The Link between Endotoxins and Mycotoxins

The Link between Endotoxins and Mycotoxins

Toxins from within

One of the problems with endotoxins is that they can be produced in the rumen. Not all types of bacteria produce endotoxins, only Gram-negative bacteria. The term Gram-negative is based on reaction to a Gram stain under the microscope. Gram-negative bacteria do not retain the stain, mainly because the structure of their cell wall includes lipopolysaccharides (LPS or endotoxins) on the outer membrane. When Gram-negative bacteria die, the endotoxins are released. During fast growth of Gram negative bacteria, there can also be significant “shedding” of endotoxins.

Endotoxins are always present in the rumen to some extent, but at higher levels, they can compromise the integrity of the gut wall and impact animal health. Endotoxin production is one potential consequence of acidosis because as higher levels of grains are fed, there is a general shift from Gram-positive to Gram-negative bacteria. Figure 1 shows how the level of endotoxins increases significantly if the rumen remains at a pH below 6 for a prolonged period of time. Subacute ruminal acidosis (SARA) challenge is often described as the rumen pH being below 5.8 for more than five hours per day, thus SARA also represents an endotoxin risk.

Endotoxins may affect the tight junctions or cause apoptosis of epithelial cells, increasing the uptake of undesirable substances into the blood stream. Endotoxins themselves are also able to enter the bloodstream and research suggests a link between endotoxins and laminitis (Figure 2) and other health issues. One of the key impacts of endotoxins is an inflammatory response, which represents a waste of energy for the animal as well as cell damage leading to health issues. Figure 2 shows how the Biomin® Bioprotection Mix in Mycofix® can reduce some of this damage.

Figure 1. SARA and endotoxins. Increasing endotoxin concentrations (in EU endotoxin units/mL) found in rumens that had longer duration per day of pH below 6. Note: the endotoxin axis is on a log scale so at 5 the endotoxin concentration is ten times as high as at 4.

Figure 1. SARA and endotoxins. Increasing endotoxin concentrations (in EU endotoxin units/mL) found in rumens that had longer duration per day of pH below 6. Note: the endotoxin axis is on a log scale so at 5 the endotoxin concentration is ten times as high as at 4.

Figure 2. The link between endotoxins and laminitis in cattle and horses. Endotoxins (LPS) in an “ex vivo, in vitro” experiment reduced the force required to separate layers of the hoof (indicative of laminitis). The asterisk indicates a statistically significant effect (P < 0.05). The hoof material was unaffected when the Biomin® Bioprotection Mix was added.

Figure 2. The link between endotoxins and laminitis in cattle and horses. Endotoxins (LPS) in an “ex vivo, in vitro” experiment reduced the force required to separate layers of the hoof (indicative of laminitis). The asterisk indicates a statistically significant effect (P &lt; 0.05). The hoof material was unaffected when the Biomin® Bioprotection Mix was added. 

The response to endotoxins can also reduce the appropriate immune response, thus increasing disease susceptibility. The high osmolarity due to soluble carbohydrate levels associated with SARA may increase the amount of endotoxins crossing into the bloodstream. High osmolarity leads to increased water flow out of the bloodstream, resulting in some dislodging and eventually the death of epithelial cells, allowing increased uptake of endotoxins and other undesirable substances, such as mycotoxins.

Mycotoxins and Endotoxins

can also have an impact on the intestinal barrier function and so increase the risk of endotoxin uptake into the bloodstream. Similarly, the negative effect of endotoxins on the rumen epithelium may increase the uptake of mycotoxins, increasing the risk to the animal of even hard-to-absorb mycotoxins such as fumonisins. Both mycotoxins and endotoxins can trigger inflammatory and immunosuppressive effects (through reducing response or directly affecting immune cells) and both toxin types can affect, and be exacerbated by, liver damage.

The Effect of Heat

There is a strong link between heat stress and endotoxins. Heat stress increases blood flow to the skin at the expense of the rumen. This deprives epithelial cells of necessary oxygen and allows toxic substances to accumulate. Endotoxin uptake can increase through these damaged cells. Heat stress can also increase the impact of mycotoxins. In addition, both mycotoxins and endotoxins can increase and prolong the negative effects of heat stress.

Management of Endotoxins and Mycotoxins

Management should include steps to reduce heat stress and to balance the diet according to the different demands of productivity and rumen condition. Mycofix® Plus has three strategies to help overcome the combined effects of endotoxins and mycotoxins. An effective binding component can adsorb endotoxins and mycotoxins simultaneously with high efficacy (Figure 3).

Figure 3. Simultaneous binding of aflatoxin and endotoxins. Left hand side: In vitro adsorption efficacy of Mycofix® Plus (0.02%) on aflatoxins (4000ppb) remains the same in the presence of a high level of endotoxin (500 EU/mL). Right hand side: In vitro absorption efficacy of Mycofix® Plus (0.02%) on endotoxin (LPS) binding was similar in the presence or absence of aflatoxins.

Figure 3. Simultaneous binding of aflatoxin and endotoxins. Left hand side: In vitro adsorption efficacy of Mycofix® Plus (0.02%) on aflatoxins (4000ppb) remains the same in the presence of a high level of endotoxin (500 EU/mL). Right hand side: In vitro absorption efficacy of Mycofix® Plus (0.02%) on endotoxin (LPS) binding was similar in the presence or absence of aflatoxins.

In addition to adsorption, a unique and effective biotransformation approach for the difficult-to-bind mycotoxins such as trichothecenes is important to address the direct effects in the animal and their indirect intensifying of endotoxin damage. The third strategy of Mycofix® Plus is to provide protection for the vulnerable epithelial cells, liver cells and immune cells with research-proven bioprotection derived from phytogenic and algal ingredients.

In Brief
  • Endotoxins can be produced in the rumen by Gramnegative bacteria. Mycotoxins are ingested through contaminated feed ingredients.
  • At higher levels, endotoxins can compromise the integrity of the gut wall, allowing more undesirable substances, including endotoxins and mycotoxins, to pass into the bloodstream, impacting animal health.
  • The presence of mycotoxins can increase the uptake of endotoxins and the presence of endotoxins can increase the uptake of mycotoxins.
  • The multicomponent strategy of Mycofix® can help overcome the combined effects of endotoxins and mycotoxins.

References

Reisinger, N., Schaumberger, S. and Schatzmayr, G. (2017). Einfluss von Endotoxinen auf das Klauengewebe in einem ex vivo Modell. 55th BAT Tagung. 12.10.2017. Freising, Germany.

Zebeli, Q., Metzler-Zebeli, B.U. and Ametaj, B.N. (2012). Meta-analysis reveals threshold level of rapidly fermentable dietary concentrate that triggers systemic inflammation in cattle. Journal of Dairy Science. 95(5). pp. 2662-2672.

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