Botulinum toxin: a newly identified role in facilitating severe intestinal infections

Botulism  is a rare but potentially life‑threatening disease caused by botulinum neurotoxins (BoNT), produced by bacteria of the genus Clostridium. These toxins are widely recognized for their capacity to induce flaccid muscle paralysis by inhibiting the release of the neurotransmitter acetylcholine. In Europe, the most common form is foodborne botulism. However, emerging scientific evidence suggests that health effects of botulinum neurotoxins may extend beyond acute paralysis, suggesting a broader spectrum of biological and clinical impacts than previously understood.

A study conducted by the Departments of Biomedical Sciences and Molecular Medicine at the University of Padova, in collaboration with researchers from the Laboratory of Treviso of the IZSVe, has brought to light a previously underexplored aspect: even toxin levels too low to cause overt botulism can profoundly disrupt intestinal physiology, and facilitate infection by enteric bacteria such as Salmonella enterica and Shigella flexneri.

A study conducted by the Departments of Biomedical Sciences and Molecular Medicine at the University of Padova, in collaboration with researchers from the Laboratory of Treviso of the Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), has brought to light a previously underexplored aspect: even toxin levels too low to cause overt botulism can profoundly disrupt intestinal physiology and facilitate infection. The study was published in Science Advances.

The researchers found that “subclinical” doses of BoNT affect the enteric nervous system—the network of neurons that regulates intestinal function—by reducing peristalsis, i.e. the movements that propel luminal contents through the gut. This impairment slows intestinal transit, creating conditions that favour the persistence of pathogens and increasing their ability to breach the intestinal barrier.

Moreover, the toxins appear to compromise several of the intestine’s natural defence mechanisms: they weaken the local immune response, which is closely linked to cholinergic neurons, and reduce the production of mucin, a key component of the mucus layer that protects the mucosa from microbial attack. The study further demonstrated that these alterations facilitate infection by enteric bacteria such as Salmonella enterica and Shigella flexneri.

The findings broaden our understanding of the biological role of botulinum neurotoxins, indicating that they may contribute to the onset of intestinal infections even in the absence of the characteristic clinical manifestations of botulism. At the same time, they open new research avenues concerning the role of the enteric nervous system in intestinal defence mechanisms. BoNTs may, in fact, serve as valuable experimental tools for exploring the complex interactions among enteric neurons, the immune system, and the microbiota.

These findings invite us to consider botulinum toxin not only as the cause of an acute neurological disease, but also as a potential modulator of intestinal health.