How Your Gut Microbiome Affects Your Mood
They cut one nerve in a mouse, and a calming microbe stopped working. So what is your gut telling your brain right now?
Transcript
A lab bench in Hamilton, Ontario. Under the lamp there's a short length of mouse intestine, still alive in a bath of fluid, a tiny river running through the middle of it. No animal attached. No brain. Just a gut, and a wire clipped to the nerve fibers leaving it... the ones that travel up toward the head. A researcher drips in a dose of bacteria. And the nerve starts firing faster. Which is an unsettling thing to hear about, sitting in the body you're sitting in. Because you have that same wiring. Something living in your intestines, that never touches your brain, sending signals up a cable toward it. And to prove that cable was the messenger, somebody had to cut it. Hold on to that. We'll get there. Rewind to twenty eleven. University College Cork and McMaster University, a team led by Javier Bravo with John Cryan and John Bienenstock, publish in the Proceedings of the National Academy of Sciences. And the setup sounds almost insultingly simple. Take healthy mice. Feed them a broth containing one bacterium. Lactobacillus rhamnosus, strain J B one... a cousin of what's floating in your yogurt. Then watch what those mice do when life gets hard. The fed mice look calmer. Less anxious behavior. Less of that give-up, float-in-place despair researchers use as a stand-in for depression. Stress them, and their bodies pump out less corticosterone... the rodent version of the stress hormone flooding you before a big meeting. And then the researchers look inside the skulls. The receptors for GABA, the brain's main calming signal, have CHANGED. In the hippocampus. The amygdala. The prefrontal cortex. Not the gut. The brain. Rewired from a bug that never left the intestine. So how does the message get out? There's a nerve called the vagus. It's the main cable between your gut and your brainstem, and it's running traffic in both directions right now, whether you notice or not. So the Cork team did the brutal, elegant thing. One group of mice... they cut that cable, below the diaphragm. Then fed them the exact same bacteria. Nothing. No calmer behavior. No change in brain chemistry. The effect didn't shrink. It vanished. Which is how we end up back at that piece of gut on the bench. Two years later the McMaster group didn't want to infer the message anymore. They wanted to HEAR it. So they cannulated mouse intestine outside the body, perfused the inside and the outside separately, and recorded the electrical spikes running up the vagal fibers. Add bacteria to the inside of the tube... and the firing speeds up. They titled that paper psychoactive bacteria. Not a metaphor. A bug, talking, in the only language a nerve understands. Now. Mice are not you. So in twenty sixteen, John Kelly and colleagues in Cork tried something that still makes me sit back in my chair. They took gut bacteria from people living with depression... and transplanted them into rats whose own microbes had been stripped out. These rats never met a sad human. They didn't lose a job, or a partner, or a Tuesday. And they developed anhedonia. The loss of pleasure. Plus anxiety-like behavior, inflammation, shifts in tryptophan. Zheng and colleagues found the same thing that same year, in germ-free mice. Then, in Belgium, a quieter kind of evidence. Mireia Valles-Colomer and Jeroen Raes went through the Flemish Gut Flora Project. Over one thousand people. Their stool, and their mental health. Two groups of bacteria, Faecalibacterium and Coprococcus, both butyrate makers, tracked with higher quality of life. And Coprococcus, along with a microbe called Dialister, was depleted in people with depression... even after accounting for antidepressants. Then the team catalogued which gut microbes can make brain-active chemicals. Some of them make GABA. The same calming signal. And here's the honest part, because this stuff gets oversold in supermarket aisles. Nearly all the cause-and-effect work is in rodents. The human studies are snapshots... association, not proof. And the arrow could point the other way, easily. Depression changes how you eat, how you sleep, how your gut moves, and all of that reshapes who's living down there. So no. A probiotic drink is not an antidepressant. Anyone selling you that is about a decade ahead of the science. But this part is true right now, while you listen. Your vagus nerve is carrying traffic upward from a dark, crowded, chattering ecosystem that you personally feed several times a day. Most of that conversation you will never consciously hear. You'll just experience it as a mood. As a Tuesday that feels heavier than it should. We spent centuries assuming feelings came from above the neck. It turns out some of the vote may be cast from below it. You are not carrying passengers. You're carrying correspondents.
Sources
Katy and Theo researched this episode from these sources.
- Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve (PNAS, 2011)
- Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents (AJP-GI)
- Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat (Journal of Psychiatric Research, 2016)
- The neuroactive potential of the human gut microbiota in quality of life and depression (Nature Microbiology, 2019)