Abstract

Mycotoxins are fungal metabolites that occur in human foods and animal feeds, potentially threatening human and animal health. The intestine is considered as the first barrier against these external contaminants, and it consists of interconnected physical, chemical, immunological, and microbial barriers. In this context, based on in vitro, ex vivo, and in vivo models, we summarize the literature for compromised intestinal barrier issues caused by various mycotoxins, and we reviewed events related to disrupted intestinal integrity (physical barrier), thinned mucus layer (chemical barrier), imbalanced inflammatory factors (immunological barrier), and dysfunctional bacterial homeostasis (microbial barrier). We also provide important information on deoxynivalenol, a leading mycotoxin implicated in intestinal dysfunction, and other adverse intestinal effects induced by other mycotoxins, including aflatoxins and ochratoxin A. In addition, intestinal perturbations caused by mycotoxins may also contribute to the development of mycotoxicosis, including human chronic intestinal inflammatory diseases. Therefore, we provide a clear understanding of compromised intestinal barrier induced by mycotoxins, with a view to potentially develop innovative strategies to prevent and treat mycotoxicosis. In addition, because of increased combinatorial interactions between mycotoxins, we explore the interactive effects of multiple mycotoxins in this review.

Highlights

  • Mycotoxins are the non-enzymatic poisonous metabolites produced by fungi such as Aspergillus, Penicillium, and Fusarium genera [1,2]

  • TJs are multi-protein complexes, and they consist of different transmembrane connected to each other from the basolateral to apical direction through interconnected protein contacts, which consist of desmosomes, adherens junctions (AJs), and tight junctions (TJs) [22]

  • Major drawbacks exist for intestinal explants, thereby restricting their application. These include short-term preservation during culture and careful and laborious preparation [39,61]. While these limitations are technical in nature, ex vivo intestinal models are widely used to evaluate gastrointestinal toxicity induced by mycotoxins [68,69,70,71,72]

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Summary

Introduction

Mycotoxins are the non-enzymatic poisonous metabolites produced by fungi such as Aspergillus, Penicillium, and Fusarium genera [1,2]. Considerable attention has been given to several common mycotoxins, which affect both human and animal health, as well as economic growth. These include aflatoxins (AFs), ochratoxin A (OTA), deoxynivalenol (DON), fumonisins (FBs), zearalenone (ZEN), patulin (PAT), nivalenol (NIV), and citrinin (CTN) [4,5]. Mycotoxins have been classified into five groups by the International Agency for Research on Cancer. AFB1 and AFM1 are categorized as Group 1, which reflects their human carcinogen status. OTA and FB1 are classified as Group 2B carcinogens, whereas, DON, ZEN, PAT, and NIV are assigned to Group 3.

Components of the Intestinal Barrier
Limitations
In Vitro Intestine Model
Ex Vivo Intestine Model
In Vivo Intestine Model
Intestinal Dysfunction Induced by Mycotoxins
Effects of Mycotoxins on the Physical Barrier
Effects of Mycotoxins on the In Vitro Physical Barrier
Effects of Mycotoxins on the Ex Vivo Physical Barrier
Effects of Mycotoxins on the In Vivo Physical Barrier
Effects of Mycotoxins on the Chemical Barrier
Effects of Mycotoxins on the In Vitro Chemical Barrier
Effects of Mycotoxins on Ex Vivo and In Vivo Chemical Barriers
Effects of Mycotoxins on the Immunological Barrier
Effects of Mycotoxins on the In Vitro Immunological Barrier
Effects of Mycotoxins on the In Vivo Immunological Barrier
Effects of Mycotoxins on the Microbial Barrier
Effects of Mycotoxins on the In Vitro Microbial Barrier
Effects of Mycotoxins on the In Vivo Microbial Barrier
Contribution of a Leaky Gut to Intestinal Inflammatory Disease
Interactive Effects of Mycotoxins on Intestinal Barrier
Conclusions
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