**4. Mycotoxin Consumption and Human Gastrointestinal Diseases**

The multidirectional adverse effects of mycotoxins on the GI tract (Table 2) cause that exposure to these substances may result in various disturbances of the GI activity in humans. However, the common prevalence of mycotoxins in the human environment and food indicates that participation of these chemicals in the development of intestinal diseases in humans may be an important public health problem all over the world [208].


**Table 2.** Gastrointestinal signs and effects of mycotoxins on the gastrointestinal tract.


**Table 2.** *Cont.*


**Table 2.** *Cont.*

The impact of mycotoxins on the intestinal barrier functions, intestinal immunity, secretory activity and gut microflora, as well as their genotoxic/mutagenic and carcinogenic effects are mainly known from experimental studies (Table 2). Such studies do not always fully reflect the conditions of natural exposure to mycotoxins. The first problem is the dose of mycotoxins, which is very difficult to determine in the human diet [254,255]. The second, more important, problem is the fact that food may contain several or even a dozen mycotoxins at the same time. These mycotoxins may chemically interact with each other, which leads to changes in their toxic properties and bio-availability. In this case, synergistic interactions between mycotoxins is particularly dangerous [255,256]. For example, previous studies have shown that mixtures of ZEN and DON or DON, T2 and ZEN show higher toxicity than these individual mycotoxins [175,257]. Moreover, it is known that human food may also contain other active substances and contaminations, such as bacterial products, pesticides, phytotoxins, chemical contaminations and preservatives, which not only affect mycotoxin activity but may contribute to various disorders in the GI tract [258]. That is why it is so difficult to determine the effective participation of mycotoxins in the development of human gastrointestinal diseases.

A comparison of histopathological changes occurring in the GI tract during human gastrointestinal diseases and changes in the intestine caused by mycotoxins has shown that the negative development in the GI tract in both cases are similar [255]. This may suggest a correlation between a degree of exposure to mycotoxins and the risk of human gastrointestinal diseases, as well as the participation of mycotoxins in the development of various diseases, including inflammatory bowel disease, Crohn's disease, coeliac disease and colorectal cancer [255]. However, only comprehensive epidemiological studies on the relationships between mycotoxin levels in food, blood and urine and the occurrence of particular diseases conducted on a large human population would explain the connection between exposure to mycotoxins and the risk of human gastrointestinal diseases. Unfortunately, such studies are fragmentary and relatively few. These studies have reported that aflatoxins (especially aflatoxin B1) may pose a carcinogenic risk and exposure to these chemicals may increase the risk of gastric and colorectal cancer [259,260]. Other studies suggest a correlation between the exposure to ZEN and colorectal cancer [261], as well as relationships between exposure to aflatoxins and Crohn's Disease, coeliac disease and ulcerative colitis [262]. Despite this, differences in concentration of patulin and citrinin in plasma and urine between healthy people and patients suffering from colorectal cancer have not been observed, which may suggest that these mycotoxins are not key factors leading to this disease [263].

### **5. Conclusions**

Based on previous studies, it is known that mycotoxins affect the enteric nervous system (Table 3). This impact may be multidirectional and depends not only on the chemical structure of the mycotoxin and mammal species studied, but also on the type of the enteric plexuses and segment of the digestive tract. Mycotoxins may act on the size and morphological properties of intestinal nervous structures and the neurochemical character of the enteric neurons. These changes are probably a result of adaptive and protective reactions, which affect homeostasis maintenance. Moreover, mycotoxin-induced changes in the ENS are often the first sign of exposure to low doses of mycotoxins. Understanding the exact mechanisms connected with the influence of mycotoxins on the intestinal innervation may be very important in determining mycotoxin dose limits, which are safe and neutral for the living organism. Unfortunately, the current information about the influence of mycotoxins on the ENS is relatively limited and elucidation of all aspects connected with this issue requires further research.


**Table 3.** Influence of mycotoxins on the enteric nervous system.


**Table 3.** *Cont.*

VIP—vasoactive intestinal polypeptide; CART—cocaine- and amphetamine-regulated transcript; CGRP—calcitonin gene related peptide; SP—substance P; NOS—nitric oxide synthase; PACAP—pituitary adenylate cyclase activating peptide; GAL—galanin.

**Author Contributions:** Conceptualization, S.G., M.G. and K.M.; supervision, S.G.; writing—original draft, S.G., M.G. and K.M.; writing—review and editing, S.G. All authors have read and agreed to the published version of the manuscript.

**Funding:** Project financially supported by Minister of Science and Higher Education in the range of the program entitled "Regional Initiative of Excellence" for the years 2019–2022: Project No. 010/RID/2018/19, amount of funding 12.000.000 PLN.

**Conflicts of Interest:** The authors declare that they have no conflict of interest.

### **References**


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