“We might end up being able to correct a behavioral deficiency by what we put in a milkshake.”
THE EVIDENCE FOR A CONNECTION between gut health and brain health is becoming increasingly hard to ignore. A new study adds to the mountain: In the paper, a team of scientists at Baylor College of Medicine link gut bacteria to specific brain conditions.
But beyond this, the team may have unlocked how to leverage the connection to treat brain conditions that affect social behavior.
WHAT’S NEW — The new research suggests hacking that connection via the vagus nerve by changing the composition of microbes in the gut. This nerve functions as a kind of fiber-optic cable that carries messages between the gut and the brain. Specifically, the team behind this paper looked at the microbiome’s role in hyperactivity seen in mice lacking a gene associated with autism. What they found suggests that altering the population of gut microbiota through food may in turn alter behavior.
HERE’S THE BACKGROUND — The paper zeroes in on the gut microbiome, which is the name given to the diverse world of tiny, organisms which live in our guts, including bacteria, viruses, protozoa, and even fungi.
Mauro Costa-Mattioli is a professor and Cullen Foundation Endowed Chair in Neuroscience and director of the Memory and Brain Research Center at Baylor College of Medicine. Together with his colleagues, he discovered new evidence to suggest different behaviors are independently regulated by both genes and the microbiome.
“When you have a genetic disorder, you have a mutation in the genes. And that mutation affects the brain to cause one particular symptom in the brain, in this case, hyperactivity. But the mutation that causes that symptom isn’t just in the brain, it affects every single cell of your body,” Costa-Mattioli tells Inverse.
The living organisms found in our gut generate metabolites, which are carried as sensory information to the brain via the vagus nerve. If there are deficiencies in the microbiome, the signals carried to the brain via the vagus nerve may be disrupted, inhibiting brain activity. This, Costa-Mattioli says, can in turn cause social behavior problems.
Costa-Mattioli and his colleagues posed a new hypothesis: If you can modulate the microbiome through diet to rebalance gut flora, will the signals between the gut and the brain also even out?
HOW IT WORKS — Costa-Mattioli likens the situation to a city in which all but one neighborhood has power.
“No matter what you do, this one neighborhood doesn’t have power. But you have an extension cord and a power supply,” he says — in this analogy, the vagus nerve functions as the extension cord from the “power supply” in the gut’s biome.
“By turning that power supply on, now the extension cord can bring power to that neighborhood, and now you have a functioning circuit,” he says.
In this paper, the researchers show how introducing a specific species of bacteria — in this case a probiotic called L. reuteri — into mice’s water makes it a part of the mouse’s microbiome. Once entrenched in the murine gut, these bacteria then generated the appropriate metabolites to be carried to the brain.
Using their method, the researchers found treated mice showed elevated levels of oxytocin — the hormone associated with pleasure and bonding — in the reward area of the brain. Concurrently, the mice showed greater levels of social behavior than before treatment, according to the paper.
With this treatment, “the social experience becomes rewarding when you socialize,” Costa-Mattioli says.
WHY IT MATTERS — While it isn’t true that every single microbe in your gut may potentially be used as a therapy, “there are a bunch that you can [use],” he says. “And they are super safe and beneficial.”
If scientists can identify and isolate the specific microbes involved in brain development and function, then ostensibly they could one day develop special foods laden with the microbes which alter brain function — and behavior. These food fixes won’t be able to change a person’s genetics, but they may be able to alter the behavior that can stem from genetic conditions which affect the brain.
WHAT’S NEXT — One advantage of this kind of therapy is how safe and inexpensive it is to produce. We know these microbes are safe, for example, because most people in the world are walking around with them inside their gut right now. A way to think about this style of therapy is in the same way as everyday nutritional deficiencies — it would not be unlike an anemic person eating iron-rich foods to build up iron in the blood. Right now, these promising results are in mice — and humans are not mice. In Italy, a small, preliminary clinical trial testing supplementation L. reuteriin autistic children is ongoing.
If these preliminary results bear out in a human trial, the results will be “life-changing” Costa-Mattioli says.
“If this ends up working as well in humans as it does in mice, we might end up being able to correct a behavioral deficiency by what we put in a milkshake.”
Abstract: The core symptoms of many neurological disorders have traditionally been thought to be caused by genetic variants affecting brain development and function. However, the gut microbiome, another important source of variation, can also influence specific behaviors. Thus, it is critical to unravel the contributions of host genetic variation, the microbiome, and their interactions to complex behaviors. Unexpectedly, we discovered that different maladaptive behaviors are interdependently regulated by the microbiome and host genes in the Cntnap2−/− model for neurodevelopmental disorders. The hyperactivity phenotype of Cntnap2−/−mice is caused by host genetics, whereas the social-behavior phenotype is mediated by the gut microbiome. Interestingly, specific microbial intervention selectively rescued the social deficits in Cntnap2−/−mice through upregulation of metabolites in the tetrahydrobiopterin synthesis pathway. Our findings that behavioral abnormalities could have distinct origins (host genetic versus microbial) may change the way we think about neurological disorders and how to treat them.