Mycotoxins alter the intestinal barrier and promote the passage of endotoxins into the bloodstream

What are endotoxins?

Endotoxins are bacterial toxins (from the Greek, endo = interior; toxin = poison). They constitute the main component of Gram-negative bacterial cell wall, such as Salmonella spp. and Escherichia coli. They are found in the intestinal tract of healthy animals covering 75% of the bacterial cell surface and are continuously released into the intestinal lumen after the lysis or proliferation of the bacteria (Reisinger et al., 2016).

Endotoxins are also known as “Lipopolysaccharides” (LPS) due to their structure: lipids and sugars. Specifically, LPS are chemically composed of a lipid (Lipid A), the coreand an external chain of polysaccharides (O-Antigen).

Las endotoxinas también son conocidas como “Lipopolisacáridos” (LPS) de acuerdo con su estructura: lípidos y azúcares. En concreto, los LPS están compuestos químicamente por un lípido (Lípido A), el núcleo y una cadena externa de polisacáridos (antígeno O).

Lipid A is attached to the bacteria and is the most conserved and bioactive fraction ofthe endotoxin. On the other hand, O-Antigen differs between bacterial serotypes (Sarmikasoglou and Faciola, 2021).

When do endotoxins pose a risk to animal health?

Unlike other bacterial toxins, the toxic effects of endotoxins are observed only when released from the bacterial wall. In fact, under homeostasis conditions, endotoxins are found in the intestinal tract and pose no risk to animal health. However, when the integrity of the intestinal barrier is compromised, endotoxins can translocate into the bloodstream. The immune system can manage low endotoxin levels in the blood. Nevertheless, constant amounts of endotoxin may overload the detoxification metabolism of the organism and change livestock’s physiology (Erlanson-Albertssonand Stenkula, 2021).

Additionally, different factors can critically promote the presence of endotoxins, cause the liberation of endotoxins and/or favor their passage into bloodstream:

Infections caused by Gram-negative bacteria inherently increase the amount of endotoxins in the organism.
Diets rich in nutrients that promote bacterial growth in the intestinal tract.
Use of bactericides that induce the release of endotoxins.
High-fat diets, especially saturated fatty acids, facilitate the translocation of endotoxins to the bloodstream by sharing the adsorption process.
Infectious and non-infectious challenges such as mycotoxins or periods of high production, weaning etc. that compromise the intestinal integrity, increasing its permeability and favoring the passage of the endotoxins to the bloodstream.
Challenges that cause hepatic injury and limit the metabolism and excretion of the endotoxins.  

In those scenarios, the presence of endotoxins in plasma (endotoxemia) induces a potent inflammatory response that could ultimately compromise the performance parameters of livestock. In addition, it can also produce multi-organ failure and death. Furthermore, endotoxins are aggravating factors in some diseases and the clinical profile may vary according to the animal species (Zhang et al., 2016; Reisinger et al., 2020).

Mycotoxins open the curtains on the endotoxin show

Mycotoxins compromise the intestinal integrity by deteriorating the epithelial morphometry, the most interior part of the mucous membrane which is vital for the intestinal barrier function. It’s well known that oxidative stress and DNA damage induced by mycotoxins, such as DON, induce apoptosis. In this context, a reduction in the villi height and the depth of the crypt is observed, which can compromise the absorption of nutrients, a possible source of energy for enteropathogens. Furthermore, mycotoxins can cause changes in the mucin’s composition, promoting the presence of endotoxins in the lumen. In addition, mycotoxins alter the expression of tight junctions and pro-inflammatory factors, increasing intestinal permeability andfacilitating the passage of endotoxins from the intestine into the bloodstream and the spread to internal organs (Ren et al., 2019). Recently, it’s been demonstrated that the co-exposition of mycotoxins and endotoxins increases the negative effect in intestinal permeability. In fact, Ruhnau et al. (2020) observed a higher translocation of endotoxins from E. coli to the liver and spleen in chickens simultaneously exposed to DON and the bacterium.

On the other hand, exposure to mycotoxins can provide favorable conditions for the growth of some enterobacteria, such as Campylobacter, and disrupt the homeostasis of the gut microbiota, leading to the liberation of endotoxins.

How to mitigate the impact of endotoxins, a side-effect of mycotoxin exposition?

In this scenario, the specific combination of minerals, phytogenic and organic compounds from BIŌNTE® QUIMITŌX® PLUS, allows to bind toxins, promote the intestinal integrity, and mitigate the oxidative stress and hepatic damage tocounteract the synergistic effects of mycotoxins and endotoxins.

On the front line of the battle against endotoxins, the postbiotic effect of BIŌNTE® QUIMITŌX® PLUS, attributed to the selected yeast, stands out. On the one hand, the included yeast cell wall highlights for its β-glucans with high adsorbent capacity for mycotoxins, as well as for its immunostimulating effect. On the other hand, hydrolyzed yeast present in the formula provides interesting mannan-oligosaccharides to agglutinate endotoxins, favors the nutrients assimilation and is a source of vitamins and nucleotides that can promote the improvement of performance parameters. Moreover, the combination of selected yeasts has a modulating factor of gut microbiota that, at the same time, inhibits the presence of endotoxins.

In vitro assay to evaluate the efficacy of BIŌNTE® QUIMITŌX® PLUS against endotoxins

In order to evaluate the binding capacity of BIŌNTE® QUIMITŌX® PLUS against the endotoxins of Salmonella spp. and E. coli, an in vitro study was carried out in collaboration with Molendotech Ltd. (United Kingdom), a well-known laboratory in the study of endotoxins

BIŌNTE® QUIMITŌX® PLUS binds 73% of the endotoxins of Salmonella spp. and 24% of E. coli endotoxins.

The results of the study demonstrated that BIŌNTE® QUIMITŌX® PLUS adsorbs both mycotoxins and endotoxins simultaneously, effectively preventing their synergistic effects that could compromise animal health.

In conclusion, this study revealed the adsorption capacity of BIŌNTE® QUIMITŌX® PLUS not only to mitigate the effect of the mycotoxins, but also of the endotoxins. Specifically, it was obtained a 73% adsorption of Salmonella Typhimurium and 24% of Escherichia coli.

This effect was achieved thanks to the combination of ingredients of the anti-mycotoxins product BIŌNTE® QUIMITŌX® PLUS which includes adsorbent material, phytogenics and, notably, the selected yeast that contributes to the postbiotic effect, thereby protecting the animal health.

The study presented in this article was conducted in collaboration with MolendotechLtd.