broiler Chickens.” Poultry Science 73, no. 3 (March 1994): 408–15. https://doi.org/10.3382/ps.0730408.

Kubena, L.F., R.B. Harvey, W.E. Huff, D.E. Corrier, T.D. Philipps, and G.E. Rottinghaus. “Influence of Ochratoxin A and T-2 Toxin Singly and in Combination on Broiler Chickens.” Poultry Science 68, no. 7 (July 1989): 867–72. https://doi.org/10.3382/ps.0680867.

Kubena, L.F., R.B. Harvey, W.E. Huff, D.E. Corrier, T.D. Phillips, and G.E. Rottinghaus. “Influence of Ochratoxin A and T-2 Toxin Singly and in Combination on Broiler Chickens.” Poultry Science 68, no. 7 (July 1989): 867–72. https://doi.org/10.3382/ps.0680867.

Kubena, L.F., W.E. Huff, R.B. Harvey, T.D. Phillips, and G.E. Rottinghaus. “Individual and Combined Toxicity of Deoxynivalenol and T-2 Toxin in Broiler Chicks.” Poultry Science 68, no. 5 (May 1989): 622–26. https://doi.org/10.3382/ps.0680622.

Lutsky, I.I., and N. Mor. “Alimentary Toxic Aleukia (Septic Angina, Endemic Panmyelotoxicosis, Alimentary Hemorrhagic Aleukia): T-2 Toxin-Induced Intoxication of Cats.” The American journal of pathology, 1980. https://pubmed.ncbi.nlm.nih.gov/6973281/.

Lutsky, Irving, Natan Mor, Boris Yagen, and Avraham Z. Joffe. “The Role of T-2 Toxin in Experimental Alimentary Toxic Aleukia: A Toxicity Study in Cats.” Toxicology and Applied Pharmacology 43, no. 1 (January 1978): 111–24. https://doi.org/10.1016/s0041-008x(78)80036-2.

MEJ, Pronk, Schothorst RC, and H.P. van Egmond. “Toxicology and Occurrence of Nivalenol, Fusarenon X, Diacetoxyscirpenol, Neosolaniol and 3- and 15- Acetyldeoxynivalenol; a Review of Six Trichothecenes.” Home – Web-based Archive of RIVM Publications, November 7, 2002. https://rivm.openrepository.com/handle/10029/9184.

Modra, Helena, Jana Blahova, Petr Marsalek, Tomas Banoch, Petr Fictum, and Martin Svoboda. “The Effects of Mycotoxin Deoxynivalenol (DON) on Haematological and Biochemical Parameters and Selected Parameters of Oxidative Stress in Piglets.” Neuro Endocrinol Lett. 34, no. Suppl 2 (2013): 84–89.

Osborne, D.J., W.E. Huff, P.B. Hamilton, and H.R. Burmeister. “Comparison of Ochratoxin, Aflatoxin, and T-2 Toxin for Their Effects on Selected Parameters Related to Digestion and Evidence for Specific Metabolism of Carotenoids in Chickens,” Poultry Science 61, no. 8 (August 1982): 1646–52. https://doi.org/10.3382/ps.0611646.

Pande, Vivek, Nitin Kurkure, and A.G. Bhandarkar. “Effect of T-2 Toxin on Growth, Performance and Haematobiochemical Alterations in Broilers .” Indian Journal of Experimental Biology 44, no. 1 (February 2006): 86–88.

Pier , A.C., S.J. Cysewski, J.L. Richard , A.L. Baetz, and L. Mitchell. “Experimental Mycotoxicoses in Calves with Aflatoxin, Ochratoxin, Rubratoxin, and T-2 Toxin.” Proceedings, annual meeting of the United States Animal Health Association, 1976. https://pubmed.ncbi.nlm.nih.gov/1078072/.

Resanovic, Radmila, Ksenija Nesic, Vladimir Nesic, Todor Palic, and Vesna Jacevic. “Mycotoxins in Poultry Production.” Zbornik Matice srpske za prirodne nauke, no. 116 (2009): 7–14. https://doi.org/10.2298/zmspn0916007r.

Riahi, Insaf, Virginie Marquis, Anna Maria Pérez-Vendrell, Joaquim Brufau, Enric Esteve-Garcia, and Antonio J. Ramos. “Effects of Deoxynivalenol-Contaminated Diets on Metabolic and Immunological Parameters in Broiler Chickens.” Animals 11, no. 1 (January 11, 2021): 147. https://doi.org/10.3390/ani11010147.

Sreemannarayana, O., A. A. Frohlich, and R. R. Marquardt. “Acute Toxicity of Sterigmatocystin to Chicks.” Mycopathologia 97, no. 1 (January 1987): 51–59. https://doi.org/10.1007/bf00437331.

Stack, Jim, and Mike Carlson. “Fumonisins in Corn.” DigitalCommons@University of Nebraska – Lincoln, 2003. https://core.ac.uk/download/pdf/188054556.pdf.

Szathmary, C.I. “Trichothecene Toxicoses and Natural Occurrence in Hungary.” Essay. In Ueno, Y: Developments in Food Science IV. Trichothecenes, 229–50. New York: Elsevier, 1983.

Tung, Hsi-Tang, F.W. Cook, R.D. Wyatt, and P.B. Hamilton. “The Anemia Caused by Aflatoxin.” Poultry Science 54, no. 6 (November 1975): 1962–69. https://doi.org/10.3382/ps.0541962.

Tyczkowski, Juliusz K., and Pat B. Hamilton. “Altered Metabolism of Carotenoids during Aflatoxicosis in Young Chickens,” Poultry Science 66, no. 7 (July 1987): 1184–88. https://doi.org/10.3382/ps.0661184.

WHO. “Selected Mycotoxins : Ochratoxins, Trichothecenes, Ergot / Published under the Joint Sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.” World Health Organization, January 1, 1990. https://apps.who.int/iris/handle/10665/39552.

Yohannes, T., A. K. Sharma, S. D. Singh, and V. Sumi. “Experimental Haematobiochemical Alterations in Broiler Chickens Fed with T-2 Toxin and Co-Infected with IBV.” Open Journal of Veterinary Medicine 03, no. 05 (2013): 252–58. https://doi.org/10.4236/ojvm.2013.35040.

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 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.

Figure 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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Institut du Porc (IFIP), the French pork research and development institute and a key player in the French agricultural sector, has recently published its 2024 report, titled Porc par les Chiffres 2023-2024. The document provides a comprehensive overview of the global, European, and French pork industries and is a critical resource for all industry professionals.

The Global Pork Industry

The global pork industry has experienced significant changes over recent years. In 2021, global pork production reached approximately 108 million tons of carcass weight equivalent (CWE), largely driven by China’s recovery from African Swine Fever (ASF). By 2022, global production continued to rise, though at a slower pace due to the stabilization of China’s pig herd. However, the global landscape remains varied with notable regional differences.

