Botulism, even minimal doses of toxin can induce intestinal infections
05.03.2026
Very low amounts of botulinum neurotoxins, insufficient to cause the typical paralysis of botulism, can nevertheless weaken the intestine's defences and promote bacterial infections. This emerges from a study by a team from the Department of Biomedical Sciences at the University of Padua, published in «Science Advances».
Botulism is a rare but potentially lethal disease caused by toxins produced by bacteria of the genus Clostridium, which can block the release of neurotransmitters and cause muscle paralysis. Due to their high danger, botulinum toxins are classified among agents with potential bioterrorism use. At the same time, their specific mode of action makes them valuable in medicine: they are used, in controlled doses, to treat dystonias, spasticity, hyperhidrosis, chronic migraine, overactive bladder, and also in aesthetic medicine.
According to Ornella Rossetto, professor at the Department of Biomedical Sciences at the University of Padua and co-corresponding author of the study, "botulinum toxins can enter neurons of the enteric nervous system, blocking the release of acetylcholine and thus altering functions fundamental for the defence of the intestinal mucosa." The effect, the researchers explain, particularly concerns the cholinergic neurons of the intestine: "Inhibition of enteric cholinergic neurons causes an alteration of intestinal peristalsis and reduces the release of protective mucus, thereby favouring infections by pathogenic bacteria such as Salmonella and Shigella."
Cesare Montecucco, emeritus professor at the University of Padua, and also co-corresponding author, recalls recent episodes: "As happened in cases recorded in Calabria and Sardinia in summer 2025, botulism manifests in groups of people who have shared food containing botulinum toxin." Montecucco describes three clinical profiles: severe cases with risk of death before diagnosis, those saved thanks to intensive care, and a third group with mild or very mild symptoms, mostly intestinal, often considered of little importance. But, he warns, "We have instead demonstrated that very low doses of botulinum toxin ingested with contaminated food can promote intestinal infections." Hence the call to carefully monitor patients with botulism after discharge and also those who have ingested minimal amounts, evaluating "appropriate antibiotic therapies to prevent the onset of intestinal infections."
The study also offers an interpretation for a frequent but little-considered symptom in botulinum intoxications: constipation. The alteration of intestinal peristalsis is interpreted as a direct consequence of the toxin's action on the enteric nervous system, often referred to as our "second brain."
For the first author Federico Fabris, post-doctoral fellow at at the Department of Biomedical Sciences at the University of Padua the results also require a revision of the classic disease model: "Until now, the intestine was considered mainly as an entry point for the toxin; our study shows instead that the intestine, and in particular the enteric nervous system, represents the first site of functional action of the toxin," with local effects that can increase susceptibility to infections.
The research, multidisciplinary in nature (neurobiology, microbiology, immunology and physiology), opens new perspectives on how botulinum neurotoxins can influence the balance between the organism and the gut microbiota even when they do not cause overt botulism.
