Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/13/2016
Publication Date: 12/16/2016
Publication URL: http://handle.nal.usda.gov/10113/5700690
Citation: Lam, T.L., Tam, C.C., Stanker, L.H., Cheng, L.W. 2016. Probiotic microorganisms inhibit epithelial cell internalization of botulinum neurotoxin serotype A. Toxins. 8(12):377. doi: 10.3390/toxins8120377.
Interpretive Summary: Botulinum neurotoxins (BoNT) are some of the most potent biological toxins. Thus far, the only treatments available are intensive medical care and the administration of an equine antitoxin. Probiotic bacteria are beneficial bacterial that have been shown to prevent certain pathogenic bacteria from colonizing the human intestines. In this study, we investigated whether the application of probiotic bacteria could inhibit the binding and uptake of botulinum neurotoxin serotype A in human intestinal epithelial cells. Four probiotic bacteria tested showed dose dependent inhibition of BoNT cells binding. Probiotic bacteria could be a new front of treatment or prevention strategy for human botulism.
Technical Abstract: Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that BoNT serotype A (BoNT/A) complex (holotoxin with neurotoxin-associated proteins) bind and transit through the intestinal epithelia to disseminate in the blood faster than BoNT/A holotoxin alone [Lam et al 2015]. Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins [Rao and Samak 2013; Bermudez-Brito M et al 2012]. We wanted to evaluate whether probiotic microorganisms will block BoNT/A uptake in the in vitro cell culture system using Caco-2 cells. Probiotic bacteria (Saccharomyces boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus LGG, and Lactobacillus reuteri) were able to block BoNT/A uptake in a dose-dependent manner whereas a non-probiotic strain (Escherichia coli) did not. We also show that inhibition of BoNT/A uptake was not due to the degradation of BoNT/A nor by sequestration of toxin via binding to probiotics. These results show for the first time that probiotic treatment can inhibit BoNT/A internalization in vitro and probiotic binding to BoNT/A receptor(s) may be the mechanism involved which may lead to development of new therapies.