Summary: A new study suggests that gut microbes played a key role in the evolution of larger brains in primates by influencing energy production and usage. Researchers implanted microbes from humans, squirrel monkeys (large-brained species), and macaques (small-brained species) into mice, observing that microbes from larger-brained primates enhanced energy production, while those from smaller-brained primates favored fat storage.
The findings reveal that gut microbiota differences may have evolved to meet the higher energy demands of larger brains. This research offers a fresh perspective on human evolution, emphasizing the potential of gut microbes to shape metabolic and biological traits.
Brain tissue is among the most energetically costly in the body, and as a result, larger-brained mammals require more energy to support brain growth and maintenance. Exactly which biological changes allowed human ancestors to meet the very high needs for energy as they evolved larger brains has remained unclear.
A new Northwestern University study points to the role of gut microbes, tiny living organisms in our digestive system that help break down food and produce energy.
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.
The data is the first to show gut microbes from different animal species shape variations in biology between animal species and supports the hypothesis that gut microbes might influence evolution by changing how an animal's body works.
The study offers a new perspective on human evolution, particularly the evolution of our large brains.
The findings will be published in the journal Microbial Genomics.
Prior studies have compared the influence of genes and the environment on primates with bigger and smaller brains. However, there are very few studies comparing how different primates use energy. Even less information is available on how metabolism develops in different primate species.
"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.
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.
The mice given microbes from the humans and squirrel monkeys had similar biology, even though these two larger-brained primate species are not close evolutionary relatives of one another.
This suggests something other than shared ancestry -- likely their shared trait of large brains is driving the biological similarities seen in the mice inoculated with their microbes.
"These findings suggest that when humans and squirrel monkeys both separately evolved larger brains, their microbial communities changed in similar ways to help provide the necessary energy," Amato said.
In future studies, the researchers hope to run the experiment with microbes from additional primate species varying in brain size.
They would also like to collect more information on the types of compounds the microbes are producing and gather additional data on the biological traits of the hosts such as immune function and behavior.
The primate gut microbiota contributes to interspecific differences in host metabolism
Because large brains are energetically expensive, they are associated with metabolic traits that facilitate energy availability across vertebrates. However, the biological underpinnings driving these traits are not known.
Given its role in regulating host metabolism in disease studies, we hypothesized that the gut microbiome contributes to variation in normal cross-vertebrate species differences in metabolism, including those associated with the brain's energetic requirements.
By inoculating germ-free mice with the gut microbiota (GM) of three primate species - two with relatively larger brains and one with a smaller brain - we demonstrated that the GM of larger-brained primates shifts host metabolism towards energy use and production, while that of smaller-brained primates stimulates energy storage in adipose tissues.
Our findings establish a causal role of the GM in normal cross-host species differences in metabolism associated with relative brain size and suggest that the GM may have been an important facilitator of metabolic changes during human evolution that supported encephalization.