Figure 1. Main pork exporters (in 1000 tons)*

Figure 2. Main pork importers (in 1000 tons)*

*Excluding intra-EU and intra-EUMCA-EU trade evolving: EU15 (2000-2003), EU25 (2004-2006), EU27 (2007-2013), EU28 (2014)

In Asia, China dominates pork production, contributing 47.5 million tons in 2021. Other significant producers include Vietnam, Japan, South Korea, and the Philippines. In Europe, the EU-28 collectively produced 24.6 million tons, with Germany, Spain, and France being the leading producers. In the Americas, the United States and Brazil are major contributors, with the U.S. producing 12.6 million tons and Brazil 4.4 million tons. The production in other regions like Africa and Oceania remains relatively small in comparison.

The global pork trade is equally dynamic. In 2022, the major exporters included the European Union, the United States, and Canada. Key importers were China, Japan, and Mexico. The shifting demands and production capacities have led to fluctuating trade patterns, impacting global pork prices and market stability.

Figure 3. Evolution of global pork production (GDP in 1000 tons)

Pork Industry in the European Union

The European pork industry faced a challenging year in 2022, marked by a decline in production and various economic pressures. The EU’s pork production fell by approximately 5%, equating to a loss of over 12.6 million pigs for slaughter. Germany, historically one of the largest producers, saw a significant 10% reduction in output due to ongoing economic and sanitary crises. Spain, while typically a growing market, experienced its first production decline since 2014 due to increased piglet mortality rates from health issues.

Despite these challenges, some regions showed resilience. France managed a relatively smaller production decrease of 2%, maintaining its position as a key player in the European market. The economic environment, characterized by rising inflation and high feed costs, pushed pork prices to record levels across the continent, with French pork prices ranking high in Europe, just behind Spain.

The consumption patterns within the EU also varied significantly. Countries like Denmark and Spain exhibited high per capita pork consumption rates, while others like the United Kingdom and Italy showed more moderate consumption levels. This disparity reflects both cultural preferences and economic conditions across the region.

Figure 4. Evolution of pork production in the main EU countries (tons, from a base of 100 in 2005)

The French Pork Industry

In France, the pork industry in 2022 faced a year of significant adjustments. The country produced 2.19 million tons of carcass weight equivalent, a 3% decrease from the previous year. This decline was attributed to reduced slaughter weights and lower export volumes of live pigs. Despite these challenges, France remained the third-largest pork producer in the EU, following Spain and Germany.

Regionally, pork production is concentrated in areas like Brittany and Pays de la Loire. Brittany alone accounts for a substantial portion of the national production. The distribution of pork farms across France highlights the regional specialization, with significant variations in production volumes from one region to another.

Figure 5. Suppliers to France (percentage of total imports)

French pork exports faced hurdles due to reduced demand from China, which saw a 35% drop in imports from France in 2022. However, increased sales to other Asian markets like the Philippines and Japan partially offset this decline. In terms of value, the higher pork prices helped mitigate the impact of lower export volumes, with total export values reaching 1.76 billion euros.

Figure 6. Export targets for France (percentage of total exports)

Economic and Production Challenges

The pork industry globally and within the EU faces several ongoing challenges. Rising feed costs, largely driven by global commodity price increases, have significantly impacted production costs. In Europe, the economic downturn and ongoing health crises like ASF and PRRS (Porcine Reproductive and Respiratory Syndrome) continue to challenge producers.

In France, inflation and high production costs have led to a tightening of profit margins for pig farmers. The high costs of feed and energy, coupled with lower production volumes, have made it difficult for many producers to remain profitable. The industry has responded with efforts to improve efficiency and sustainability, though these measures take time to implement and yield results.

Future Outlook

In Asia, China’s recovery from ASF will likely stabilize, but the focus will shift towards improving biosecurity and production efficiency. In Europe, the industry will need to navigate economic challenges and health crises while adapting to changing consumer preferences towards more sustainable and ethical production practices.

For France, the key to future success will lie in balancing production efficiency with market demands. Investments in technology, biosecurity, and sustainable practices will be crucial. Additionally, expanding export markets beyond traditional partners will help mitigate the risks associated with market fluctuations.

The pork industry, both globally and within the EU, is at a pivotal point. The combination of economic pressures, health challenges, and shifting market dynamics necessitates strategic adjustments. By focusing on efficiency, sustainability, and market diversification, the industry can navigate these challenges and continue to thrive in the coming years.

The report can be read in full here.

By Dr. Inge Heinzl, Editor and Technical Team, EW Nutrition

One of the biggest challenges in swine production is keeping the modern, hyperprolific sow healthy and in good shape so that she can wean large, healthy litters and maintain her high reproductive performance.

Unfortunately, sows often suffer from stress and increased systemic inflammation around farrowing and during lactation. This leads to impaired feed intake and disturbed endocrine homeostasis, negatively affecting reproductive and litter performance.

The key to increasing the efficiency of pig production is to reduce the metabolic burden of sows while maintaining the reproductive performance of high-yield sows. A deep understanding of the complex interplay between environmental factors, sow well-being, health, and productivity is necessary to implement enhanced nutritional regimens and meticulous management practices.

Why does oxidative stress occur in today’s sows?

Nowadays, hyperprolific sows produce between 30 and 40 weaned piglets per year and are at a higher risk of suffering from stress. What are the reasons?

A high number of piglets causes oxidative stress

Oxidative stress occurs when reactive oxygen species (ROS) are produced faster than the body’s antioxidant mechanisms can neutralize them and cause damage to lipids, proteins, and DNA. During gestation, the sow needs high amounts of energy to provide for the fetuses. This energy is produced in the placental mitochondria. The placenta, therefore, is a place of active oxygen metabolism during gestation and a source of oxidative stress. In hyperprolific sows, a higher number of fetuses need even more energy to grow. Consequently, ROS production and the risk for intrauterine growth retardation (IUGR) increases (Figure 1). Moreover, evidence shows that the body’s antioxidant potential is reduced in late gestation and after parturition (Szczubial, 2010), resulting in increased oxidative stress biomarkers (Yang, 2023). Increased milk production for large litters demands a substantial amount of energy, risking similar oxidative distress. Therefore, both the final phase of gestation and the subsequent lactation period are predestined for oxidative stress, which has been demonstrated by reduced TEAC (Trolox equivalent antioxidant capacity) levels during these phases (Lee et al., 2023).

