Most
grains used as feed raw materials are susceptible to mycotoxin contamination.
These toxic secondary metabolites are produced by fungi before or after harvest
and cause severe economic losses all along agricultural value chains. For
livestock, negative consequences include acute effects such as impaired liver
and kidney function, vomiting, or anorexia, as well as chronic effects such as
immunosuppression, growth retardation, and reproductive problems. Mycotoxin
management is, therefore, of the utmost priority for animal producers
worldwide.
But
how is it that mycotoxins cause such damage in the first place? This article
delves into the complex processes that take place when mycotoxins come into
contact with the gastrointestinal tract (GIT). The intestinal epithelium is the
first tissue to be exposed to mycotoxins, and often at higher concentrations
than other tissues. A deeper understanding of how mycotoxins affect the GIT
allows us to appreciate the cascading effects on animal health and performance,
why such damage already occurs at contamination levels well below official
safety thresholds – and what we can do about it.
THE
INTESTINAL EPITHELIUM: THE BUSY TRIAGE SITE FOR NUTRIENTS AND HARMFUL
SUBSTANCES
When
mycotoxins are ingested, they encounter the GIT’s intestinal epithelium (Figure
1). This single layer of cells lining the intestinal lumen serves two
conflicting functions: firstly, it must be permeable enough to allow the
absorption of nutrients. On the other hand, it constitutes the primary
physiological barrier against harmful agents such as viruses, microorganisms,
and toxins.
Within
the intestinal epithelium, several types of highly specialized cells are
involved in epithelial regeneration, nutrient absorption, innate defense,
transport of immunoglobulins, and immune surveillance. The selective barrier
function is maintained due to the formation of complex networks of proteins
that link adjacent cells and seal the inter-cellular space. Besides, the
intestinal epithelium is covered with mucus produced by goblet cells, which
isolates its surface, preventing the adhesion of pathogens to the enterocytes
(intestinal absorptive cells).
Due
to its dual involvement in digestive and immune processes, the intestinal
epithelium plays a pivotal role in the animal’s overall health. Importantly,
the epithelium is directly exposed to the entire load of ingested mycotoxins.
Hence their effects can be problematic even at low concentrations.
Figure 1: The intestinal epithelium
PROBLEMATIC
EFFECTS OF MYCOTOXINS ON THE INTESTINAL EPITHELIUM
Most
mycotoxins are absorbed in the proximal part of the gastrointestinal tract
(Table 1). This absorption can be high, as in the case of aflatoxins (~90%),
but also very limited, as in the case of fumonisins (<1%); moreover, it
depends on the species. Importantly, a significant portion of unabsorbed toxins
remains within the lumen of the gastrointestinal tract.
Some
of the mycotoxins that enter the intestinal lumen can be bio-transformed into less toxic compounds by
the action of certain bacteria. This action, however, predominantly happens in
the large intestine – therefore, no detoxification takes place before
absorption in the upper parts of the GIT. Part of the absorbed mycotoxins can
also re-enter the intestine, reaching the cells from the basolateral side via
the bloodstream. Furthermore, they re-enter through enterohepatic circulation (the
circulation of substances between the liver and small intestine). Both actions
increase the gastrointestinal tract’s overall exposure to the toxins.
Table 1: Rate and absorption sites of different mycotoxins
The damaging impact of mycotoxins on
the intestinal epithelium initially occurs through:
- A decrease in protein synthesis, which reduces barrier
and immune function (Van de Walle et al., 2010)
- Increased oxidative stress at the cellular level, which
leads to lipid peroxidation, affecting cell membranes (Da Silva et al., 2018)
- Changes in gene expression and the production of
chemical messengers (cytokines), with effects on the immune system and
cellular growth and differentiation (Ghareeb et al., 2015)
- The induction of programmed cell death (apoptosis),
affecting the reposition of immune and absorptive cells (Obremski & Poniatowska-Broniek, 2015)
Importantly,
studies based on realistic mycotoxin challenges (e.g., Burel et al., 2013) show that the mycotoxin
levels necessary to trigger these processes are lower than the levels reported as safe by
EFSA, the Food Safety Agency of the European Union. The ultimate consequences
range from diminished nutrient absorption to inflammatory responses and
pathogenic disorders in the animal (Figure 2).
Figure 2: Mycotoxins’ impact on the GIT and consequences for monogastric animals
1. Alteration of the intestinal barrier‘s morphology and
functionality
The
mycotoxins DON, fumonisin, and T2 induce a reduction in the rate of epithelial cell proliferation and
differentiation. This causes a decrease in the height and the
surface of the intestinal villi, which in turn leads to a reduction in nutrient
absorption. Additionally, some nutrient transporters are inhibited by
the action of mycotoxins such as DON and T2, for example, negatively affecting
the transport of glucose.
