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Mycotoxins and their effects on gastro-intestinal tract

farming, africa, Mycotoxins, their, effects, gastro-intestinal, tractContamination of feed commodities by moulds and mycotoxins is considered to be one of the most important negative factors in crop production and animal feed quality

It is well documented that mycotoxin consumption causes a decrease in performance including decreased growth rate and poor feed efficiency (Pestka, 2007; Hanif et al., 2008). There has been extensive research addressing the different causes by which mycotoxins can alter animal productivity. In the current article, emphasis will be given to the effects of mycotoxins and endotoxins within the intestine that may contribute to an impaired health and immune status of the animals.

The gastrointestinal tract represents the first barrier against ingested chemicals, feed contaminants, and natural toxins. Following ingestion of mycotoxin-contaminated feed, intestinal epithelial cells can be exposed to high concentrations of toxins. Direct intestinal damage can be exerted by the biological action of mycotoxins. There are direct effects of trichothecenes on protein synthesis in eukaryotic cells. This is due to interaction with the ribosomal units preventing either initiation of protein synthesis or elongation of the polypeptidic chains (Ueno, 1984). Trichothecenes affect actively dividing cells such as those lining the gastrointestinal tract. Another relevant effect of some mycotoxins (fumonisin B1 and ochratoxin A) is that they alter the barrier function of the intestinal epithelium measured as a decrease in the transepithelial electrical resistance.

Poults fed grains naturally contaminated with Fusarium mycotoxins had decreased villus height in the duodenum, and decreased villus height and apparent villus surface in the jejunum, during the starter period. In addition to the morphological changes induced to the intestinal villi by DON it is suggested that this mycotoxin inhibits Na+ transport and Na+-D-glucose co-transport in the jejunum of layers resulting in a reduction of glucose uptake when the intestine is exposed to DON (Awad et al., 2005, 2007). Aflatoxins fed to broiler chickens decreased the production of pancreatic secretions whereas aflatoxins fed to layers produced an increase in the production of pancreatic enzymes (Osborne and Hamilton, 1981; Richardson and Hamilton, 1987).

Even though some bacterial strains are affected by mycotoxins there is evidence that mycotoxins increase pathogenic bacteria colonization of the intestinal tract in several animal species. Fumonisin B1 (0.5 mg/kg BW) challenge in pigs made them more susceptible to pathogenic E. coli colonization (Oswald et al., 2003). Similarly, layer chickens treated with ochratoxin A (3 mg/kg) had higher susceptibility to a Salmonella challenge compared to the control group (Fukata et al., 1996). E. coli challenge in broilers receiving an experimental diet containing 2 ppm of ochratoxin more than doubled the mortality compared to birds that received the bacterial challenge and a diet without mycotoxins. No birds died in the treatment receiving the diet with mycotoxin alone demonstrating that it is the combination of mycotoxins and pathogenic bacteria what causes the most devastating effects (Kumar et al., 2003).

Gross and histopathological lesions of birds inoculated with E. coli were also more severe in birds receiving a diet containing 2 ppm of ochratoxin than in birds receiving a diet with no significant levels of mycotoxins (Kumar et al., 2004). Parasitic infections are more severe in combination with mycotoxins. It has been demonstrated that birds treated with lasalocid do develop clinical coccidiosis when the levels of T-toxin exceeded 0.5 ppm (Varga and Ványi, 1992). Moreover, chronic ingestion of DON - comparable to concentrations occurring in contaminated food and feed - was reported to impair the intestinal transfer and uptake of nutrients.

Endotoxins and their effects on the gastro-intestinal tract

Endotoxins are lipopolysaccharides (LPS) derived from the cell membranes of Gram-negative bacteria and are responsible for its organization and stability. In pharmaceutical industries it is possible to find endotoxins during production processes or in the final product. Although endotoxins are linked within the bacterial cell wall, they are continuously liberated into the environment. The release does not happen only with cell death but also during growth and division. A single Escherichia coli contains about 2 million LPS molecules per cell.