Figure 1. Illustration of the effect of oxidative stress on the fetus: intrauterine growth retardation (IUGR) (adapted from Yang et al., 2023)

Heat and ambient stress also contribute

The reproductive sow produces lots of heat.  From the beginning of gestation, the sow’s thermoneutral zone decreases. This, however, does not always correspond with the ambient conditions. Especially during the last days of gestation, the discrepancy is exceptionally high as everything is prepared for the newborn piglets, which need a temperature of about 27-35°C. The sow, on the contrary, would be happy with 18-22°C. Additionally, changes around farrowing – moving to the farrowing unit, social stress, change of feed, and the preparation for parturition – exert additional stress for the sows.

Why does the inflammation level increase?

After parturition, systemic inflammation is a normal phenomenon: the reproductive organs have sustained injuries during the parturition process and require remodeling. Inflammation is a natural and desired process, to repair the tissues and return to a normal status. However, inflammation is increased in modern sows, adversely affecting their inflammatory balance. Some possible underlying reasons are:

1. The high numbers of piglets need a lot of space in the uterus, often leading to damage of the uterine tissue and an inflammatory response in the sows. Lee et al. (2023) found significantly (p<0.10) higher TNF-α concentrations in sows with litters of 15-20 piglets than in sows with 7-14 piglets. TNF-α is a biomarker of inflammation.
2. Pathogenic infections – particularly infections of the reproductive tract – can induce a prolonged or excessive inflammatory state. A further reason can be the need for more obstetric interventions in hyperprolific sows, which can injure the birth canal or the uterus.
3. Imbalanced nutrition: Excessive backfat is associated with a higher expression of proinflammatory cytokines, and feed contaminated with mycotoxins can impair the sow’s immunocompetence.

Biomarkers can inform us about the oxidative status

Biomarkers are naturally occurring molecules that help us identify diseases or physiological processes. They provide insights into the oxidative state and inflammatory processes.

Anti-oxidative biomarkers

To check the anti-oxidative capacity, the “beneficial” substances, or antioxidants, can be quantified. These substances can neutralize free radicals or be neutralized by them. Higher levels of antioxidants indicate better antioxidant capacity; when antioxidants are abundant, fewer oxidizable substances have undergone oxidation.

Examples of antioxidant biomarkers:

Total Antioxidant Capacity (T-AOC): represents the synergistic interaction effects of all antioxidants in a matrix (E.g., diet or body fluids). It’s a global measure of non-enzymatic antioxidant efficiency. Various assays, like Trolox Equivalent Antioxidant Capacity (TEAC), which measures a substance’s antioxidant capacity compared to Trolox, can measure T-AOC.

Glutathione Peroxidase (GSH-Px) belongs to the peroxidase family and converts hydrogen peroxide to water.

Catalase (CAT): scavenges ROS. Its activity can predict oxidative stress.

Superoxide Dismutase (SOD): catalyzes the dismutation of superoxide radicals to oxygen and hydrogen peroxide.

Oxidative biomarkers

Oxidative stress biomarkers, the ‘negative’ substances, can also serve as general biomarkers. These include free radicals with oxidant capacity or intermediate/final oxidation products. Ideally, their levels should be minimized.

Examples of oxidative stress biomarkers:

Thiobarbituric acid reactive substances (TBARS): to measure lipid peroxidation products in cells, tissues, and body fluids.

Reactive oxygen species (ROS) or free radicals: unstable, oxygen-containing molecules that react with other molecules in a cell. They might damage DNA, RNA, and proteins and cause cell death. Hydrogen Peroxide (H₂O₂) is a ROS produced during normal cellular metabolism, which causes oxidative damage at excessive levels.

Malondialdehyde (MDA): a final product of oxidative fat degradation and, therefore, a biomarker for lipid peroxidation.

Pro-inflammatory biomarkers

Like oxidative stress, the interplay between pro- and anti-inflammatory signals helps develop the proper immune response for the appropriate duration.

Examples of Pro-inflammatory biomarkers or molecules produced in the case of inflammation:

• Plasma Adenosine Deaminase (ADA-1 and ADA-2): involved in immune regulation, with ADA-1 inhibiting pro-inflammatory responses and ADA-2 supporting immune cell functions.
• Interleukins (IL-1α and IL-1β), IL-6: IL-1α and IL-1β are associated with inflammatory diseases, IL-6: is produced during inflammation and acute-phase response.
• Tumor Necrosis Factor α (TNF-α): endogenous pyrogen that induces fever and promotes inflammation.
• C-reactive Protein (CRP): liver-produced acute-phase protein responding to inflammation.

Procalcitonin (PCT) is produced by the liver during infections and helps detect bacterial infections.

Examples of anti-inflammatory substances – the “good ones”:

• Interleukines – IL-4, IL-10: inhibit the function of the macrophages and act, therefore, anti-inflammatory
• Cortisol: anti-inflammatory and immune-suppressive
• ACTH: stimulates the production and release of cortisol

Higher stress or infection level lowers performance in sows and piglets

As mentioned, hyperprolific sows suffer from higher oxidative stress, especially during late gestation, parturition, and lactation. Additionally, systemic inflammation occurs to repair the injured tissues to facilitate the healing of the birth canal and remodeling of the uterus to establish the subsequent pregnancy. To this purpose, an inflammatory cascade, triggered by the injuries due to gestation and parturition, involves the release of critical (pro-inflammatory) mediators such as TNF-α and IL-6, leading to the activation of acute phase proteins.

After triggering inflammatory pathways, anti-inflammatory pathways must also be activated to reestablish homeostasis in the reproductive organs (Serhan & Chiang, 2008). Alterations at the onset of anti-inflammatory pathways and exacerbated activation and maintenance of inflammatory pathways can lead to uncontrolled inflammation and the onset of reproductive disease in sows (Kaiser et al., 2018), as well as reduced feed intake and insufficient milk production, resulting in poorly growing piglets and lower weaning weights or piglets suffering from clinical infectious diseases such as diarrhea. If possibly homeostasis cannot be restored, the sow is at risk of contracting diseases like post-partum dysgalactia syndrome (PPDS), lameness, and impaired fertility.

Targeted use of polyphenols can mitigate inflammation and improve the oxidative status of sows

There are several experiments showing the beneficial effects of natural compounds. Especially polyphenols, disposing of phenyl rings and two or more hydroxyl substituents, are perfect radical scavengers and proven antioxidants (Chen, 2023). Phytogenic substances that have anti-inflammatory effects can be found in the families of polyphenols as well as terpenoids, flavonoids, saponins, and tannins (Bunte et al., 2019; Ge et al., 2022; Ginwala et al., 2019; Santos Passos et al., 2022; Ambreen and Mirza, 2020).

