Humans have much larger brains than other primates, which need a lot of glucose to function. Scientists think changes in gut microbes (gut microbiota) may help meet this demand.
A study at Northwestern University tested this by giving germ-free mice gut microbes from three primate species with different brain sizes. The results showed that gut microbes can directly affect brain function.
This is the first clear experimental proof that the gut microbiome helps shape differences in brain function among primates.
“Our study shows that microbes are acting on traits that are relevant to our understanding of evolution, and particularly the evolution of human brains,” said Katie Amato, associate professor of biological anthropology and principal investigator of the study.
Human head shape genetics uncovered in new study
Earlier research from Amato’s lab found that gut microbes from primates with larger brains produce more energy when transplanted into mice. Since brains need a lot of fuel, this extra energy is essential for their growth and activity.
In the new study, scientists looked directly at the brain. They tested whether gut microbes from primates with different brain sizes could actually alter how mice’ brains functioned.
To test their idea, the researchers ran a controlled experiment. They gave germ-free mice gut microbes from two large-brain primates (humans and squirrel monkeys) and one small-brain primate (macaques).
Eight weeks later, the mice showed apparent differences in brain activity. Mice with microbes from small-brain primates showed different patterns of brain function than those with microbes from large-brain primates.
Excessive body fat around the middle linked to smaller brain size
In mice with large-brain microbes, genes involved in energy production and synaptic plasticity (learning) were more active. These pathways were far less active in mice with microbes from smaller-brained primates.
“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.”
The researchers found another surprising result. Mice given microbes from smaller-brained primates showed gene activity linked to conditions like ADHD, schizophrenia, bipolar disorder, and autism.
Past studies have shown connections between gut microbes and conditions such as autism, but clear proof that microbes play a direct role has been limited.
“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.”
Amato thinks these findings could be significant for medicine. They may help explain how some psychological disorders begin and offer new insights into how brain development has evolved.
“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.”
Journal Reference:
- Alex R. DeCasien, Jacob E. Aronoff, Elizabeth K. Mallott, Sahana Kuthyar, Sriram Chitta, Brian T. Layden, Maria L. Savo Sardaro, Stanton Gray, Lawrence E. Williams, Emma R. Liechty, Hyo M. Lee, Won Lee, James P. Curley, Christopher W. Kuzawa, Katherine R. Amato. Primate gut microbiota induce evolutionarily salient changes in mouse neurodevelopment. Proceedings of the National Academy of Sciences, 2026; 123 (2) DOI: 10.1073/pnas.2426232122
