Microbes in the gut do more than aid our digestion – they may also alter our mood. Elaine Hsiao and her team at Caltech have found that our intestinal bacteria can trigger gut cells to produce the neurotransmitter serotonin. They have published their findings in the journal Cell.
“This research may be a window to let us change serotonin levels to our advantage,” says John Furness, digestive physiologist at the University of Melbourne.
The microbes that line our gut, mostly bacteria, outnumber the body’s cells by 10 to one. Research into the scope and purpose of these complex bacterial colonies is relatively new. These bacteria have plenty of room to flourish – if your intestines were spread out flat they could cover the size of a standard boxing ring.
And their reach extends far beyond the bowel – it goes all the way to the brain. Scientists have known for years that mice stripped of their gut microbes are less social and more likely to become stressed. In 2013, Hsiao found a surprising association between autism and a particular strain of gut bacteria. Some gut microbes “could be truly mind-altering, affecting our brain development, function and even our behaviour,” she said in a 2013 TEDx talk.
Hsiao wanted to know if gut microbes manipulate the body’s levels of neurotransmitters – the chemical signals our nerve cells use to pass messages between each other. She started by looking at serotonin. Most people know it as the happy brain chemical, and some antidepressants work by maintaining high levels of serotonin in the brain. Yet more than 90% of the body’s serotonin is made in the digestive tract.
Serotonin keeps the conveyor belt in the intestine moving – it stimulates the nerves that tell the tube of muscle around your intestines to contract and relax, forcing the food down the process line.
If food stops moving through the intestine, microbes further down the line go hungry. One possibility is that microbes enhance our serotonin levels because it is in their best interest to keep food churning down the intestinal conveyor belt.
When Hsiao’s team compared the blood serotonin levels of mice with normal gut bacteria and microbe-free mice, they found the microbe-free cohort had 60% less serotonin. But when those microbe-free mice were recolonised with normal gut microbes, their serotonin levels went back to normal. The researchers identified 20 bacterial strains that contributed to the serotonin surge.
The bacteria don’t produce the serotonin directly. They release molecules called metabolites – including vitamin E – that prompt our own gut cells to make more serotonin. When these metabolites were given to microbe-free mice their serotonin levels replenished. Lead author Jessica Yano calls this “definitely exciting”.
Tweaking serotonin levels may do more than keep you regular – low serotonin levels in the blood have been linked to cardiovascular disease, osteoporosis and impaired blood clotting. So boosting a person’s gut population of serotonin-stimulating bacteria could help treat a range of ailments. But how can this be done? Yano says “it can be difficult to get particular microbes into the host to set up shop”. One day treatment could involve doctor’s bypassing bacteria altogether and prescribing a cocktail of bacterial metabolites.
And what about the brain, where serotonin helps regulate mood? Serotonin produced outside the brain cannot get into the brain because it cannot cross a layer of sentry cells know as the blood-brain barrier. But that’s not to say the bacteria in our gut can’t manipulate the mind.
Between your brain and gut (and its bacteria) runs the vagus nerve. Evidence that the brain and the gut are intimately connected has grown over recent years. A troubled brain sends signals to the gut – as we know when we feel “butterflies” in the stomach. The vagus nerve that links them is known to be stimulated by serotonin. The Caltech team is now investigating if bacterially boosted serotonin spikes can affect the brain and behaviour of mice.
Hsiao sees many possibilities: “What if we could, without a single invasive procedure, treat disorders like autism and depression?”