Here are some examples showing the beneficial effects of phytochemicals:

1. Primiparous sows fed with Moringa oleifera leaf meal, rich in polyphenols, saponins, and tannins, illustrate the potential of phytomolecules: serum levels of T-AOC (total anti-oxidative capacity), were increased in late gestation and during lactation, while MDA was reduced. Additionally, piglets that received Moringa oleifera meal showed the highest serum CAT and SOD activities. The meal significantly decreased the farrowing length and number of stillbirths, while there was an increasing trend in the number of live‐born piglets (Sun et al., 2020).
2. The polyphenol Daidzein, a member of the class of compounds known as isoflavones (200 mg/kg during gestation), increased the total antioxidant capacity (T-AOC) and the activities of glutathione peroxidase and superoxide dismutase. Additionally, it elevated the level of immunoglobulin G and increased the number of piglets born and born alive per litter (Li et al., 2021).
3. Glycitein, a polyphenol occurring in the isoflavone fraction of soy products, applied during late gestation and lactation increased the total antioxidant capacity and SOD activity during the first 18 days of lactation and the CAT and GSH-Px activity in mid-lactation. Plasma MDA level was reduced from late gestation to the 18^th day of lactation. The enhanced oxidative status of the sow resulted in a higher daily gain of the piglets and a higher weaning weight of the litter (Hu et al., 2015).
4. Meng et al. (2018) tested Resveratrol (300 mg/kg), a stilbenes polyphenol, in sows from day 20 of gestation until farrowing. They saw noticeably higher GSH-Px, SOD, and CAT activities, as well as lower contents of MDA and H₂O₂ in the placental tissue, improving the antioxidant status of sows and piglets.
5. Xu et al. (2022) fed silymarin to sows in late gestation. They observed that IL-1ß concentration in the blood sample on the 18^th day of lactation was reduced in the supplemented group. The altered fecal microbiota was associated with variations in inflammatory factors, suggesting that silymarin modulates microbiota in the gut and may improve the health of lactation sow.

Phytochemicals support sows against oxidative and inflammatory stress

The above-presented examples show that phytochemicals, particularly those developed to have a potent anti-inflammatory and anti-oxidative capacity, have a high potential to alleviate oxidative stress in pregnant and lactating sows and reduce inflammation when applied in sow diets. Consequently, a broader use of these natural substances should be considered to reduce the metabolic burden of sows and increase the efficiency of pig production.

References:

Ambreen, Madieha, and Safdar Ali Mirza. “Evaluation of Anti-Inflammatory and Wound Healing Potential of Tannins Isolated from Leaf Callus Cultures of Achyranthes Aspera and Ocimum Basilicum.” Pak J Pharm Sci . 33, no. 1 (January 2020): 361–69.

Bunte, Kübra, Andreas Hensel, and Thomas Beikler. “Polyphenols in the Prevention and Treatment of Periodontal Disease: A Systematic Review of in Vivo, Ex Vivo and in Vitro Studies.” Fitoterapia 132 (January 2019): 30–39. https://doi.org/10.1016/j.fitote.2018.11.012.

Chen, Jun, Zhouyin Huang, Xuehai Cao, Tiande Zou, Jinming You, and Wutai Guan. “Plant-Derived Polyphenols in Sow Nutrition: An Update.” Animal Nutrition 12 (March 2023): 96–107. https://doi.org/10.1016/j.aninu.2022.08.015.

Ge, Jiamin, Zhen Liu, Zhichao Zhong, Liwei Wang, Xiaotao Zhuo, Junjie Li, Xiaoying Jiang, Xiang-Yang Ye, Tian Xie, and Renren Bai. “Natural Terpenoids with Anti-Inflammatory Activities: Potential Leads for Anti-Inflammatory Drug Discovery.” Bioorganic Chemistry 124 (July 2022): 105817. https://doi.org/10.1016/j.bioorg.2022.105817.

Ginwala, Rashida, Raina Bhavsar, De Gaulle Chigbu, Pooja Jain, and Zafar K. Khan. “Potential Role of Flavonoids in Treating Chronic Inflammatory Diseases with a Special Focus on the Anti-Inflammatory Activity of Apigenin.” Antioxidants 8, no. 2 (February 5, 2019): 35. https://doi.org/10.3390/antiox8020035.

Hu, Y. J., K. G. Gao, C. T. Zheng, Z. J. Wu, X. F. Yang, L. Wang, X. Y. Ma, A. G. Zhou, and Z. J. Jiang. “Effect of Dietary Supplementation with Glycitein during Late Pregnancy and Lactation on Antioxidative Indices and Performance of Primiparous Sows1.” Journal of Animal Science 93, no. 5 (May 1, 2015): 2246–54. https://doi.org/10.2527/jas.2014-7767.

Kaiser, Marianne, Stine Jacobsen, Pia Haubro Andersen, Poul Bækbo, José Joaquin Cerón, Jan Dahl, Damián Escribano, Peter Kappel Theil, and Magdalena Jacobson. “Hormonal and Metabolic Indicators before and after Farrowing in Sows affected with postpartum Dysgalactia Syndrome.” BMC Veterinary Research 14, no. 1 (November 7, 2018). https://doi.org/10.1186/s12917-018-1649-z.

Lee, Juho, Hyeonwook Shin, Janghee Jo, Geonil Lee, and Jinhyeon Yun. “Large Litter Size Increases Oxidative Stress and Adversely Affects Nest-Building Behavior and Litter Characteristics in Primiparous Sows.” Frontiers in Veterinary Science 10 (August 22, 2023). https://doi.org/10.3389/fvets.2023.1219572.

Li, Yan, Guoru He, Daiwen Chen, Bing Yu, Jie Yu, Ping Zheng, Zhiqing Huang, et al. “Supplementing Daidzein in Diets Improves the Reproductive Performance, Endocrine Hormones and Antioxidant Capacity of Multiparous Sows.” Animal Nutrition 7, no. 4 (December 2021): 1052–60. https://doi.org/10.1016/j.aninu.2021.09.002.

Meng, Qingwei, Tao Guo, Gaoqiang Li, Shishuai Sun, Shiqi He, Baojing Cheng, Baoming Shi, and Anshan Shan. “Dietary Resveratrol Improves Antioxidant Status of Sows and Piglets and Regulates Antioxidant Gene Expression in Placenta by Keap1-Nrf2 Pathway and SIRT1.” Journal of Animal Science and Biotechnology 9, no. 1 (April 20, 2018). https://doi.org/10.1186/s40104-018-0248-y.

Santos Passos, Fabiolla Rocha, Heitor Gomes Araújo-Filho, Brenda Souza Monteiro, Saravanan Shanmugam, Adriano Antunes Araújo, Jackson Roberto Almeida, Parimelazhagan Thangaraj, Lucindo José Júnior, and Jullyana de Quintans. “Anti-Inflammatory and Modulatory Effects of Steroidal Saponins and Sapogenins on Cytokines: A Review of Pre-Clinical Research.” Phytomedicine 96 (February 2022): 153842. https://doi.org/10.1016/j.phymed.2021.153842.

