Aflatoxin B1 exposure disrupts the intestinal immune function via a soluble epoxide hydrolase-mediated manner

Aflatoxin B1 (AFB1) contamination in food and feed leads to severe global health problems. Acting as the frontier immunological barrier, the intestinal mucosa is constantly challenged by exposure to foodborne toxins such as AFB1 via contaminated diets, but the detailed toxic mechanism and endogenous regulators of AFB1 toxicity are still unclear. Here, we showed that AFB1 disrupted intestinal immune function by suppressing macrophages, especially M2 macrophages, and antimicrobial peptide-secreting Paneth cells. Using an oxylipinomics approach, we identified that AFB1 immunotoxicity is associated with decreased epoxy fatty acids, notably epoxyeicosa-trienoic acids, and increased soluble epoxide hydrolase (sEH) levels in the intestine. Furthermore, sEH deficiency or inhibition rescued the AFB1-compromised intestinal immunity by restoring M2 macrophages as well as Paneth cells and their-derived lysozyme and alpha-defensin-3 in mice. Altogether, our study demonstrates that AFB1 exposure impairs intestinal immunity, at least in part, in a sEH-mediated way. Moreover, the present study supports the potential application of pharmacological intervention by inhibiting the sEH enzyme in alleviating intestinal immunotoxicity and associated complications caused by AFB1 global contamination.

Automated summary

Aflatoxin B1 (AFB1) contamination in food and feed causes serious health problems worldwide. This study found that AFB1 disrupts intestinal immune function by suppressing macrophages, especially M2 macrophages, and antimicrobial peptide-secreting Paneth cells. The study also identified that AFB1 immunotoxicity is associated with decreased epoxy fatty acids and increased soluble epoxide hydrolase (sEH) levels in the intestine. Furthermore, sEH deficiency or inhibition rescued the compromised intestinal immunity caused by AFB1 exposure. Overall, this study demonstrates the potential application of inhibiting the sEH enzyme to alleviate AFB1-induced intestinal immunotoxicity.