Translocation and dissemination of botulinum neurotoxin from the intestinal tract

Botulinum neurotoxins (BoNTs) are potent toxins which induce flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. They associate with non-toxic proteins (ANTPs or NAPs) to form complexes of various sizes which are resistant to acidic pH and protease degradation. BoNT trafficking from the digestive tract to the target neurons is still a matter of debate. BoNTs use different strategies to pass through the intestinal barrier including passage of BoNT complexes containing hemagglutinins (HAs) via M cells, HA-dependent perturbation of E-cadherin intercellular junctions between enterocytes and paracellular passage of BoNT complexes, and transcytosis of BoNT free of NAPs through certain intestinal epithelial cells. Then, BoNTs target neuronal cells, preferentially cholinergic neurons, in the intestinal mucosa and submucosa. The precise mode of BoNT dissemination until the final target neuro-muscular junctions is still elusive.