Serhan, C N, and N Chiang. “Endogenous Pro‐resolving and Anti‐inflammatory Lipid Mediators: A New Pharmacologic Genus.” British Journal of Pharmacology 153, no. S1 (March 2008). https://doi.org/10.1038/sj.bjp.0707489.

Sun, Jia‐Jie, Peng Wang, Guo‐Ping Chen, Jun‐Yi Luo, Qian‐Yun Xi, Geng‐Yuan Cai, Jia‐Han Wu, et al. “Effect of Moringa Oleifera Supplementation on Productive Performance, Colostrum Composition and Serum Biochemical Indexes of Sow.” Journal of Animal Physiology and Animal Nutrition 104, no. 1 (October 30, 2019): 291–99. https://doi.org/10.1111/jpn.13224.

Szczubiał, M. “Changes in Oxidative Stress Markers in Plasma of Sows during Periparturient Period.” Polish Journal of Veterinary Sciences, March 3, 2020, 185–90. https://doi.org/10.24425/pjvs.2020.132764.

Xu, Shengyu, Xiaojun Jiang, Xinlin Jia, Xuemei Jiang, Lianqiang Che, Yan Lin, Yong Zhuo, et al. “Silymarin Modulates Microbiota in the Gut to Improve the Health of Sow from Late Gestation to Lactation.” Animals 12, no. 17 (August 26, 2022): 2202. https://doi.org/10.3390/ani12172202.

Yang, Xizi, Ruizhi Hu, Mingkun Shi, Long Wang, Jiahao Yan, Jiatai Gong, Qianjin Zhang, Jianhua He, and Shusong Wu. “Placental Malfunction, Fetal Survival and Development Caused by Sow Metabolic Disorder: The Impact of Maternal Oxidative Stress.” Antioxidants 12, no. 2 (February 2, 2023): 360. https://doi.org/10.3390/antiox12020360.

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.

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

Author: Judith Schmidt, Product Manager On Farm Solutions

Alarm in the gut! Horses have a susceptible digestive system that can quickly become unbalanced. Intestinal disorders in horses are usually associated with colic. Many factors can be responsible for intestinal issues. Have you ever thought about mycotoxins? What can horse owners do to support their horse´s gut health?
The equine stomach is not robust at all. Depending on their age and use, more than half of all horses suffer from stomach pain. Their digestive system is very sensitive and very different from that of other mammals: Horses cannot vomit and often suffer from severe abdominal pain, diarrhea, or cramps if they overeat or ingest spoiled feed.

The horse´s digestive system is complex and sensitive

The horse´s stomach has a relatively small capacity of around twelve to fifteen liters. Depending on the feed’s consistency and composition, it remains in the stomach for around one to five hours before it is pressed through the stomach outlet (pylorus) into the small intestine. The horse´s entire intestine is about ten times its body length.

Figure 1: The horse’s digestive tract

The horse´s gastrointestinal tract is a complex network, reacting extremely sensitively to changes and, therefore, highly susceptible to disorders. It essentially consists of the head intestine (lips, oral cavity, teeth, and esophagus), stomach (blind pouch, fundus, and stomach outlet), small intestine (duodenum, jejunum, and ileum), and large intestine (caecum, colon and rectum). Each section plays a crucial role in the digestive process; any disruption can lead to health issues. Understanding this structure is key to maintaining a horse’s digestive health.

Digestive disorders can have various reasons

Intestinal problems in horses can stem from diverse causes, often a complex interplay of multiple factors. By understanding these causes more deeply, horse owners can be better equipped to prevent and manage these issues. In the following, we delve into several of these causes.

1.   Too long time between the feedings

Usually, a feeding break should be at most four to six hours, as, in nature, a horse is busy eating for at least 18 hours a day. In contrast to humans, who produce stomach acid only after food intake, the horse’s stomach produces gastric acid around the clock. The continuous intake of roughage, intensive chewing, and high saliva production (a horse produces 5 to 10 L of saliva per day) is, therefore, essential to protect the stomach mucosa by neutralizing excess gastric acid.

A too-long time between feedings and, therefore, no saliva production leads to an accumulation of gastric acid in the stomach. Four hours without roughage can already cause inflammation of the mucosa and probably ulcers.

2.   Excessive amounts of concentrated feed

Excessive amounts of concentrates such as wheat or rye, conditioned by less chewing activity, increase gastric acid and histamine production, and the stomach lining can be attacked. Also, in this case, the development of stomach ulcers is possible.

Furthermore, the possibly resulting hyperacidity of the organism can lead to malfunctions of the organs, the skin, and the hooves.

3.   Stress

Stress can also lead to a higher production of gastric acid and, therefore, to gastric ulcers. The horse is a flight animal.  When it is under stress, it prepares for the impending escape, and the muscles are preferably supplied with blood, resulting in a lower blood flow to the mucous membranes. Furthermore, the rising cortisone level reduces the hydrochloric acid-suppressing prostaglandin E. As a result, more stomach acid is produced, irritating the gastric mucosa.

Stress can be triggered, e.g., by transportation, competitions, training, a change of house, a new rider, unsuitable equipment, or poor posture.

4.   Dental diseases

The teeth are essential for digestion. When feed is chewed, it is broken down and mixed with saliva. Chipped teeth cannot chew well, and the feed is not sufficiently salivated or crushed, which has a detrimental effect on digestion.

For this reason, an expert vet should check the horse´s teeth at least once a year.

5.   Administration of painkillers/medication

As with humans, long-term medication administration can promote the formation of stomach ulcers. For this reason, it is essential to ensure that horses are fed a gentle diet on the stomach, especially when using oral pain therapy, and to add stomach protection if necessary.

6. Endotoxins

If pathogens such as E. coli or clostridia proliferate extremely or are killed by an antibiotic, endotoxins can be released. These toxins can cause transformation or inflammation of the gut mucosa. In drastic cases, whole areas of the mucosa can die off. 

7. Mycotoxins – the hidden danger in horse feed

Mycotoxins in plants and horse feed are a common but often unnoticed danger to horses’ health. Mycotoxins are natural, secondary metabolites of molds that have a toxic effect on humans and animals and can trigger mycotoxicosis. Contaminated feed can severely affect the horse’s health and, in the worst case, lead to death.

Over 90 % of the world´s feed production is estimated to be contaminated with at least one mycotoxin (see also Global Mycotoxin Report 2023, EW Nutrition. The intake of mycotoxins via hay, grain, silage, or compound feed can hardly be avoided. Mycotoxins are an increasing problem for all horse owners. Scientific studies show that the mycotoxins DON and ZEA are most frequently found in horse feed and, therefore, are also frequently detected in sports horses’ urine and blood samples.

