PTEN/PI3K/AKT Axis Mediates Aflatoxin B1-Induced Intestinal Injury via Dual Regulation of Apoptosis and Necroptosis in Jejunal Epithelial Cells.

Aflatoxin B1 (AFB1), the most toxic and widely distributed aflatoxin, poses considerable health hazards to both animals and humans. Following oral intake, the gastrointestinal tract is the primary site of contact. Our study shows that AFB1 exposure markedly alters the gut microbiota composition, mainly by reducing the population of beneficial bacteria. It also increases PTEN expression and suppresses the downstream PI3K/AKT signaling pathway both in jejunal and IPEC-J2 cells, promoting apoptosis and necroptosis. In addition, AFB1 impaired intestinal barrier function by decreasing expression of ZO-1 and Occludin. Notably, the PTEN-specific inhibitor VO-Ohpic can effectively alleviate the above changes induced by AFB1, confirming PTEN's key role. Our study has first elucidated the mechanism by which AFB1 induces intestinal damage through disrupting gut microbiota structure and the "PTEN/PI3K/AKT─epithelial barrier" axis, providing new targets and theoretical basis for the prevention and treatment of AFB1 poisoning.