Intestinal molecular siphoning by engineered bacterial spores for non-systemic treatment of nicotine addiction

Eradicating toxic substances from the body often necessitates the use of therapeutic agents that circulate throughout the system and distribute to tissues, leading to unwanted side effects from unintended consequences. This research explores a novel approach called intestinal molecular siphoning, which aims to treat diseases caused by toxic substances by enzymatically breaking down the harmful compound in the intestinal lining.

This process drives the diffusion of the toxic substance from the bloodstream into the gut, enabling continuous elimination and alleviating dependence.

In this study, nicotine serves as a model toxic substance. Researchers engineered a live bacterial system using Bacillus subtilis spores coated with enteric layers for protection and targeted release in the gut. These spores displayed an enzyme that resistant to trypsin, which oxidizes nicotine. The bacteria were then administered orally to mice. The results demonstrated a significant reduction in nicotine levels in both blood and brain compared to control groups.

Beyond nicotine reduction, the live bacterial system effectively reduced addiction to nicotine. It achieved this by suppressing the surge of dopamine, which usually triggers reward responses, thereby alleviating withdrawal symptoms such as hyperalgesia. The system also prevented the upregulation of nicotinic acetylcholine receptors, reduced anxiety-like behaviors, and provided a non-systemic, enzyme-based therapeutic strategy to lower circulating toxic substances.