Do trichothecene mycotoxins disrupt intestinal epithelial barrier integrity and promote inflammation?

Trichothecene mycotoxins, such as deoxynivalenol, nivalenol, and T-2 toxin, are prevalent foodborne contaminants that pose significant risks to gastrointestinal health. Emerging research demonstrates their capacity to severely disrupt the intestinal mucosa and trigger robust inflammatory cascades.

Intestinal barrier disruption

• Permeability and Tight Junctions: Exposure to trichothecenes compromises the physical barrier of the gut, causing a sharp reduction in transepithelial electrical resistance (TEER) and a concomitant increase in paracellular permeability.
• Structural Damage: This barrier failure is driven by the down-regulation and redistribution of crucial sealing tight junction proteins, including occludin, claudin-1, claudin-3, claudin-4, and ZO-1, alongside the abnormal upregulation of pore-forming claudin-2.

Mechanistic pathways and inflammation

• Ribotoxic Stress: Trichothecenes bind directly to the 60S ribosomal subunit, halting translation and initiating a rapid ribotoxic stress response (RSR).
• MAPK and NF-κB Activation: This stress response activates mitogen-activated protein kinases (specifically p38, JNK, and ERK) and the NF-κB pathway.
• Cytokine Release: Activation of these cellular cascades drives the transcription and secretion of key pro-inflammatory cytokines, including TNF-α, IL-6, IL-8, IL-1β, and IL-18.
• Oxidative and ER Stress: The toxins induce mitochondrial reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress, which further stimulate the NLRP3 inflammasome, leading to enterocyte apoptosis and tissue-level inflammatory injury.

Bottom line

• Trichothecene mycotoxins directly compromise intestinal epithelial barrier integrity and promote localized inflammation by binding to ribosomes, activating MAPK and NF-κB signaling pathways, and downregulating critical tight junction proteins.