[Mechanism of intestinal absorption of botulinum neurotoxin complex]

Nihon Saikingaku Zasshi. 2019;74(3):167-175. doi: 10.3412/jsb.74.167.
[Article in Japanese]


Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum and related species cause botulism, a neuroparalytic disease associated with a high mortality. BoNTs are always produced as large protein complexes (progenitor toxin complexes, PTCs) through association with non-toxic components (NAPs) including hemagglutinin (HA) and non-toxic non-hemagglutinin (NTNHA). Food-borne botulism is caused by the ingestion of PTCs. PTCs in the gastrointestinal tract cross the intestinal epithelial barrier, enter the blood stream, and reach the nerve endings, where BoNTs cleave the SNAREs required for vesicle fusion. Consequently, BoNTs inhibit neurotransmitter release and cause paralysis. To cause food-borne botulism, BoNTs must traverse the intestinal epithelial barrier. However, the mechanism used to cross this barrier remains unclear. Using an in vitro epithelial barrier system, we previously showed that the interaction of HA with E-cadherin results in disruption of tight junctions. Furthermore, we previously reported that microfold (M) cells in the follicle-associated epithelium (FAE) of mouse Peyer's patches (PPs) are major sites where type A1 BoNT breaches the intestinal epithelial barrier. Here, I would like to demonstrate an ingenious invasion mechanism of the BoNT complex.

Publication types

  • Review

MeSH terms

  • Animals
  • Botulinum Toxins / metabolism*
  • Cadherins
  • Cells, Cultured
  • Dogs
  • Epithelial Cells / metabolism*
  • Hemagglutinins
  • Humans
  • Intestinal Absorption*
  • Intestinal Mucosa / cytology*
  • Mice
  • Multiprotein Complexes / metabolism*
  • Nerve Endings / metabolism
  • Neuromuscular Junction / metabolism
  • Neurotoxins / metabolism*
  • Neurotransmitter Agents / metabolism
  • Peyer's Patches / metabolism
  • SNARE Proteins / metabolism


  • Cadherins
  • Hemagglutinins
  • Multiprotein Complexes
  • Neurotoxins
  • Neurotransmitter Agents
  • SNARE Proteins
  • Botulinum Toxins