Due to the highly toxic metabolic products, feed contaminated with molds can lead to severe liver and kidney diseases in horses, affect fertility, trigger colic, and promote digestive issues (diarrhea and watery stools).

Figure 2: Mycotoxins and their impact on horses

How to protect the horse from mycotoxins?

The first measure against the ingestion of mycotoxins is prevention. Correct pasture management and adequate barn and feed hygiene can contribute to preventing the ingestion of toxins.

However, despite the best prophylactic measures, it is impossible to prevent mycotoxin contamination of feed completely. As mycotoxins are not visible, analyzing the feed regarding mycotoxin contamination is recommended.

To protect your horse from mycotoxins, EW Nutrition developed MasterRisk, a tool for evaluating the risk of mycotoxins. Additionally, EW Nutrition has developed a complementary feed specifically for your horse´s needs in the form of granules. The sophisticated formulation of “Toxi-Pearls” is designed to bind mycotoxins and mitigate the adverse effects of mycotoxin contamination.

The pearls contain a mixture of mycotoxin binder, brewer’s yeast, and herbs:

• The contained mycotoxin binder effectively controls the most important feed myco- and endotoxins. It additionally supports the liver and immune system and strengthens the intestinal barrier.
• Brewer´s yeast supports the natural strength of the gastrointestinal tract. Due to its high natural content of beta-glucans and mannan-oligosaccharides (MOS), unique surface structure, and the associated high adsorption power, brewer´s yeast has a prebiotic effect on the intestinal microbiome.
• The additional unique herbal mixture consists of the typical gastrointestinal herbs oregano, rosemary, aniseed, fennel, and cinnamon. The processed beetroot is a true all-rounder. Literature shows that it has an antioxidant effect and strengthens the immune system. It also promotes bile secretion and, therefore, supports fat digestion.

Conclusion

The horse’s digestive tract is highly sensitive and must be supported by all means. Besides failures in management, such as too long breaks between feedings or too high amounts of feed concentrate, mycotoxins present a high risk in horse nutrition. To prevent horses from intestinal issues, feed and stress management, dental care, and medication in the case of disease must be optimized. Particular attention should be paid to possible mycotoxin contamination. Effective toxin risk management, which consists of analysis, risk evaluation, and adequate toxin risk-managing products, should be implemented.

Part 2: Beak/mouth lesions

by Technical Team and Inge Heinzl, Editor EW Nutrition

The second part of this series will focus on oral lesions as signs of mycotoxin exposure. In this segment, we will delve into the appearance and development of oral lesions, their specific locations based on the type of mycotoxin, and how toxin levels and duration of exposure impact these lesions.

A bit of history: oral lesions in poultry and their association with mycotoxin exposure

Exposure to trichothecenes, a specific group of mycotoxins that includes T-2 toxin and scirpenols- such as monoacetoxyscirpenol (MAS), diacetoxyscirpenol (DAS), and triacetoxyscirpenol, has been associated with oral lesions since the early studies related with mycotoxins:

• After reports of toxicosis in farm animals, Bamburg’s group (1968) aimed to isolate the toxins produced by Fusarium tricintum, then considered the most toxic fungus found in moldy corn in Wisconsin (USA). Their experiments led to the discovery of the T-2 toxin, named after the strain of F. tricintum from which it was isolated. Today, we know that this fungus was wrongly identified; it was F. sporotrichioides (Marasas et al., 1984). However, the toxin remained known as T-2.
• Wyatt’s group (1972) already described yellowish-white lesions in the oral cavity of commercial broilers in a case report from 1972. The birds also presented lesions on the feet, shanks, and heads, which raised the possibility of contact with the toxin from the litter.
• In some of the earliest experimental works regarding T-2 toxin in poultry, Christensen (1972) noted the development of oral necrosis in turkey poults consuming increasing levels of feed invaded by tricintum; also Wyatt (1972) found a linear increase in lesion size and severity with increasing toxin concentrations of T-2 in broilers, starting with 1 ppm. He noted that oral lesions occurred without exception in all birds receiving T-2 toxin.
• Later, Chi and co-workers (1977) tested what later were considered sub-acute levels of T-2 in broiler chickens, finding oral lesions from 0.4 ppm after 5 to 6 weeks of exposure. At higher levels, the lesions appeared after two weeks. In the same year, Speers’ group (1977) concluded that adult laying hens are more tolerant to T-2 than young chicks and also found that another mycotoxin can produce oral lesions in poultry: monoacetoxyscirpenol (MAS).
• Fast forward, scientific research continued and the effects of T-2 and scirpenols, either alone or in combinations, on performance and oral lesions in poultry are today well known, as studied by Kubena et al. (1989), Ademoyero & Hamilton (1991), Kubena et al. (1994), Diaz et al. (1994), Brake et al. (2000), Schuhmacher-Wolz et al. (2010), Verma & Swamy (2015), Vaccari (2017), and reviewed by Sokolovic et al. (2008), Minafra et al. (2018), Puvača & Ljubojević Pelić (2023), and Vörösházi et al. (2024).

What are oral lesions and how do they develop?

Oral lesions caused by feed contaminated by T-2 toxin or scirpenols first occur as yellow plaques that develop into raised yellowish-gray crusts with covered ulcers (Hoerr et al., 1982). They also have been described as white in color and sometimes caseous in nature, as well as round and small, pin-point-sized, or large sheets covering a wider part of the mouth (Wyatt et al., 1972; Ademoyero and Hamilton, 1991).

Under the microscope, the lesions show a fibrinous surface layer and intermediate layers with invaginations full of rods and cocci, suggesting that the surrounding microbiota quickly colonizes the lesion. Inflammation immediately ensues as Wyatt’s team (1972) found the underlying tissues filled with granular leukocytes.

Why do T-2 toxins and other trichothecenes cause such lesions?

T-2 toxin and other trichothecenes are known for their caustic nature (evidenced by studies of Chi and Mirocha, 1978; Marasas et al., 1969), and for incidents involving accidental exposure by laboratory personnel (Bamburg et al., 1968, cited in Wyatt et al., 1972).

Induction of necrosis has been proposed as the main toxicity effect based on in vitro experiments on human skin fibroblast models. The findings were a reduction of ATP production in the cell line together with disruption of mitochondrial DNA (mtDNA) but without an increase in reactive oxygen species (ROS) or activity of caspase-3 and caspase-7, which would be the case for apoptosis (Janik-Karpinsa et al., 2022). A further study (Janik-Karpinsa et al., 2023) found that T-2, on the same cell line, reduced the number of mtDNA copies, damaging several genes and hindering its function; consequently, ATP production is inhibited, and cell necrosis ensues.

