As the World Mycotoxin Forum Connects event approaches in May 2022, Trouw Nutrition, Nutreco's animal nutrition division, is spotlighting approaches that integrate gut health and immunity into a holistic mycotoxin management strategy. Combining tools to protect gut health, support bird immunity and defend against pathogens, antigens and endotoxins can help support flock performance even as emerging mycotoxin threats persist.

During a pre-conference virtual presentation, Swamy Haladi, DVM, PhD, Global Programme Manager Mycotoxin Risk Management at Trouw Nutrition shared recent research exploring the effects of multiple mycotoxins on bird health and performance. Dr. Haladi also discussed how an integrated approach that goes beyond binders to support birds' gut health and immunity can help enhance flock health. Following are excerpts from Dr. Haladi's presentation.

Mycotoxin contamination – considering the consequences

While more than 600 mycotoxins are recognized today, common mycotoxins in poultry production include the genera Fusarium (trichothecenes like deoxynivalenol (DON) and T-2 toxin as well as non- trichothecenes such as Zearalenone, and Fumonisins), Aspergillus (Aflatoxins and Ochratoxins) and Penicillium (Ochratoxins). An extensive body of research links these mycotoxins to adverse effects on breeders', broilers' and layers' organs and systems. For example, T-2 and HT-2 toxins have been linked to mucosal legions in the mouth. Aflatoxins, Fumonisins and Trichothecenes have been linked to problems with liver functioning and hepatoxicity. Ochratoxins have been linked to kidney issues and renal toxicity. And, in breeders, mycotoxins have been linked to reduced eggshell quality, embryo mortality and reduced vitality.

Figure 1 – The presence of mycotoxins in poultry feed has been linked to a range of internal damage and production problems.

Threats to gut health in modern production

Poultry diets typically contain many different mycotoxins. While individual mycotoxins pose distinct concerns, one shared area of concern relates to how mycotoxins disrupt the intestinal barrier. The immune and epithelial cells in the intestinal tract are the first cells of contact for mycotoxins consumed in poultry feed. Even low mycotoxin concentrations can affect the intestinal epithelial cells which function as the essential barrier between the gut lumen and body tissue. As mycotoxins compromise the intestinal barrier, gut integrity is reduced and a more permeable gut wall allows access for more mycotoxins to invade.

Various mycotoxins are associated with gut health issues. Aflatoxins, Ochratoxins and T-2 toxin/DON have all been associated with disruptions in the intestinal barrier function. For example, Ochratoxins have been linked to increased permeability in the gut wall. Similarly, as T-2 toxin/DON compromises the tight junctions that seal the spaces between epithelial cells, openings can allow more mycotoxins to beabsorbed by the bird. When concentrations reach very high levels, T-2 toxin can even result in necrosis of the intestines and effect cytokine production. Fumonisin has also been linked to a reduction in tight junction proteins and an increase in intestinal permeability.

Table 1: Mycotoxin effect on gut health

Intestinal integrity and immunity are interrelated

Among livestock, poultry are unique in that a bird's gut and immune system are interrelated. About 70% of a bird's immune cells reside in the gut. Epithelial cells act as a protective and even lifesaving barrier just below the outer mucus layer, which is home to various commensals, pathogens, and antigens. Tight junctions lie between and seal the spaces between epithelial cells. When mycotoxins weaken or compromise the tight junctions, more mycotoxins can get into the blood stream setting off an inflammatory response and a cascade of adverse effects. These undesirable effects can include intestinal content leakage into submucosal tissues, which can trigger inflammation that affects intestinal morphology and nutrient transport. For example, DON exposure has been shown to reduce the villi height, reducing intestinal absorption, setting the stage for a modulatory effect that reduces the gut's detoxification capabilities and endotoxin liberation.

Another unwelcome consequence of a disrupted gut barrier is leakage of amino acids and proteins, which can lead to an electrolyte disbalance. Once tight junctions are compromised, not only can mycotoxins and pathogens get in, but a reverse transfer can occur where amino acids can leak out.

Figure 2 – Mycotoxins in feed can damage the intestinal wall causing a range of problems for gut health and immune system function.