Since bacteria can grow in nutrient poor media, such as water, saline, and buffers, endotoxins are found almost everywhere. Endotoxins are present in dust, feed, drinking water as a part of a bacterial cell wall or as fragments of whole bacteria. The mucosal surface of the gastrointestinal tract (GIT) is covered with a one cell layer, the mucosal epithelium. Intestinal epithelium is constantly exposed to gram negative bacteria, which are able to directly deposit their toxic and proinflammatory constituents such as LPS at the intestinal epithelial apical surface. LPS is a potent toxin that elicits several immediate proinflammatory responses in mammalian cells.

Despite the density of these bacteria and their toxins, the intestinal epithelium does not activate proinflammatory responses to these organisms. Both innate and acquired immune systems protect the GIT against microbial endotoxins. In conditions where the body is exposed to LPS excessively or systemically (as when small concentrations of LPS enter the blood stream), a systemic inflammatory reaction can occur, leading to multiple pathophysiological effects, such as endotoxin shock, tissue injury, and death (Anspach, 2001; Erridge et al., 2002; Ogikubo et al., 2004). However, endotoxin does not act directly against cells or organs but through activation of the immune system, especially through monocytes and macrophages, with the release of a range of proinflammatory mediators, such as tumor necrosis factor (TNF), interleukin (IL)-6 and IL-1 (Magalhaes et al., 2007).

Although ultimately beneficial in treating the infection, antibiotic therapy has been hypothesized to initially increase the circulating load of free endotoxin by killing or lysing the infecting bacteria (Shenep et al., 1984, 1985, 1988; Simmons and Stolley, 1974).

Antimicrobials have been used for more than 50 years to enhance growth performance and to prevent disease in livestock feeding environments (Gustafson and Bowen, 1997). There is growing concern about the potential of antimicrobials in livestock diets to contribute to the growing list of antibiotic-resistant human pathogens (Corpet, 1996;  Williams and Heymann, 1998). Although the use of antimicrobials for growth promotion in livestock diets is still allowed in the United States, most countries in Europe are implementing strict guidelines and regulations for the use of dietary antimicrobials (Regulation (EC), 2003). In the event that restrictions are placed upon the use of antimicrobials in commercial swine feeding operations, many animal scientists have begun to investigate natural alternatives to conventional chemotherapeutic agents.

Several drugs have been investigated to counteract endotoxins.  Antibiotics differ in potential for endotoxin liberation according to their bacteriostatic or bactericidal effect. Antibiotics can also bind endotoxins, Polymyxin B or Colistin being the example, but were shown to be toxic themselves. The most remarkable adverse effects of these drugs are nephrotoxicity (chiefly acute renal failure) and neurotoxicity (Mendes and Burdmann, 2010).

The use of antibiotics in farming operations (therapeutic use) clearly leads to the development of antibiotic-resistant pathogens. This causes problems when those antibiotic-resistant pathogens get into people. That is why a feed additive was developed for its positive effect on health and immune status of animals exposed to mycotoxins and endotoxins.

Bioactive components and their action

The Mycofix® product line offers a complex-strategy solution for the counteraction of mycotoxin and endotoxin effects. Adsorption components enable the binding of both, adsorbable mycotoxins (aflatoxins, fumonisins, ergot alkaloids) and endotoxins. The biological constituent and inactivated bioprotein biotransform non-adsorbable mycotoxins into non-toxic metabolites. On one hand the biological constituent stimulates the production of the anti-inflammatory cytokine (IL-10) and the macrophage activity and on the other hand it inhibits the production of pro-inflammatory cytokines (IL-6 and TNF-α). Moreover, the phytophytic substance incorporated in the Mycofix® product line in order to protect the liver seems to be very effective in inhibiting pro-inflammatory cytokines (IL-6 and TNF-α) production. The phytogenic substances inhibit pro-inflammatory cytokine (IL-6) production therefore support the immune system.