Meanwhile, an inflammatory response is triggered, and the lesions are colonized by the surrounding microbial flora (Wyatt et al., 1972). Supporting this notion, Hoerr et al. (1981) observed no mouth lesions after directly administering toxins via crop gavage. Enterohepatic recirculation, facilitating the return of toxins to the oral cavity through saliva, can amplify their toxic effects (Leeson et al., 1995).

Oral lesions depend on…

…the toxin

Oral lesions vary depending on the type of toxin involved. The location of lesions is influenced by the specific mycotoxin in the feed. For instance, research by Wyatt et al. (1972) revealed that with T-2 toxin, lesions initially manifest on the hard palate and along the tongue’s margins. Over two weeks, these lesions progress to affect the lingual papillae at the tongue’s root, the underside of the tongue, and the inner side of the lower beak near the midline.

In contrast, Ademoyero and Hamilton (1991) found that scirpenols present a different pattern. A study including 4 mycotoxins at 5 different levels found, after three weeks of exposure, that the lesions caused by triacetoxyscirpenol (TAS) predominantly occurred in the angles of the mouth (53% of the birds in the study), sparing the tongue. On the other hand, diacetoxyscirpenol (DAS) primarily induces lesions inside the upper beak (shown 47% of the broilers), followed by the inside of the lower beak (in 32% of the birds). The lesion distribution for scirpentriol mirrors that of TAS, while monoacetoxyscirpenol (MAS) resembles DAS in its impact.

Chi and Mirocha (1978) conducted a comparative analysis of lesions caused by T-2 toxin and DAS (both 5 ppm). They observed that the severity of DAS-induced lesions was higher, leading to difficulties in mouth closure for some chicks due to encrustations in the mouth angles.

…the contamination level

Different findings regarding the dose dependency of the lesions are available. Wyatt et al. (1972) (Figure 1) showed a relationship between the lesion size and the toxin level. A clear relationship between the severity and incidence of lesions and the amount of T-2 toxin was also demonstrated by Chi et al. (1977) and Speers et al. (1976). This linear relationship in the case of T-2 toxin could be confirmed for the scirpenols TAS, STO, MAS, and DAS by Ademoyero and Hamilton (1991). They demonstrated a distinct dose-response relationship in a trial with the scirpenols STO, TAS (at 5 levels between 0-8 µg/g), MAS, and DAS (at 5 levels between 0-4 µg/g).

Sklan et al. (2001) tested T-2 toxin at more likely levels (0, 110, 530, and 1,050 ppb) in male chickens and found lesions in 90% of the chickens fed 500 ppb T-2 and in 100% of the ones fed 1,000 ppb of T-2 after 10 to 15 days; the higher dosage provoked the lesions of higher severity. When feeding 100 ppb of T-2, mild lesions appeared in 40% of the chickens after 25 and 35 days. Another group led by Sklan (2003) studied four groups of 12 one-day-old male turkey poults fed mash diets with 0 (control), 241, 485, or 982 ppb T-2 toxin for 32/33 days. Feed intake and feed efficiency were not affected, but oral lesions were apparent on day 7. The severity of the lesions plateaued after 7–15 days, and the lesion score was dose-related (see Figure 2). In the same trial, they also tested DAS (0, 223, 429, or 860 ppb) and found a similar dose relationship.

Figure 2: Lesion scores in poults fed T-2 toxin at different inclusion rates and lengths of exposure (Sklan et al., 2003)

A different result is found in the trial conducted by Hoerr et al. (1982), who observed lesions 2-4 days after initiating toxin exposure (T-2 toxin and DAS; 4 and 16 ppm for 21 days) and comparable lesions when feeding 50, 100, or 300 ppm of the same toxins for 7 days. They asserted that the toxin concentration did not influence the time to onset of lesions nor their severity. Most research, however, shows a clear dose-response relation.

…the duration of exposure

On one hand, chronic exposure to low levels of toxins often requires a specific duration before noticeable effects emerge. And on the other hand, symptoms may also diminish due to hormesis, an adaptive response of the organism to moderate, intermittent stress.

With high toxin levels, lesions appear very soon after exposure. For example, Diaz et al. (1994) exposed hens to a diet containing 2 mg DAS/kg feed, finding lesions in 40% of the birds after only 48 h of exposure. Chi and Mirocha (1978) noted lesions after five days with a T-2 level of 5 ppm. At a comparable level (4 ppm), Chi et al. (1977) reported lesions emerging in the second week of exposure, with nearly 75% of chicks experiencing oral lesions by the third week. Sklan et al. (2003) saw lesions already on day 7 when feeding T-2 toxin or DAS at 1 ppm.

When testing lower levels (200 ppb), Sklan et al. (2001) found lesions after 10 days. They became more severe after 15 to 20 days and then, their severity decreased. Hoerr et al. (1982) also confirmed this by reporting that the number and size of the lesions increased until day 14 but decreased thereafter. Both studies confirm the phenomenon of hormesis.

… animal factors

In general, lesions appear with lower levels of toxins in broilers compared with layers and in layers compared with breeders. Turkeys are also less sensitive than broilers (Puvača & Ljubojević Pelić (2023).

Age also has an influence: young birds usually still have a maturing immune system, and the detoxification processes might not be entirely in place. However, their feed intake is lower and for this reason, in studies like Wang and Hogan (2019), higher impact of mycotoxins is found in older chicks.

Furthermore, additional stress factors influence the impact of mycotoxins in animals. Stress factors are cumulative and, when different factors concur, the severity of mycotoxin effects can increase.

Are oral lesions key indicators for implementing effective toxin risk management?

Oral lesions are painful for the animals, distract them from eating, and deteriorate growth performance. Often they are related with mycotoxins; however, when they appear, an investigation of different factors should take place, including mycotoxin analysis, as oral lesions may have other causes. Some of the known causes of oral lesions in poultry are also very fine feed particle size, deficiency of Vitamins A, E, B6 and Biotin, excessive levels of copper sulphate, and some parasite infections.

This article aimed to help with the differential diagnosis by providing a summary of the knowledge we have about the type and shape of the lesions related to mycotoxin contamination, which can help on a differential diagnosis. Checking the feed for mycotoxins and implementing effective toxin management helps prevent their negative effects, keeps the animals healthy, and contributes to animal welfare and, consequently, performance.

References

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Over the past decade, the food industry witnessed a surge in the popularity of alternative proteins, driven by growing consumer awareness of environmental issues, animal welfare concerns, and health considerations. However, recent trends indicate a decline in both consumer interest and investment in alternative proteins. This article explores the challenges in producing viable replacements for traditional meat, the status of sales investments, and the global outlook for protein consumption.

Figure 1. Uncompetitive prices of artificial meat are a critical factor in the market downturn

Challenges in artificial meat production

Producing artificial meat, also known as cultured or lab-grown meat, has been widely hyped and substantially funded over the last decade. However, many challenges remain on several levels.

