Scientists Put Human Gut Bacteria Into Mice and Found Their Brains Showed Primate-like Activity

The human brain is a greedy organ. It gulps energy, demands constant upkeep, and somehow grew far larger (relative to body size) than the brains of any other primate.

Scientists have always wondered how evolution paid that bill.

A new study from Northwestern University suggests part of the answer may be alive inside us. Our gut microbes, it turns out, don’t just help digest food. They may actively shape how brains develop and function across primate species.

By transplanting gut microbes from different primates into mice, researchers found that microbes alone could push mouse brains toward activity patterns seen in humans, squirrel monkeys, or macaques.

In other words, bacteria can make a mouse brain behave — at the genetic level — like the brain of a primate.

The Brain’s Hidden Energy Partner

Humans have the largest brain-to-body ratio of any primate. That comes as a cost since brains are expensive tissue from an energy standpoint. They burn a lot of calories nonstop, even at rest.

For perspective, the human brain, despite being only 2% of body weight, consumes about 20% of the body’s total energy, roughly 400-500 calories (or 1700-2100 kJ) per day

Evolutionary biologists have long debated how our ancestors afforded this upgrade. Ideas ranged from cooking food to eating more meat to shrinking other organs.

Now, microbes enter the story.

“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 at Northwestern University and lead author of the study.

Amato’s lab has spent years studying how gut microbes differ across primates. Earlier work showed that microbes from larger-brained primates produce more metabolic energy when placed in mice.

That finding hinted at a link. But it didn’t answer the bigger question: do microbes actually change how brains work?

This new study tackled that question head-on.

Turning Mice Into Microbial Testbeds

To isolate cause from coincidence, the researchers designed a tightly controlled experiment. They started with mice that had no gut microbes at all. Then they introduced gut bacteria from three primate species:

• Humans
• Squirrel monkeys (large-brained relative to body size)
• Macaques (smaller-brained relative to body size)

The mice lived with these microbes for eight weeks. Nothing else was changed.

After that, the team examined the mice’s brains. The differences were quite striking.

Mice that received microbes from large-brain primates showed patterns of brain activity unlike those seen in mice given macaque microbes.

The microbes didn’t just affect digestion or immunity, both well established functions. They altered the brain itself.

Genes That Power Learning and Flexibility

When researchers looked closely at brain tissue, they found that microbes from large-brain primates boosted activity in genes tied to energy production and synaptic plasticity.

Synaptic plasticity allows brains to learn, adapt, and rewire. It’s foundational to memory, problem-solving, and complex behavior. Those same pathways stayed quieter in mice colonized with microbes from smaller-brained primates.

Then came the surprise.

“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 Gut-Brain Axis, Made Real

Scientists have talked for years about the gut-brain axis — a two-way communication system linking digestion, immunity, mood, and cognition.

Some of that signaling travels along the vagus nerve, a thick cable connecting the gut to the brain. Some signals travel through immune molecules called cytokines. And some involve neurotransmitters that bacteria can influence — or even produce themselves.

Until now, much of this work relied on correlations.

People with certain gut microbes showed different moods, behaviors, or risks for neurological conditions. But correlation leaves room for doubt.

This study offers some much-needed clarity. It shows that microbes alone can drive changes in brain gene expression.

A Surprising Link to Mental Health Conditions

One result startled the researchers. Mice that received microbes from smaller-brained primates showed gene expression patterns linked to ADHD, schizophrenia, bipolar disorder, and autism.

That doesn’t mean macaque microbes “cause” these conditions. But the signal suspiciously matches earlier human studies that found altered microbiomes in people with neurodevelopmental differences.

“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.

She went further.

“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.”

That idea pushes the gut-brain story into uncomfortable territory. It suggests that brain development may depend, in part, on microbial timing and composition early in life.

Evolution Written in Bacteria

From an evolutionary perspective, the findings are provocative. They suggest that natural selection didn’t just shape primate brains directly. It may have shaped microbial communities that support those brains.

Large brains need energy. Microbes help extract it. Large brains need plasticity? No problem, microbes appear to tune the genes that enable it.

Amato sees this as a new way to study both evolution and development.

“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.”

The work also reframes a familiar question. Instead of asking only how brains evolved, scientists may need to ask how ecosystems — inside bodies — co-evolved with them.

The new findings were reported in the Proceedings of the National Academy of Sciences.