Bacteria in our gut may influence both our physical and mental health

If bacteria in your gut can affect your health, can they affect your brain, too?

Researchers are finding more and more evidence that the trillions of bacteria contained in our gut are sending signals to the brain and influencing behavior and cognitive functioning.

People in the fields of appetite and food intake have long known that the brain and the gut talk to one another, says researcher John Cryan, but a paper published 10 years ago in Japan made scientists take a new look at gut-brain communication. The paper revealed that mice lacking certain bacteria showed an increased stress response.

Cryan, who is chairman of the department of anatomy and neuroscience and principal investigator of the Alimentary Pharmabiotic Center at the University of College Cork in Cork, Ireland, says the paper made researchers in stress neurobiology ask an important new question: “What are bacteria doing that helps animals have a proper stress response?”

“We were interested in early life stress,” Cryan says, “and we showed, about five years ago, that if you were stressed early in life you have a lower diversity of your bacteria in your gut when you grow up — along with changes in your behavior.”

As recently as 20 years ago, Cryan says, researchers didn’t even believe that the immune system and the central nervous system had any important interactions. Demonstrating the interactions between the microbiome and the central nervous system “is a paradigm shift in how we're thinking about neuroscience,” he says.

“What we've come to appreciate is that the microbiome has an impact on almost every system we have,” Cryan says. “It's just that the brain has been one of the last frontiers in this regard. We still have to figure out the exact mechanisms of this communication — understanding how these systems work together to promote homeostasis.”

Sarkis Mazmanian, a professor of microbiology at Caltech in Pasadena, California, says scientists believe multiple mechanisms exist by which the gut can communicate with the brain.

Cryan’s research, Mazmanian points out, has already shown that bacteria can signal through the vagus nerve, which connects the enteric nervous system to the central nervous system. In addition, he says, metabolites, small molecules released by gut bacteria or by the gut itself in response to bacteria, can travel through the circulation and get into the central nervous system; larger microbial molecules may also get through the circulation into the central nervous system.

Finally, Mazmanian says, there is some preliminary evidence that immune cells can traffic between the gut and the central nervous system. Most of our immune cells — close to 70 percent — are in our digestive tract and they are constantly circulating from the digestive tract to other parts of the body. This area of research is fertile ground, he says, not just for looking at the gut-brain connection, but in terms of studying beneficial bacteria themselves.

“For many years, microbiologists have studied predominantly pathogenic bacteria, infectious agents. But in more recent years there's been an appreciation that beneficial organisms are not just benign or passing through our systems, but actually manipulating or controlling specific aspects of our biology,” he explains.

Cryan says researchers are starting to think about the function of the microbiome from an evolutionary perspective: Why has it evolved in this way? Why is there a mutualistic positive effect of bacteria on brain function, along with the negative?

Whether or not you can manipulate how you feel by keeping the bacteria in your gut happy is still an open question, but that’s the direction the field is moving in, Cryan says. Nevertheless, “we've a long way to go, and we have to manage expectations,’ he cautions.

“There is a lot of hype in the field … and we have to be clear that an awful lot of what we know is from animal studies or pre-clinical studies. There's very little human data out there yet. But I think it's a very exciting time in terms of understanding diet-microbe interactions that may have positive effects on mood.”

One of these exciting areas may be research into autism. For many years, parents of children with autism have sworn there is a very clear connection between the gut and the brain. Mazmanian's group recently published a study that suggests these parents may be on to something. There is some research, he says, showing the microbiome of autistic children is different than the “best-matched, normally developing controls.”

“That research has always been clouded by the fact that autistic children with GI issues are generally on restricted diets or specialized diets, and, of course, diet itself can change the microbiome,” Mazmanian says. “So it wasn't known if it was the autism that was causing changes in the microbiome or the diet intervention.”

In animal models of autism, Mazmanian’s group was able to duplitcate some of the gastrointestinal phenotypes shown in humans with autism, such as constipation and leakiness of the gut barrier. The mouse model indicates a link between changes in the microbiome and autism, he believes, because, though all the mice were on the same food, “the mice with behaviors consistent with human autism have these GI abnormalities similar to those in humans." 

Mazmanian took the research one step further and asked, ‘If there is this abnormal change in the microbiome, could we restore it through probiotics treatment?’

They used an organism from the human gut — not a commercially available probiotic — and introduced it to the “autistic-behaving mice.” They were able to restore both the behavioral and the GI deficits with this treatment.

Mazmanian cautions that these findings were only in mouse models, so “we need to take the research and the findings with a grain of salt.” Cryan too, cautions us not to get too far ahead of ourselves.

“The important thing I want to stress is that most bacteria will probably have no negative or positive effect on brain function. We need to be clear about that. We need to identify which ones are inducing positive effects — most won’t. That way, we can try to generate what we call psychobiotics, bacteria that will induce positive effects on mental health.”