Cell Culturing and Growth

Cell Source: Obtaining high-quality animal cells is crucial. Researchers typically use muscle cells (myocytes) from animals like cows, pigs, or chickens.

Cell Proliferation: Culturing cells in the lab requires precise conditions, including the right nutrients, temperature, and oxygen levels. Ensuring rapid and efficient cell growth is essential.

Scaffold Development

3D Structure: Creating a meat-like texture involves growing cells on a scaffold that mimics the natural 3D structure of muscle tissue. Developing suitable scaffolds is challenging.

Biocompatibility: The scaffold material must be biocompatible and support cell attachment, proliferation, and differentiation.

Nutrient Supply

Medium Formulation: The nutrient-rich medium used to feed the cells must provide essential amino acids, vitamins, and minerals. Designing an optimal medium is complex.

Cost Efficiency: Developing cost-effective and sustainable nutrient solutions is critical for large-scale production.

Scaling Up Production

Bioreactors: Moving from small-scale lab experiments to large-scale bioreactors is a significant challenge. Bioreactors must maintain consistent conditions for cell growth.

Energy Consumption: Scaling up production while minimizing energy consumption and environmental impact is essential.

Flavor and Texture

Taste and Aroma: Artificial meat would be expected to taste and smell like traditional meat. Achieving the right flavor profile is an ongoing challenge.

Texture: Mimicking the texture of different meat cuts (e.g., steak, ground beef) requires precise engineering.

Safety and Regulation

Food Safety: Ensuring that cultured meat is safe for consumption is critical. Contamination risks, such as bacterial growth, must be minimized.

Regulatory Approval: Cultured meat faces regulatory hurdles related to labeling, safety assessments, and consumer acceptance.

Cost Reduction

High Initial Costs: Currently, producing artificial meat is expensive due to research, development, and infrastructure costs. Reducing these costs is essential for commercial viability.

Acceptance and Perception

Consumer Perception: Convincing consumers that cultured meat is a viable and ethical alternative to traditional meat remains a challenge.

Cultural and Social Factors: Cultural preferences and traditions play a role in consumer acceptance.

Challenges in alternative protein production

As opposed to artificial meat, which still involves animal cells, alternative proteins usually designate plant-based meat imitations. However, producing alternative proteins comes with its own set of challenges.

Diverse protein sources are one challenge that is not easy to overcome. It turns out, it is quite hard to replicate the availability, as well as the diversity of health and nutritional benefits of traditional meat. While plant-based proteins have made significant progress, there’s still room for improvement in terms of variety and availability.

Procuring the technology needed to extract protein efficiently and sustainably is another hurdle. Innovations in extraction methods are essential for scaling up alternative protein production.

Lower nutritional benefits of alternative proteins represent a major hurdle. Not only is it hard to mimic the entirety of meat’s benefits, but plant nutritional values are notoriously fickle depending on region, soil, production type, season, and so on.

Flavor and texture remain extremely elusive. Contenders are closer to a meat-feel than before, yet this remains a major factor skewing negative in consumer perception.

Figure 2: Alternative protein producers have been unable to replicate the taste and texture of traditional meat

Scaling and Supply Chain Challenges are getting more, not less complicated. Achieving affordability at scale is essential for alternative meats to compete with traditional meat products. Additionally, ensuring a robust and efficient supply chain for alternative proteins is a concern that has not found a sustainable solution.

The Status of Alternative Protein Sales and Investment

Sales Trends

According to the Plant Based Foods Association (PBFA), overall plant-based meat units have declined by 8.2% in 2022, while dollar sales decreased by 1.2% following a significant growth phase in previous years. Similarly, Euromonitor International reported that global sales of plant-based meat substitutes grew by only 1% in 2022, a stark contrast to the double-digit growth rates seen earlier in the decade.

Beyond Meat, one of the market leaders, reported a decline in net revenues of 13.9% in the third quarter of 2022 compared to the same period in 2021. This decline reflects broader market trends where consumer enthusiasm appears to be waning.

Figure 3. Rabobank indicates a downward trend in both sales and investments

Investment Trends

Investment in alternative protein startups also shows signs of slowing, with funding of sustainability food and agriculture startups dramatically declining (see Figure 2 below). According to the Good Food Institute (GFI), global investment in alternative proteins dropped 42% year-over-year to $1.2 billion in 2022, a significant decrease from the $3.1 billion invested in 2021.

The financial challenges faced by some high-profile companies have led to increased caution among investors. For instance, Beyond Meat and Oatly have both experienced substantial stock price declines, leading to a reassessment of the market’s growth potential.

Figure 4: 2023 funding variation for climate and sustainability technologies

Factors Contributing to the Decline

Market Saturation and Competition

The initial surge in demand led to rapid market saturation. Numerous companies entered the market, resulting in intense competition and a proliferation of products. This saturation has made it difficult for individual brands to maintain market share and grow sales.

In the US, for example, plant-based milk remains the largest category, while plant-based meat and seafood sales declined substantially in 2023.

Consumer Preferences and Expectations

While early adopters of alternative proteins were driven by ethical and environmental considerations, mainstream consumers remain price-sensitive and often prefer traditional meat products (to the extent they may choose smaller meat portions over alternative proteins). Additionally, taste and texture remain critical factors. Despite advancements, many consumers still find plant-based alternatives lacking in these areas.

Figure 5: Seems fake? Consumers find it hard to believe the claims of identical taste and texture in non-meat products

Economic Factors

The global economic downturn and inflation have impacted consumer spending power. As a result, many consumers are prioritizing affordability over sustainability, leading to reduced purchases of typically more expensive plant-based products.

Regulatory and Supply Chain Challenges

Regulatory hurdles and supply chain disruptions have also played a role. The COVID-19 pandemic exacerbated supply chain issues, affecting the availability and cost of raw materials needed for alternative protein production.

Conclusion: Global Outlook for Protein and Alternative Proteins

Traditional meat consumption continues to grow, particularly in emerging markets. According to the Food and Agriculture Organization (FAO), global meat consumption is projected to increase by 14% by 2030, driven by population growth and rising incomes in developing countries.

Advances in food technology, such as precision fermentation and cell-cultured meat, offer the potential to create products that more closely mimic traditional meat. However, the recent decline in interest in alternative proteins reflects a complex interplay of market saturation, economic factors, and consumer preferences.

High prices, lack of scalability, sustainability concerns, and an inability to recreate the nutritional content, texture, and taste of meat are hurdles that cannot be easily overcome. Instead, perhaps a more accessible long-term solution might be improved sustainability in the livestock sector, accompanied by continued innovation and improvements in the production of both traditional protein and alternative proteins.