Mycotoxins
The intestinal barrier is one of the body’s first lines of defense against pathogens and external contaminants.
- Therefore, any alteration in its structure or function can trigger problems that may go unnoticed, but that in the long run can translate into important economic losses due to poor performance and the presence of diseases.
In this regard, numerous studies focus on the impact of exposure of the intestinal barrier to toxins, including mycotoxins – secondary metabolites produced by mycotoxigenic fungi that frequently present in feed ingredients.
- Although many of their health effects (cytotoxicity, mutagenicity, genotoxicity, carcinogenicity, reprotoxicity, immunotoxicity, hepatotoxicity, nephrotoxicity, etc.) have been extensively studied, much remains to be explored regarding the impact of mycotoxins on the integrity of the intestinal barrier and the balance of the intestinal microbiota.
Given the wide occurrence of mycotoxins in raw materials for animal feed, usually with several being found simultaneously, the digestive system is exposed to higher concentrations than other organs, and it is essential to know the mechanisms involved in the alterations of the intestinal barrier induced by these toxins.
THE DELICATE BALANCE OF THE INTESTINAL BARRIER
The intestinal barrier is essential for gastrointestinal health, being a multifaceted structure composed of different levels of protection.
These levels include physical, chemical, immune and microbial barriers that work together to maintain intestinal homeostasis and protect the body from harmful external agents.
PHYSICAL BARRIER
The intestinal epithelium plays a fundamental role in the formation of the physical barrier, being formed by enterocytes, goblet cells, Paneth cells and enteroendocrine cells distributed in a single layer that covers the surface of the intestine.
- These cells are interconnected by adherens junctions and tight junctions that regulate the permeability of this physical barrier.
Tight junctions are particularly important in the regulation of intestinal paracellular permeability, which contributes significantly to barrier integrity.
CHEMICAL BARRIER
Represented mainly by the mucus layer that lines the surface of the intestine.
This mucus layer is composed mainly of mucins and antimicrobial proteins produced by goblet cells and Paneth cells. Its main function is:
- Avoid direct contact of luminal bacteria with the intestinal epithelium.
- Facilitate nutrient absorption.
IMMUNITY BARRIER
It plays a crucial role in the protection of the intestine, being composed of immune cells located in the lamina propria, such as intraepithelial lymphocytes, Paneth cells and IgA-secreting plasma cells, as well as immune mediators such as IgA and cytokines.
- These components help regulate the gut’s immune response and prevent inflammation.
MICROBIAL BARRIER
Represented by the intestinal microbiota, composed of a wide variety of microorganisms, playing a crucial role in intestinal health through their protective, metabolic and structural functions.
- However, microbial imbalance can lead to intestinal inflammation and intestinal barrier dysfunction.
LOWER INTESTINE, UNDER SIEGE FROM MYCOTOXINS
Several in vitro and in vivo studies have been carried out showing the detrimental effects of intestinal barrier exposure to mycotoxins, especially those most frequently found (aflatoxins -AF-, zearalenone -ZEN-, ochratoxin A -OTA-, fumonisins -FB-, deoxynivalenol -DONand T-2 toxin), alone or in combination, in feed and food raw materials.
DESTROYING THE CHEMICAL BARRIER
In addition to affecting the physical barrier, mycotoxins also alter the intestinal chemical barrier, having been shown to modify the composition of intestinal mucin, thus altering its function.
- It has been observed that, even at low concentrations, mycotoxins are able to interfere with the mRNA expression of specific mucin proteins, leading to mucosal damage and intestinal inflammation.
Regarding the production of antimicrobial peptides, it has been shown that mycotoxins increase their production, with an increase in the expression of porcine defensins 1 and 2 having been observed.
In an in vitro study published in 2015, it was reported that Porcine beta-defensin 2 increased the expression of mucin mRNA in Caco-2 cells, deducing that, when the intestinal tract is damaged by mycotoxins, the secretion of antimicrobial peptides stimulated mucin production to improve the function of chemical barrier of the intestinal mucosa.
In this regard, numerous studies have pointed to the addition of antimicrobial peptides to feed as a strategy to antagonize mycotoxin toxicity.
Regarding the immune barrier, it has been observed that mycotoxins are able to stimulate the secretion of proinflammatory compounds, increasing intestinal permeability and facilitating the passage of toxins and pathogens into the bloodstream.
In conclusion, mycotoxins represent a silent threat to intestinal integrity, interfering with multiple aspects of the gastrointestinal barrier and unbalancing its optimal functioning.
- Through various mechanisms, these toxins compromise the structure and function of the intestinal barrier, which can lead to increased permeability, inflammation and microbial dysbiosis.
The intestinal barrier, composed of physical, chemical, immune and microbial barriers, is essential for maintaining intestinal homeostasis and protecting the body from
harmful agents.
- However, mycotoxins have the ability to affect each of these levels of protection, thus weakening the body’s natural defense against toxins and pathogens.
From decreasing transepithelial resistance to altering the composition of the intestinal microbiota, mycotoxins exert their influence in a wide and varied manner in the gut.
- In vitro and in vivo studies have shown how these toxins can alter the expression of tight junction proteins, modify mucin composition, stimulate the secretion of proinflammatory compounds, and alter microbial diversity, among other effects.
Consequently, it is critical to understand the precise mechanisms by which mycotoxins affect intestinal integrity and how these alterations contribute to disease predisposition and economic losses in animal production, and it is essential to implement prevention and mitigation strategies to reduce exposure to these toxins and protect animal health and welfare.
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