Several
studies indicate that mycotoxins such as aflatoxin B1, DON, fumonisin B1,
ochratoxin A, and T2, can increase the permeability of the intestinal
epithelium of poultry and swine (e.g. Pinton & Oswald, 2014). This is mostly a
consequence of the inhibition of protein synthesis. As a result, there is an
increase in the passage of antigens into the bloodstream (e.g., bacteria,
viruses, and toxins). This increases the animal’s susceptibility to infectious
enteric diseases. Moreover, the damage that mycotoxins cause to the intestinal
barrier entails that they are also being absorbed at a higher rate.
2. Impaired immune function in the intestine
The
intestine is a very active immune site, where several immuno-regulatory
mechanisms simultaneously defend the body from harmful agents. Immune cells are affected by mycotoxins through
the initiation of apoptosis, the inhibition or stimulation of cytokines, and
the induction of oxidative stress. Studies demonstrate that aflatoxin, DON,
fumonisin, T2, and zearalenone interact with the intestinal immune system in
such a manner that the animal’s susceptibility to viral and bacterial
infections increases (e.g., Burel et al., 2013).
Moreover, by increasing their fecal elimination, the horizontal transmission of
pathogens is extended.
For
poultry production, one of the most severe enteric problems of bacterial origin
is necrotic enteritis, which is caused by Clostridium
perfringens toxins. Any agent capable of disrupting the
gastrointestinal epithelium – e.g. mycotoxins such as DON, T2, and ochratoxin –
promotes the development of necrotic enteritis. The
inhibition of the intestinal immune system caused by mycotoxins such as
aflatoxin, DON, and T2 also collaborates with the development of this disease.
3. Alteration of the intestinal microflora
The
gastrointestinal tract is home to a diverse community of bacteria, fungi,
protozoa, and viruses, which lines the walls of the distal part of the
intestine. This microbiota prevents the growth of pathogenic bacteria through
competitive exclusion and the secretion of natural antimicrobial compounds,
volatile fatty acids, and organic acids.
Recent
studies on the effect of various mycotoxins on the intestinal microbiota show
that DON and other trichothecenes favor
the colonization of coliform bacteria in pigs. DON and
ochratoxin A also induce a greater invasion of Salmonella and
their translocation to the bloodstream and vital organs in birds and pigs –
even at non-cytotoxic concentrations. It is known that fumonisin B1 may induce
changes in the balance of sphingolipids at the cellular level, including for
gastrointestinal cells. This facilitates the adhesion of pathogenic bacteria,
increases in their populations, and prolongs infections, as has been shown for the case of E. coli.
From
the perspective of human health, the colonization of the intestine of food-producing
animals by pathogenic strains of E. coli and Salmonella is
of particular concern. Mycotoxin exposure may well increase the transmission of
these pathogens, posing a risk for human health.
4.
INTERACTION WITH BACTERIAL TOXINS
When
mycotoxins induce changes in the intestinal microbiota, this can lead to an
increase in the endotoxin concentration in the intestinal lumen. Endotoxins or
lipopolysaccharides (LPS) are fragments of Gram-negative bacteria’s cell walls.
They are released during bacterial cell death, growth, and division. Hence
endotoxins are always present in the intestine, even in healthy animals. Endotoxins promote the release of several cytokines that
induce an enhanced immune response, causing inflammation, thus reducing feed
consumption and animal performance, damage to vital organs, sepsis, and death
of the animals in some cases.
The
synergy between mycotoxins and endotoxins can result in an overstimulation of
the immune system. The interaction between endotoxins and estrogenic agents
such as zearalenone, for example, generates chronic inflammation and autoimmune disorders because
immune cells have estrogen receptors, which are stimulated by the mycotoxin.
The combination of DON at low concentrations and endotoxins in the intestine,
on the other hand, has been shown to engender a decrease in transepithelial resistance and
to alter the balance of the microbiota.
What to do? Proactive toxin risk
management
To
prevent the detrimental consequences of mycotoxins on animal health and
performance, proactive solutions are needed that support the intestinal
epithelium’s digestive and immune functionality and help maintain a balanced
microbiome in the GIT. Moreover, it is crucial for any anti-mycotoxin product
to feature both anti-mycotoxin and anti-bacterial toxin properties and that it
supports the organs most targeted by mycotoxins, e.g., the liver. EW
Nutrition’s Mastersorb® Gold premix is based on the synergistic combination of
natural clay minerals, yeast cell walls, and phytomolecules. Its efficacy has
been extensively tested, including as a means for dealing with E. coli endotoxins.
