Contamination of food and feed by mycotoxins is considered one of most serious food safety problems in the world, because these fungal metabolites can be teratogenic, mutagenic, carcinogenic and immunosuppressive, and can cause serious damages to animal and human health. Mycotoxins may modulate the gut microbiota with potential consequences for gut and host health. On the other hand, the gut microbiota may metabolize the mycotoxins thereby converting them to a form with different activity. Chemical-microbial interactions can be categorized into two classes: Microbiome Modulation of Toxicity (MMT) and Toxicant Modulation of the Microbiome (TMM). The present review provides a state-of-the-art overview of this bi-directional interaction between the major food-borne mycotoxins such as aflatoxins, ochratoxins, deoxynivalenols and zearalenone present in food, feed and the gut microbiota. In addition, the effect of probiotics on gut microbiota in animals exposed to mycotoxins is summarized. Possible consequences of the role of gut microbiota for the risk assessment of mycotoxins, are also discussed. It is concluded that without taking the role of the gut microbiota into account effects of food-borne mycotoxins on health may be underestimated.