Engineered commensal Nose bacteria can sneak drugs into the brain to reduce body weight/obesity by regulating the appetite

Amazing stuff! How about sniffing out obesity one sniff at a time! 😊

"Bacteria that colonize the nose have been engineered to ferry drugs to the brains of mice. Researchers examined bacteria in the nasal microbiome and identified the species Lactobacillus plantarum as both safe to use in treatment and able to bind to a molecule found on a nose membrane connected to the brain. They then engineered L. plantarum to produce and secrete three appetite-suppressing hormones. Obese mice that received a dose of the bacteria in their nose each day for eight weeks ate less and lost weight during the treatment period."

"... On 5 February, scientists reported in Cell that they have used nasal bacteria to deliver appetite-suppressing hormones to obese mice, which subsequently lost weight. Although the approach is still a long way from being used in humans, it is one of the latest examples of widespread efforts to harness bacteria to deliver drugs to where they are needed in the body more effectively. Another study, published today in Cell Systems, uses a different bacterial species to deliver a protective enzyme to skin cells. ..."

From the highlights and abstract:

"Highlights

• Intranasal Lactobacillus plantarum (Lp) targets the mouse olfactory epithelium (OE)

• Intranasal Lp releases payloads in the OE, facilitating transport to the brain

• Intranasal Lp-secreted appetite-regulating hormones reduce obesity in mice

• Lp-secreted Leptin shows sustained effects over pure Leptin when delivered intranasally

Summary

Intranasal administration through the olfactory epithelium (OE) presents a direct pathway for brain-targeted therapeutic delivery, although its feasibility is hampered by the anatomical and absorptive limitations of the OE.

In this study, we identified Lactobacillus plantarum WCFS1 (Lp), a commensal strain with a natural affinity for the OE and engineered it to function as a vector for cerebral drug delivery.

Upon intranasal administration, Lp released specific payload molecules within the OE, with subsequent transport and accumulation in the brain. The therapeutic efficacy of Lp was further validated by the recombinant production and secretion of appetite-regulating hormones. When administered intranasally in a murine model of obesity prevention, the engineered Lp significantly alleviated obesity-related symptoms. This was evidenced by decreased appetite, reduced body weight gain, and improved glucose metabolism and fat mass deposition. Our study demonstrates the capability of Lp as an intranasal delivery vehicle, emphasizing its potential for brain-targeted therapeutic applications."

Nature Briefing: Translational Research

Engineered nose bacteria sneak drugs into the brain "Microbes that reside peaceably in the nasal passageways and on the skin can be harnessed for taking drugs to target cells."

Engineered commensals for targeted nose-to-brain drug delivery (open access)

Graphical abstract