Breaking down the microbiology world one bite at a time
Bacteria to lose weight: An on-the-nose approach
According to the World Health Organization report in 2022, 1 in 8 people were obese, and 43% of adults were overweight. It is no surprise then that the public narrative often discusses the “obesity epidemic,” as it can be classified as a disease or chronic condition. And the reality of today’s world is that many people struggle to lose weight due to societal and biological causes, like stress, cheap access to unhealthy food, lack of exercise, etc.
This explains why medicines to curb food intake are racking up millionaire profits, such as Novo Nordisk’s Wegovy, which hit the market in 2021 and is on track to generate billions by 2030. For a list of medications approved for weight management (in the US), refer to the National Institute of Health. However, these medications often come with side effects, and once they are stopped being used, people quickly gain back the weight they lost.
The human body naturally produces hormones like leptin, α-melanocyte-stimulating hormone (α-MSH), and brain-derived neurotrophic factor (BDNF) that act in the brain to regulate appetite and metabolism. Treatments with these hormones, however, do not have the desired effect. Our bodies have a layer of protection to stop unwanted molecules passing from the blood to the brain, also known as the blood-brain barrier (BBB). Researchers have now set their sights on the “nose” to find a suitable way for hormones to reach the brain.
Inside our nose, there is a small patch of skin known as the olfactory epithelium (OE), a thin layer of specialized tissue with neurons that are responsible for catching molecules that we breathe, informing our brain of their presence, and creating the sense of smell. Because a single neuron connects from the surface of the nose to the brain, the distance between the OE and the brain is very small. Harmless bacteria also live within the nose, and the researchers wanted to see if they could use one such bacteria to provide hormones that could get from the OE to the brain.
Finding the right bacteria for the job
To do this, researchers looked at several probiotic bacteria that can survive in the nose and the OE. The researchers performed the tests in mice, as they are easier to work with, introducing the bacteria with a simple nasal spray. They found that a specific bacterial strain, Lactobacillus plantarum (Lp) WCFS1, had a strong and lasting adhesion to the OE. This is because it has a group of proteins outside the membrane, called OppA proteins, that bind a specific type of sugar, heparan sulphate, present in the epithelial cells of the OE, which allows the bacteria to remain there for days.
Can secreted molecules get to the brain?
The goal was for the Lp bacteria to secrete hormones that would reach the brain. To see if this was possible, they engineered Lp to secrete a fluorescent protein and analyzed where it went. After 7 days, it got past the OE and into the brain. However, the protein was absent from the mice’s other organs, and the kidneys and intestines only eliminated it in trace amounts.
Top left: Lactobacillus plantarum is administered intranasally to mice.
Top middle: The bacterial surface proteins OppA bind to the OE cell sugars.
Top right: Payload delivery to the brain occurs by diffusion and transport from the OE.
Centre: Modified L. plantarum secrete payload molecules (in this case, hormones).
Bottom left: Fluorescent molecules were found to reach the olfactory bulb, in the brain.
Bottom right: Mice treated with the modified bacteria did not develop obesity with a high-fat diet.
Source: Graphical abstract of the main article (Shen et al., 2025)
Treating mice with hormones from Lactobacillus plantarum
The researchers engineered the bacteria to secrete either leptin, α-MSH, or BDNF. They then gave healthy mice access to a lot of fatty food. Normally, the mice eat a lot and develop obesity. Some mice were given daily treatment with normal Lp, and others with modified Lp to secrete one of the hormones, or a mix of Lp secreting all three hormones.
After 8 weeks, mice with Lp-secreting hormones had much less weight, while untreated mice and mice with unmodified Lp were obese. Mice treated with leptin-secreting Lp had the lowest food intake, least fat, and best glucose metabolism. They also tested a nasal spray of leptin directly. It helped manage weight and prevent obesity, but the leptin-secreting Lp had a stronger effect in every parameter tested.
From mice to man
Mice have a much more developed sense of smell than humans. Their OE takes about 50% of the nose’s inner surface, while in humans it is only 3%. Moreover, high amounts of bacteria in the nose over time can lead to polyps and other issues. The researchers acknowledged that their study cannot be translated to humans directly. However, their results are strong, finding a suitable candidate (Lp), evaluating the molecular mechanisms of bacterial adhesion to the OE, and engineering the bacteria, leading to successful weight management in mice.
Future steps might involve further engineering of bacteria to improve adhesion and finding more reliable ways of delivering leptin from the OE to the brain. Regardless, the modified probiotics approach is a promising new idea for weight management, which will surely be explored further because of the current importance and market share of weight management treatments.
Featured image: modified from Graphicpic https://www.graphicspic.com/product/causes-of-obesity-poster-with-7-element-infographic-steps-illustration-with-icon-vector/
micro-bites.org 