Mastersorb® Gold: anti-mycotoxin activity stabilizes performance
and strengthens liver health
A
field trial conducted in Germany on male Ross 308 broilers showed that for
broilers receiving a diet contaminated with DON and zearalenone, adding 1kg of
Mastersorb® Gold per ton of feed to their diet led to significant performance
enhancements. Not only did they recuperate the mycotoxin-induced weight loss
(6% increase relative to the group receiving only the challenge), but they
gained weight relative to the control group (which received neither the
challenge nor Mastersorb® Gold). Feed conversion also improved by 3% relative
to the group challenged with mycotoxins.
A
scientific study of crossbred monogastric showed that Mastersorb® Gold
significantly reduced the deleterious effects of fumonisin contamination in the
feed. The decrease in weight gain and the decline of feed conversion could be
mitigated by 6.7% and 13 FCR points, respectively (Figure 3). Also, the
sphinganine/sphingosine (Sa/So) ratio, a biomarker for fumonisin presence in
the blood serum, could be decreased by 22.5%.
Figure 3: Mastersorb® Gold boosts performance for monogastric fed a fumonisin-contaminated diet
Another
study of crossbred female piglets, carried out at a German university,
investigated whether Mastersorb® Gold could support performance as well as
liver health under a naturally occurring challenge of ZEA (~ 370ppb) and DON (~
5000ppb). Mastersorb® Gold significantly improved weight gain and feed
conversion in piglets receiving the mycotoxin-contaminated diet: daily body
weight gain was 75g higher than that of a group receiving only the challenge,
and the FCR improved by 24% (1.7 vs. 2.25 for the group without Mastersorb®
Gold). Moreover, Mastersorb® Gold significantly improved the liver weight
(total and relative) and the piglets’ AST levels (aspartate aminotransferase,
an enzyme indicating liver damage). A tendency to improve spleen weight and GGT
levels (gamma-glutamyl transferase, another enzyme indicative of liver issues)
was also evident, all of which indicate that Mastersorb® Gold effectively
counteracts the harmful impact of mycotoxin contamination on liver
functionality.
In-vitro studies demonstrate Mastersorb® Gold’s effectiveness
against mycotoxins as well as bacterial toxins
Animal
feed is often contaminated with two or more mycotoxins, making it important for
an anti-mycotoxin agent to be effective against a wide range of different
mycotoxins. Besides, to prevent mycotoxins damaging the GIT, an effective
product should ideally adsorb most mycotoxins in the first part of the animal’s
intestine (under acidic conditions). In-vitro experiments at an independent
research facility in Brazil showed that an application of 0.2% Mastersorb® Gold
binds all tested mycotoxins at rates from 95 to 97% at a pH level of 3, using
realistic challenges of 1000ppb (Aflatoxin B1 and ZEA) and 2500ppb (Fumonisin
B1 and DON). The binding results achieved for Fumonisin and DON, which are
often considered outright “nonbinding,” under challenging close to neutral
conditions (pH 6), are particularly encouraging.
Figure 4: Mastersorb® Gold binding capacity against different mycotoxins (%)
Concerning
its efficacy against endotoxins, an in vitro study conducted
at Utrecht University, among other studies, has shown Mastersorb® Gold to be a
strong tool against the LPS released by E. coli. For the test,
four premium mycotoxin binders were suspended in a phosphate buffer solution to
concentrations of 0.25% and 1%. E. coli LPS were suspended to
a final concentration in each sample of 50ng/ml. Against this particularly high
challenge, Mastersorb® Gold achieved a binding rate of 75% at an inclusion rate
of 1%: clearly outperforming competing products, which at best showed a binding
rate of 10%.
CONCLUSION
A
healthy gastrointestinal tract is crucial to animals’ overall health: it
ensures that nutrients are optimally absorbed, it provides effective protection
against pathogens through its immune function, and it is key to maintaining a
well-balanced microflora. Even at levels considered safe by the European Union,
mycotoxins can compromise different intestinal functions such as absorption,
permeability, immunity, and microbiota balance, resulting in lower productivity
and susceptibility to disease.
To
safeguard animal performance, it is important to continually strive for low
levels of contamination in feed raw materials – and to stop the
unavoidable mycotoxin loads from damaging the intestinal epithelium through the
use of an effective anti-mycotoxin agent, which also supports animals against
endotoxins and boosts liver function. Research shows that Mastersorb® Gold is a
powerful tool for proactive producers seeking stronger animal health, welfare,
and productivity.
By Marisabel Caballero and Sabria
Regragui Mazili
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