Illustration by Anna Kovecses
At any given moment, you have somewhere between 10 trillion and 100 trillion microorganisms inhabiting your gut — that’s more microbes in your bowels than there are cells in your body. If that isn’t impressive enough, consider that collectively these microbes have about 150 times as many genes as your own genome. Scientists are still trying to figure out exactly which microbes make up the human microbiome, but it’s estimated to contain more than 1,000 species and 7,000 distinct strains of bacteria. Your gut is never alone.
It’s also not working in isolation. What’s becoming more and more clear is that the microbes in the gut are crucial for the brain and mental health. Ted Dinan is an expert in this field, and he became so almost by accident. It was the early 2000s, and he’d recently taken a position at University College Cork, a place that he said was “known for its heavy-hitting microbiologists.” Some of these microbiologists were talking about a type of bacteria they described as “probiotic” — conferring some kind of health benefit. As a psychiatrist, Dinan thought it would be interesting to see what happened when he fed these probiotics to some rats he was studying in an experimental model of mental health. Lo and behold, rats given the probiotics expressed fewer signs of anxiety and depression. Dinan and his colleagues would go on to coin the term “psychobiotics” for microbes that can benefit the brain or behavior.
It’s the fourth (and final!) day of this week’s series on gut science. We’ve written about whether probiotics work, whether gut science is biased and why we’re so obsessed with constipation, and we’ve made a video about what poop can tell us about our health.
The idea that our intestinal tracts shape our mental states is hardly new. Medicine has a long history of blaming our guts for psychological disorders. In the early 1800s, an Army surgeon named William Beaumont became a pioneer in gastrointestinal physiology by studying gastric secretions, which he noted seemed to change in step with one’s moods. By the early 1900s, physicians and scientists had come to view the colon as the gateway to a wide array of mental illnesses and thought that microbes in the intestinal system might contribute to “fatigue, melancholia and the neuroses.”
The latest research shows that the digestive tract and the central nervous system maintain a complex two-way line of communication via the “gut-brain axis.” Studies where researchers manipulated the gut bacteria in mice have shown that these microbes influence how the brain develops, particularly the regions that influence the stress response and conditions related to stress, such as anxiety and depression, said Jane Foster, a neuroscientist at McMaster University. One recently published study found that the microbiome influences the regulation of genes related to myelin (a material that forms a sheath around nerves) in the prefrontal cortex, a part of the brain implicated in numerous psychiatric disorders, including depression and schizophrenia. The finding suggests a potential mechanism by which gut microbes could be involved in these conditions.
Bacteria in your intestines might also send chemical messages to your brain. Some strains of gut bacteria can secrete neurotransmitters such as acetylcholine, gamma-aminobutyric acid (GABA) and tryptophan. The enteric nervous system lining the digestive tract contains millions of neurons that can respond to these neurotransmitters and send signals up to the brain.
In one study, Dinan and his colleagues fed mice probiotics similar to those found in yogurt. Mice given the microbes behaved less anxiously and were more likely to venture into the open, exposed parts of a maze. They also had higher levels of GABA, which can be involved in anxiety and depression. These effects on the brain seem to involve signaling through the vagus nerve, which anatomically connects the guts and the brain, Dinan said. “When we severed the vagus nerve in animals, we got no impact from the bug at all,” he said, referring to the probiotic. In another study, another team of researchers transplanted microbes from the guts of one strain of mice to another and found that the second group displayed behavioral traits of the mice from which they’d received the microbes. Mice that had previously been hesitant to wander were more interested in exploring after their guts were exposed to microbiota of mice who were less inhibited.
Animal studies like these seem exciting, but at the moment, they’re about all we have, and the scientific literature is riddled with examples of mouse models that don’t end up applying to humans. A systematic review published in October looked at psychobiotic research on people and concluded, “There is very limited evidence for the efficacy of probiotic interventions in psychological outcomes.” Most of the studies done on humans so far have looked at differences in the microbial composition of healthy people versus those with a particular condition. “That’s what’s necessary before you can start to consider the mechanisms,” Foster said, but these studies don’t prove causality. Dinan’s group recently submitted a study for publication suggesting that a particular strain of probiotic seemed to help soothe anxiety in people, but it’s just a single study, and Dinan said he’s “very reluctant” to overstate the evidence so far.
This absence of evidence isn’t proof that psychobiotics don’t work in humans — instead, it reflects the fact that the gut-brain axis is a complicated system that’s hard to study. For instance, figuring out which organisms in the gut are important is a crucial step in understanding the system, but sampling them is hard, said Jonathan Eisen, a professor of evolution and ecology at the University of California, Davis. If altering the gut’s microbes can change behavior, which microbes are most important, and what does it take to tip the scales toward the right ones? We simply don’t have good answers yet.
There’s little doubt that changing your diet changes the microbiome in your gut. “What’s debatable is whether or not you can guide your microbiome in a direction that will have benefits,” Eisen said. Research has shown that people with certain health characteristics or disease have particular microbes, but that doesn’t tell us with any certainty that those microbes have any causative relationship with those traits. As author Ed Yong wrote a few years back, there is no “normal” or “healthy” microbiome that one should aim for. “The microbiome is complex, varied, ever changing and context-dependent.”
“Too many large-scale, spurious claims are being made,” Dinan said, mostly by people with something to sell. Although we have “very good data” from animal studies, he said, there’s nothing that could be described as solid clinical data linking the gut microbiome to depression or anxiety in people. This hasn’t stopped people from making outrageous microbiome-related promises. Eisen regularly calls out unscientific claims on his blog by awarding them “Overselling the Microbiome” awards. One award debunked the idea that antibiotics are “extinguishing” our microbiomes, and another called out the claim that changing your gut bacteria can prevent a stroke.
Eisen probably hasn’t given out his last “Overselling” award. Microbiome research is hot right now — the National Institute of Mental Health has awarded $3.7 million in grants for 2015 and 2016 to study the microbiome’s role in mental health, the U.S. Office of Naval Research is also funding research on the issue, and a European project called MyNewGut is investigating the gut-brain connection. It’s clear that scientists are on to something interesting, but some patience is in order.
Biomedicine, after all, has a history of grandiose expectations about what new lines of study might yield. When the Human Genome Project was launched more than 25 years ago, it was widely hoped that it would lead to cures for many genetic diseases. That hasn’t happened, at least not on a large scale. After the genome, the epigenome — the chemical modifications that influence how genes function — became the hot new thing. Now the microbiome has taken on the same aura of expectation. But before we assume it will explain everything, we’d be wise to remember that biology is rarely as simple as we want it to be.