GoKawiil“I’ve been taking Ozempic to lose weight but now I want to go hiking and play badminton with my friends.” —Bob Janke
Source: Midjourney
Researchers rejoiced when Ozempic and other GLP-1 drugs worked to shed weight in their patients. But there was an unexpected bonus: Some depressed patients started to feel better. Researchers from Southeast University in China, led by Honghong Yao, think they know why. They pieced together several related observations to solve the mystery.
(I apologize in advance for a few gnarly bacterial names up ahead in this article. But the story is compelling, and you really don’t need to remember the names of the characters to appreciate the plot, so hang in there.)
GLP-1s and Your Gut: What's the Connection?
When GLP-1 drugs like Ozempic, Wegovy, and Trulicity are injected, they find their way to the gut. That’s not unexpected; GLP-1 drugs act on your gut to make you feel satiated. That’s where your body makes its own GLP-1, after all.
Yet one of the researchers’ most interesting findings is that people with major depressive disorder or anxiety tend to have significantly lower natural levels of GLP-1. That’s the first piece of the puzzle.
When tested on mice, GLP-1 drugs not only make them lose weight; they also reverse depression-like behavior. So, higher GLP-1 appears to act as an antidepressant, which fits well with the first puzzle piece. (Mice are not perfect proxies for people, but they are surprisingly useful when it comes to studies of depression and anxiety. Scientists are not supposed to anthropomorphize, but if you saw a mouse with “depression-like behavior,” you'd probably recognize it immediately. Still, mice are not humans, so keep that in mind.)
Every hormone the body releases has a receptor. That goes for GLP-1 as well. Its receptor is parsimoniously named GLP-1R. Interestingly, the researchers found that if they block GLP-1R, the mice don’t lose weight anymore—but they still reverse their depression. That means that whatever is causing the weight loss seems to be unrelated to the psychiatric change. That is a major plot twist, and a big puzzle piece.
Intriguingly, depression is not reversed in germ-free mice. Whatever GLP-1 is doing, it apparently has something to do with microbes. Without microbes, there is no antidepressant effect. The researchers then used genomic sequencing to see what impact the GLP-1 was having on the gut microbiome, and they discovered a significant enrichment of Lactobacillus delbrueckii. The final piece of the puzzle came in the shape of a microbe.
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