Gut Microbiome Plays a Direct Role in Shaping Brain Function and Evolution

A groundbreaking new study reveals that changes to the gut microbiome can change the way the brain works.

Humans have the largest relative brain size of any primate, but little is known about how mammals with larger brains evolved to meet the intense energy demands required to support brain growth and maintenance.

A new study from Northwestern University provides the first empirical data showing the direct role the gut microbiome plays in shaping differences in the way the brain functions across different primate species.

Our study shows that microbes are acting on traits that are relevant to our understanding of evolution, and particularly the evolution of human brains."

Katie Amato, associate professor of biological anthropology and principal investigator of the study

The study builds upon previous findings from Amato's lab that showed the microbes of larger-brained primates, when introduced in host mice, produced more metabolic energy in the microbiome of the host - a prerequisite for larger brains, which are energetically costly to develop and function. This time, the researchers wanted to look at the brain itself to see if the microbes from different primates with different relative brain sizes would change how the brains of host mice functioned.

What They Found

In a controlled lab experiment, the researchers implanted gut microbes from two large-brain primate species (human and squirrel monkey) and one small-brain primate species (macaque) into microbe-free mice.

Within eight weeks of making changes to the hosts' microbiomes, they observed that the brains of mice with microbes from small-brain primates were indeed working differently than the brains of mice with microbes from large-brain primates.

In the mice with large-brain primate microbes, the researchers found increased expression of genes associated with energy production and synaptic plasticity, the physical process of learning in the brain. In the mice with smaller-brain primate microbes, there was less expression of these processes.

"What was super interesting is we were able to compare data we had from the brains of the host mice with data from actual macaque and human brains, and to our surprise, many of the patterns we saw in brain gene expression of the mice were the same patterns seen in the actual primates themselves," Amato said. "In other words, we were able to make the brains of mice look like the brains of the actual primates the microbes came from."

Another surprising discovery the researchers made was a pattern of gene expression associated with ADHD, schizophrenia, bipolar and autism in the genes of the mice with the microbes from smaller-brained primates.

While there is existing evidence showing correlations between conditions like autism and the composition of the gut microbiome, there is a lack of data showing the gut microbes contribute to these conditions.

"This study provides more evidence that microbes may causally contribute to these disorders -specifically, the gut microbiome is shaping brain function during development," Amato said. "Based on our findings, we can speculate that if the human brain is exposed to the actions of the 'wrong' microbes, its development will change, and we will see symptoms of these disorders, i.e., if you don't get exposed to the 'right' human microbes in early life, your brain will work differently, and this may lead to symptoms of these conditions."

Implications and Next Steps

Amato sees clinical implications for further exploration of the origins of some psychological disorders and for taking an evolutionary perspective on the way microbes affect brain physiology.

"It's interesting to think about brain development in species and individuals and investigating whether we can look at cross-sectional, cross-species differences in patterns and discover rules for the way microbes are interacting with the brain, and whether the rules can be translated into development as well.

"Primate gut microbiota induce evolutionarily salient changes in mouse neurodevelopment" will be published by the Proceedings of the National Academy of Sciences of the United States of America.