From cellular stress to cytokine modulation: An in vitro study of intestinal effects of major Alternaria mycotoxins

Mycotoxins are frequently detected in food, making the gastrointestinal tract the first organ exposed. Here, we used various in vitro intestinal cell models to explore the barrier and immune responses to the Alternaria mycotoxins alternariol (AOH), alternariol methyl ether (AME), altenuene (ALT), altertoxin I (ATX-I), tentoxin (TEN), and tenuazonic acid (TeA). The mycotoxins exhibited low toxicity in undifferentiated Caco-2 cells, but AOH, AME, and ATX-I affected the cell cycle and reactive oxygen species (ROS) levels. None of the toxins alone or in combination with IL-1beta; had any effect on the barrier integrity or viability of the differentiated Caco-2/HT29-MTX-E12 co-culture. Furthermore, AOH and AME reduced IL-1beta-induced IL-8 secretion, whereas TeA increased the secretion, demonstrating immunomodulatory effects. For verification, we used the more in vivo-like EpiIntestinal TM model, which is based on human primary cells. AOH, AME, and TeA had minor effects on viability without compromising barrier integrity; also, cytokine secretion was less affected than in the co-culture model. Studies on uptake confirmed low absorption of AOH, AME, and TeA. Overall, the studies indicate a low absorption and moderate effects of the toxins on the gastrointestinal tract.