Brain Evolution Breakthrough: How Gut Microbiome Influenced Human Brain Size

Our brains are powerhouses, but they’re also energy hogs. As our ancestors evolved larger brains, they faced a major challenge: how to fuel this growth spurt? A new Northwestern University study reveals that our gut microbes may have been key players in solving this evolutionary puzzle.

The study offers a new perspective on human evolution, particularly the evolution of our large brains.

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In a controlled lab experiment, researchers implanted microbes from two large-brain primate species (human and squirrel monkey), and one small-brain primate species (macaque), into mice. Their findings showed the mice with microbes from large-brain primate species produced and used more energy, while those with microbes from the small-brain species stored more energy as fat.

“We know the community of microbes living in the large intestine can produce compounds that affect aspects of human biology — for example, causing changes to metabolism that can lead to insulin resistance and weight gain,” said the study’s first author Katherine Amato, associate professor of anthropology at Northwestern.

“Variation in the gut microbiota is an unexplored mechanism in which primate metabolism could facilitate different brain-energetic requirements,” Amato said.

Prior investigations have examined the genetic and environmental determinants of brain size variation across primate species. Nevertheless, there is a paucity of research directly comparing energy utilization patterns among these species. Furthermore, the developmental trajectories of metabolism in different primate lineages remain largely unexplored.

After introducing the gut microbes into microbe-free mice, the researchers measured changes in mouse physiology over time, including weight gain, fat percentage, fasting glucose, liver function and other traits. They also measured differences in the types of microbes and the compounds they were producing in each group of mice.

The researchers expected to find microbes from different primates would lead to differences in the biology of the mice inoculated with them. They also expected mice with human microbes to have the greatest difference in biology from mice with microbes from the other two species.

“While we did see that human-inoculated mice had some differences, the strongest pattern was the difference between large-brained primates (humans and squirrel monkeys) and smaller-brained primates (macaques),” Amato said.