The idea that the gut and brain communicate has become a major focus of health research, but much of what scientists know about how that relationship might work comes from studies in animals. New research offers a closer look at the connection in people.
In a study of 61 healthy young women, published in Molecular Psychiatry, researchers found that certain functions the participants' gut microbes appeared capable of performing were associated with levels of two important brain chemicals, GABA and glutamate. The patterns differed depending on the part of the brain examined, suggesting that the gut-brain connection may be more complicated than a single signal traveling from one place to another. The study was observational, so it cannot show that gut microbes caused the differences in brain chemistry.
The study was supported through a research collaboration with FrieslandCampina, a Netherlands-based dairy company.
GABA and glutamate help regulate activity in the brain and are involved in functions including learning, thinking and emotional regulation. Researchers wanted to know whether differences in the gut microbiome might correspond with differences in those chemicals.
To investigate, they analyzed stool samples to identify genes carried by participants' gut microbes. Those genes gave researchers clues about what kinds of substances the microbes might be able to produce or break down.
They also used a type of brain scan to estimate GABA and glutamate levels in three areas of the brain. The researchers then looked for relationships between the two sets of measurements.
They found several.
Different microbial functions were associated with brain chemistry in different regions, rather than producing one consistent pattern throughout the brain. That regional variation was one of the study's more notable findings.
“The fact that different brain regions showed different relationships is particularly interesting,” said professor Kathrin Cohen Kadosh, senior author of the study. “It suggests that the gut–brain axis is not one simple pathway acting uniformly across the brain.”
Researchers also looked at participants' self-reported anxiety, depressive symptoms and sleep quality. Some microbial functions were associated with those measures as well, including pathways involving GABA, tryptophan and a short-chain fatty acid called propionate.
But those findings are especially preliminary. The study was small, the psychological analyses were exploratory and several associations did not hold up as strongly under more conservative statistical tests. The authors cautioned that the results need to be confirmed in larger studies.
There is another important limitation: researchers were looking at what the gut microbes had the genetic potential to do, not what they were actually doing at the time.
In other words, finding genes associated with the production or breakdown of certain compounds does not mean researchers directly measured those compounds being produced in the gut.
The study also cannot tell researchers which direction the relationship runs. Differences in the microbiome could potentially affect the brain, but brain activity, behavior, diet or other biological factors could also affect the microbiome. Some outside influences could affect both.
That distinction matters because the findings do not show that changing someone's gut bacteria would change their mood, sleep or brain chemistry.
“We are not saying that a particular gut bacterium causes anxiety or changes a particular brain chemical,” said lead author Dr. Nicola Johnstone.
The study population also limits how broadly the results can be applied. Participants were healthy women ages 17 to 25, and researchers did not directly control for factors including short-term dietary changes or menstrual cycle phase. The findings therefore cannot yet be assumed to apply to men, older adults or people with health conditions.
Still, the study moves the gut-brain conversation a little further into human research. Rather than showing simply that certain gut bacteria are more common in people with particular moods or behaviors, researchers were able to compare the microbiome with chemicals measured directly in the brain.
The next step is determining whether those relationships hold up in larger and more diverse groups and, eventually, whether deliberately changing the microbiome can actually change brain chemistry.
For now, the study adds evidence that the gut microbiome and brain may be connected in measurable ways, while leaving the much bigger question of cause and effect unanswered.