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

AFB1 exposure markedly alters gut microbiota composition, primarily by reducing the population of beneficial bacteria.

• AFB1 was administered orally, with the gastrointestinal tract identified as the primary site of contact.
• The study examined gut microbiota composition changes following AFB1 exposure in vivo.
• Reduction in beneficial bacterial populations was a key microbiota change observed.

AFB1 increases PTEN expression and suppresses the downstream PI3K/AKT signaling pathway in both jejunal tissue and IPEC-J2 cells.

• The PTEN/PI3K/AKT axis was examined both in vivo (jejunum) and in vitro (IPEC-J2 cells).
• Suppression of PI3K/AKT signaling was observed as a downstream consequence of increased PTEN expression.
• These signaling changes were associated with promotion of both apoptosis and necroptosis.

AFB1 promotes both apoptosis and necroptosis in jejunal epithelial cells via the PTEN/PI3K/AKT axis.

• Both apoptosis and necroptosis were identified as cell death mechanisms induced by AFB1.
• This represents a dual regulation of cell death pathways by AFB1 in intestinal epithelial cells.
• The study used both in vivo jejunal tissue and in vitro IPEC-J2 cell models to demonstrate these effects.

AFB1 impaired intestinal barrier function by decreasing expression of tight junction proteins ZO-1 and Occludin.

• ZO-1 and Occludin were specifically identified as tight junction proteins whose expression was reduced by AFB1.
• Reduced tight junction protein expression indicates disruption of the epithelial barrier.
• Intestinal barrier impairment was linked to the 'PTEN/PI3K/AKT-epithelial barrier' axis.

The PTEN-specific inhibitor VO-Ohpic effectively alleviates AFB1-induced changes in gut microbiota, cell death signaling, and intestinal barrier function.

• VO-Ohpic was used as a PTEN-specific inhibitor to confirm PTEN's key role in AFB1-induced intestinal damage.
• VO-Ohpic treatment alleviated changes in gut microbiota composition induced by AFB1.
• VO-Ohpic reversed AFB1-induced suppression of PI3K/AKT signaling, apoptosis, necroptosis, and decreased tight junction protein expression.
• The authors state this confirms PTEN's key role in mediating AFB1-induced intestinal injury.

This study is the first to elucidate the mechanism by which AFB1 induces intestinal damage through disrupting gut microbiota structure and the PTEN/PI3K/AKT-epithelial barrier axis.

• The authors claim novelty in identifying PTEN/PI3K/AKT as the mechanistic axis for AFB1-induced intestinal injury.
• The dual disruption of gut microbiota and PTEN/PI3K/AKT signaling represents a new mechanistic framework.
• The findings provide 'new targets and theoretical basis for the prevention and treatment of AFB1 poisoning.'