Mycotoxin and Gut Microbiota Interactions

Mycotoxins are secondary metabolites produced by fungi, the most abundant of which belong to the genera Aspergillus, Penicillium, and Fusarium. The conditions required for fungal development and the production of mycotoxins vary strongly with the substrate on which the fungal species develop.Because mycotoxins are mainly present in food and feed, the gut is the first target for mycotoxin toxicity, but it is also the site of the absorption of mycotoxins that leads to systemic exposure to these compounds. The most frequent mechanism is chemical transformation of mycotoxins by enzymes present in the microbe cells, or excreted by the microbe cells into the gut.

Figure 1: Mycotoxin and gut microbiota interactions.

Indeed, although transformation of DON into DOM-1 by the pig microbiota has been characterized, degradation was poorly effective or occurred in the last portion of the intestine and excreta, i.e., of the fraction of the toxin that was not absorbed in the small intestine. The main reason for the interest in the microbial degradation of mycotoxins in ruminants is the fact that the transformation occurs in the rumen, before absorption of mycotoxins in the small intestine. Consequently, ruminant species are among the most resistant animal species to DON, while pig is the most sensitive.

Whatever the mechanism involved in the effect of mycotoxins on gut microbiota, its consequence changes the population equilibrium, which can lead to dysbiosis. Changes in the health status corresponding to these alterations can be responsible for bacterial translocation and for the onset of infectious diseases. Dysbiosis is also considered to play a key role in several chronic human diseases, including colorectal cancer, diabetes, and degenerative diseases of the nervous system.

The expression “masked mycotoxins” is used to characterize plant-derived mycotoxin metabolites, mainly glucose- and sulfate-conjugated forms, of DON, T2-toxin, and ZEN. The word masked is used to highlight the sequestration of these metabolites in the plant cell vacuole, which reduces their phytotoxicity. By extension, “masked” is also often used for conjugated mycotoxins formed in animal tissues. Because of their modified form, masked mycotoxins are not detected when dosing the parent compound using conventional analytical techniques.

Observation of anaerobic de-epoxydation of DON into DOM1 in ruminant species opened the door to different defense strategies against mycotoxins that aimed to degrade the mycotoxin prior to its absorption in the gut, using purified microorganisms or enzymes added to the feed.

A recent review of the origin of bacteria involved in the degradation of DON reported that around half originated from the gut microbiota. Other Gram-positive bacterial strains used as mycotoxin-biotransforming agents belong to the genera Bacillus, Nocardia, Corynebacterium, Mycobacteria, Rhodococcus, and Curtobacterium. Gram-negative aerobic bacteria from the genera Flavobacterium, Pseudomonas, and Alcaligenes, but also fungi and yeasts, such as Saccharomyces cerevisiae, were shown to have the potential ability to biodegrade mycotoxins.

Several pathogens can develop in the gut, and some can cross the gut barrier and invade the body. Defense against pathogens, i.e., the gut barrier effect, is the result of the synergy of three complementary mechanisms/barriers: (1) a microbiota barrier formed by non-pathogenic microbes that colonize the gut; (2) a physical-chemical barrier formed by the epithelial cells and their secretions; and (3) an immune barrier formed by the GALT. Alterations to the gut barrier function lead to mucosal infection or translocation of bacteria and their products, namely pathogen-associated molecular patterns, to the whole body.

The interactions between mycotoxins and gut microbiota were revealed very early on. Some of the differences in sensitivity in different animal species were thus explained by a protective effect of the microbiota against mycotoxin toxicity. This effect was associated with the degradation of the molecules into less toxic metabolites and a reduction in digestive absorption of mycotoxins. The characterization of the microbes involved in these reactions enabled the development of probiotics, and some of the currently sold probiotics derive directly from animal digestive flora. In parallel to this beneficial effect of the microbiota on the toxicokinetics of mycotoxins, a negative effect was recently demonstrated in the form of the hydrolysis of conjugated/masked mycotoxins. This hydrolysis, also related to gastric acidity and digestive enzymes, led to the release of mycotoxins in the digestive tract, which, added to the non-conjugated forms, contributed to the overall toxicity of contaminated food and feed.