Deoxynivalenol (DON, vomitoxin) is the most common trichothecene Fusarium mycotoxin detected globally in contaminated raw materials and feeds. A recent (2019) Trouw Nutrition Global Mycotoxin Survey (Figure 1) has proved the same, wherein more than 90% of the samples tested contained quantifiable amounts of DON. The term "DON-contaminated grains" has been used in the research where naturally-contaminated grains are used as source of DON. In reality, such grains can contain several other mycotoxins such as 3-acetyl DON, 15-acetyl DON, fusarenone-X, nivalenol, fusaric acid (FA) etc in addition to DON. This is the reason why the presence of DON in raw materials is used as a marker for the presence of several other mycotoxins. In recent times, masked mycotoxin DON-3-glucoside (DON-3G) is also detected in grains contaminated with DON and in some cases, its presence can tune up to 100% of DON. Such presence of multiple mycotoxins has led to mycotoxin additive and synergistic interactions leading to unexpected toxicities in livestock and poultry.

Chronic DON mycotoxicoses in animals are characterized by loss of appetite, reduced weight gains, increased FCR, altered serum chemistry and organ weights, compromised intestinal health and increased susceptibility to diseases. At DON concentrations of more than 6ppm in feed, there are reports of vomition in pigs as well and hence, the name vomitoxin. Pigs are considered to be more susceptible to DON toxicity than poultry (Trenholm et al., 1984). Such species susceptibility differences led to EFSA's DON guidance values of 5ppm for poultry but 0.9ppm for pigs. The objective of this article is to provide some scientific basis for differential effects of DON in poultry and swine.

The role of neurotransmitters in DON toxicity

Three types of neurotransmitters, namely serotonergic, dopaminergic and noradrenergic, are thought to be involved in the feed intake reduction effect of DON. Tryptophan (TRP), 5-hydroxytryptamine (5HT, serotonin), and 5-hydroxyindoleacetic acid (5HIAA) are the main serotonergic neurotransmitters while dopamine (DA), dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and homovanillic acid (HVA) are some of mainly studied dopaminergic and noradrenergic neurotransmitters. In the previous studies, purified DON and FA have been shown to sequentially elevate brain serotonergic neurotransmitter concentrations in pigs and this has been linked to a decrease in feed intake. No such information was available in broiler chickens. The feeding of T-2 toxin, another of the trichothecene mycotoxins, however, increased dopamine (DA) and decreased norepinephrine (NE) concentrations in brains of broiler chickens, but 5HT concentrations were unaltered (Chi et al., 1981).

Based on some of the available information, we hypothesized that the differences in alterations of brain neurochemistry in broiler chickens and starter pigs might be one of the possible mechanisms for species differences in the severity of DON-induced feed refusal (Swamy et al., (2004). To prove this, two experiments were conducted to determine the effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins (predominantly DON) on regional brain neurochemistry of starter pigs and broiler chickens. Such comparison would aid in making the correct decision on the possible diversion of DON-contaminated grains from swine to poultry.

Effects on performance parameters

In the study of Swamy et al. (2004), pigs were fed approximately half the amount of contaminated grains that was fed to broiler chickens (pigs – 5.5ppm; chickens – 9.7ppm). The feed intake and weight gains in starter pigs was reduced by 32 and 34%, respectively, while the decrease in broiler chickens were 15% and 12%. The reduced performance parameters in pigs were consistent, while those in chickens were variable. It was concluded that starter pigs are more susceptible to the feeding of DON-contaminated grains than broiler chickens with respect to growth parameters. The next heading talks about the reason for such differential effects of DON on performance of these two species of animals.

Effects on serotonergic neurotransmitters

In the study of Swamy et al. (2004), mycotoxin-induced increases in the concentrations of serotonergic neurotrasmitters were common to both species, while changes in the concentrations of noradrenergic and dopaminergic neurotransmitters varied (Table 1). Feeding of DON-contaminated grains increased 5-HT/5-HIAA ratio in pigs while absolute concentrations of 5-HT and 5-HIAA increased in broiler chickens. Such a stimulatory effect on serotonergic activity is known to reduce feed intake. The study showed decreased DA, DOPAC, HVA, and NE concentrations in the pigs fed contaminated diets but the opposite effects were observed in broiler chickens.

The medial hypothalamus of the brain is richly populated both with serotonergic and α2-noradrenergic receptors. The stimulation of these receptors with the neurotransmitters has important implications on feeding behavior. There is strong evidence that serotonergic and α2-noradrenergic systems interact antagonistically through medial hypothalamic satiety mechanisms. The lack of an antagonistic interaction of these two systems on feed intake might explain feed refusal in pigs. In contrast, both NE and serotonergic neurotransmitter concentrations were increased in broiler chickens, thus permitting the possible antagonistic interaction between two systems. This situation might explain the less severe feed refusal seen in broiler chickens.

A recent proof that poultry is less sensitive to DON

Metayer et al. (2019) designed an experiment in broiler chickens to study the interaction of DON with fumonisins (FB) and zearalenone (ZON) at the concentrations equivalent to EFSA guidance values. Experimental corn-soybean diets incorporated ground cultured toxigenic Fusarium strains. The control diets were mycotoxin free, the DON diets contained 5 ppm DON, the FB diet contained 20ppm FB and the ZON diet contained 0.5ppm ZON. The DON-FB-ZON diet contained 5, 20, and 0.5ppm DON, FB and ZON, respectively. No difference between groups that could be attributed to these mycotoxins was observed in performances, the relative weight of organs, biochemistry, histopathology, intestinal morphometry, variables of oxidative damage, and markers of testicle toxicity. Taken together, these results suggest that the regulatory guidelines established for single contamination of broiler chickens fed with DON, FB, and ZON can also be used in the case of multiple contamination with these toxins. This also confirms that poultry can tolerate DON much better than pigs. However, it is suggested to study immune parameters in depth in poultry exposed to DON-contaminated grains.

Implications

· Altered brain regional neurochemistry in pigs and broiler chickens chronically fed DON-contaminated diets provided a mechanistic basis for the negative effect of DON on feed intake.

· The pattern of brain neurotransmitter alterations, however, differed between the two species, which might explain species differences in the severity of reduced feed intake and the subsequent growth depression. These findings suggest that caution should be exercised in diverting DON-contaminated grains from swine to poultry feed.

· Due to the upfront reduction in feed intake in pigs exposed to DON-contaminated grains, immune parameters may not be exposed much to DON. However, in case of chickens, DON exposure to immune organs will be much higher owing to its lower impact on feed intake. Immune parameters in poultry exposed to DON-contaminated grains must be studied further in detail.

Table 1. Effects of DON on various neurotransmitters in brain

For more of the article, please click here.

Article made possible through the contribution of Swamy Haladi, PhD and Trouw Nutrition Netherlands

Differential effects of DON in swine and poultry