Engineered Nasal Bacteria Deliver Appetite-Suppressing Hormones, Reducing Weight in Obese Mice

Researchers have recently reported in Cell that they successfully used nasal bacteria to deliver appetite-suppressing hormones to obese mice, leading to weight loss. Although this approach is still a long way from human application, it represents a promising example of using bacteria to more effectively transport drugs to their target sites in the body.

Typically, medications struggle to reach specific areas where they are needed, often resulting in unwanted side effects. By improving drug delivery systems, scientists hope to minimize these side effects by ensuring that therapeutic compounds are released precisely where they are most effective. Targeting the brain is particularly challenging due to the protective blood–brain barrier, which usually blocks microbes and certain molecules from entering.

To tackle this challenge, researchers from the National University of Singapore turned to a rarely explored route: the nasal passage. The first step involved identifying potentially useful microbes residing in the nasal cavity—a region that, despite its direct connection to the brain, remains relatively underexplored in terms of its microbiome.

The research team evaluated several bacterial strains, including five types of lactic acid bacteria that are generally recognized as safe. They screened these strains for their ability to bind to a molecule present in the olfactory epithelium, a mucosal tissue in the upper nasal passage linked to the brain via nerves critical for the sense of smell. Although bacteria themselves are unlikely to migrate from the nose to the brain, some molecules can diffuse along this pathway.

Ultimately, the scientists selected Lactobacillus plantarum and genetically engineered it to produce and secrete several molecules, including three hormones that regulate appetite. After administering daily doses of these engineered bacteria intranasally to obese mice over eight weeks, the mice exhibited reduced food intake and experienced weight loss during the treatment period.

While further research is necessary before this innovative method can be applied to humans, the study marks an important step toward more precise drug delivery using engineered bacteria, potentially paving the way for therapies with reduced side effects and enhanced efficacy.