Mycotoxins' effects on immunity can be seen in both the bird's innate immune system, which functions as a first line of defense, and in the adaptive immune system that vaccines seek to utilize. Various responses to exposure reflect the susceptibility of the immune system to various mycotoxins. The macrophagic phagocytosis – the basic mechanism required to mount all immune responses – has been shown to be suppressed when exposed to aflatoxins. Additionally, aflatoxin exposure has been linked to suppression of the delayed-type hypersensitivity (DTH) immune response and poor levels of antibody titers. Ochratoxins also have been linked to poor DTH. T-2 toxin has been linked to an increase in disease incidences, as has DON, along with poor antibody titers. Fumonisins have been linked to an increase in susceptibility to E. coli and other bacteria.

Table 2: Impact of mycotoxins on immune response

How do mycotoxins affect poultry's resilience to infectious agents?

Emerging toxins are becoming an increasing concern in many parts of the globe. Beyond compromising tight junctions, mycotoxins such as DON and fumonisins can adversely affect goblet cells which are important for producing mucus, can alter cytokine production and can even reduce the number of lymphocytes that can be produced by birds. All these negative effects reduce birds' resilience to infectious agents (Figure 3).

Figure 3. negative effects of emerging mycotoxins can reduce birds' resilience to infectious agents

Additionally, multiple mycotoxins have been linked to lowered antibody titers against Newcastle Disease (ND) and Infectious Bursal Disease (IBD). A practical example from India illustrates the reduction in antibody titers seen in birds fed 250 ppb each of Aflatoxin, OTA and T-2 for 42 days (a concentration level reasonably expected in many production environments). Compared to the control group, birds fed mycotoxins experienced a significant reduction in antibody titers.

Table 3: Multiple mycotoxins lowered antibody titer against NCD & IBD

Mitigating mycotoxin exposure while supporting gut health and immunity

While the bentonites used in mycotoxin binders can effectively bind aflatoxins, ergot toxins and bacterial/endotoxins, in the intestine, these interventions have moderate binding capabilities for T-2 toxin, Zearalenone and OTA – as well as very little binding to DON. An interesting finding regarding the use of binders is that fumonisins can be bound by bentonites at an acidic pH, but they get released back into the system at alkaline pH. Binders should function effectively at alkaline pH to mimic intestinal absorption patterns. With these findings in mind, it is clear that poultry producers need a strategy that goes beyond binding and considers other interventions that can support gut health and immunity. These insights are prompting additional research to understand how the role of immune modulators and gut health promoters can contribute to a multi-pronged approach to mycotoxin management. Mycotoxin risk management programmes should encompass every phase of the supply chain – from ingredients in the field through storage, transport, processing, and animal intake on the farm.

Interventions that support gut health and immunity, by reducing the bioavailability of mycotoxins to animals and remediating damage, are bringing broad-spectrum solutions to the poultry farm. An example of an intervention that supports gut wall protection can be seen in a study conducted by Trouw Nutrition in Canada and analyzed by the University of Guelph. A total of 1980 broilers were evaluated for 35 days in the presence of feed naturally contaminated with 6 ppm DON – high enough to be a challenge. Researchers saw a moderate decrease in the ratio of villi height to crypt depth at day 35 from DON which was significantly (p < 0.05) reversed by the addition of a binder.

Figure 4 – Adding binders and other mycotoxin mitigating feed additives to poultry diets helps reduce the negative side effects of mycotoxin contaminated feed. In another study, antibody titers against ND and IBD diseases in multiple mycotoxin-fed broiler chickens were significantly improved by the addition of binder at two different levels of inclusion (Figure 5).

Figure 5: Broilers fed mycotoxin-contaminated diets and receiving TOXO-XL had significant improvements in antibody titers against ND and IBD compared to a control group (p < 0.05).

The complexity of mycotoxins and their interactions with one another require a holistic approach to mycotoxin management. Research findings indicate that optimizing gut health and supporting birds' immunity can positively contribute to bird's ability to negate mycotoxin challenges and improve health and performance status, ultimately contributing to feed safety across the feed-to-food chain. As a Gold sponsor of the 2022 World Mycotoxin Forum, Trouw Nutrition will be presenting additional research during the 16-18 May 2022 event in Parma, Italy.

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Article made possible through the contribution of Trouw Nutrition

Trouw Nutrition Spotlights Mycotoxin Effects on Poultry Gut Health and Immunity in Advance of World Mycotoxin Forum Connects 2022