Intranasal Lactobacillus plantarum (Lp) naturally targets the olfactory epithelium (OE) in mice.
Lp efficiently releases therapeutic payloads in the OE, enabling transport to the brain.
Engineered Lp secreting appetite-regulating hormones reduces obesity in mice.
Lp-secreted Leptin shows longer-lasting effects than pure Leptin when delivered intranasally.
The intranasal route offers a direct pathway to the brain by bypassing the blood-brain barrier, yet its therapeutic potential has been limited by the olfactory epithelium’s (OE) anatomical and absorptive challenges. In this study, researchers harnessed Lactobacillus plantarum WCFS1 (Lp), a commensal bacterium with a natural affinity for the OE, and engineered it as a novel brain-targeted drug delivery system.
Upon intranasal administration, Lp effectively colonized the OE and released payload molecules that were transported into the brain. To validate its therapeutic potential, Lp was genetically modified to produce and secrete appetite-regulating hormones, including Leptin. In a mouse model of obesity prevention, intranasal delivery of engineered Lp led to:
Reduced appetite and body weight gain
Improved glucose metabolism
Decreased fat accumulation
Notably, Lp-secreted Leptin demonstrated sustained effects compared to pure Leptin, suggesting enhanced stability and prolonged action.
This study highlights Lp as a promising intranasal delivery vehicle for brain-targeted therapies, particularly for metabolic and neurological disorders. Its natural OE tropism, combined with genetic engineering capabilities, opens new avenues for non-invasive treatment strategies.
Could this approach revolutionize drug delivery for obesity and neurodegenerative diseases? Further research may pave the way for clinical applications.
Origial text link:https://www.cell.com/cell/fulltext/S0092-8674(25)00046-7