(Credit: Chizhevskaya Ekaterina/Shutterstock)
CHICAGO — In a fascinating discovery that bridges the microscopic and the evolutionary, researchers at Northwestern University have uncovered evidence that some of our smallest passengers – gut bacteria – may have played a role in one of humanity’s biggest developments: our large brains.
The study, published in Microbial Genomics, offers a new perspective on a long-standing evolutionary puzzle. While scientists have long known that brain tissue is among the most energetically expensive in the body, the biological mechanisms that allowed our ancestors to meet these intense energy demands have remained unclear – until now.
“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,” explains Katherine Amato, associate professor of anthropology at Northwestern University and the study’s first author, in a statement.
To investigate this connection, the research team designed an experiment using three primate species with distinct brain sizes relative to their body mass: humans and squirrel monkeys (both with relatively high encephalization quotients, or EQs) and macaques (with relatively lower EQs). Rather than studying these primates directly, they transferred gut bacteria from each species into groups of germ-free mice – laboratory mice raised in completely sterile conditions with no gut bacteria of their own.
The team collected stool samples from five adult donors of each species: humans from Evanston, Illinois with normal body mass indices and no recent antibiotic use, and primates from research facilities under similar health conditions. They used these samples to colonize the guts of thirty germ-free mice, 10 per donor species, and followed their development for 60 days.
“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),” notes Amato.
The results revealed clear metabolic differences. Mice given gut bacteria from the high-EQ primates (humans and squirrel monkeys) showed higher food consumption but lower weight gain, higher blood glucose levels, and increased liver enzyme activity related to glucose production. In contrast, mice with macaque gut bacteria stored more energy as fat despite eating less.
The researchers found that these metabolic differences were associated with varying levels of short-chain fatty acids (SCFAs) – specifically acetate, propionate, butyrate, and valerate – which are produced when gut bacteria ferment dietary fiber. Mice with gut bacteria from high-EQ primates showed higher concentrations of these compounds, which can influence metabolism through multiple pathways including appetite regulation, fat storage, and glucose production.
Notably, mice receiving human gut bacteria showed distinct patterns, including the highest glucose levels and lowest weight gain among all groups. This aligns with humans having the highest EQ among primates, though the researchers caution that more research is needed to fully understand these relationships.
What makes these findings particularly intriguing is that humans and squirrel monkeys aren’t close evolutionary relatives. “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 explains.
This research represents the first evidence that gut microbes from different animal species can shape biological variations between species. It suggests that as primates evolved larger brains, they may have also developed relationships with gut bacterial communities that helped support their increasing energy demands.
Looking ahead, the research team plans to expand their investigation to include additional primate species with varying brain sizes. They also hope to gather more detailed information about the types of compounds the microbes are producing and collect additional data on host biological traits such as immune function and behavior.
From microbe to mind, who would have thought that the path to human intelligence was paved not just with genetic mutations and natural selection, but also with the metabolic support of countless microscopic allies in our digestive tracts? Perhaps there should be a new saying: When it comes to brain evolution, it’s what’s inside (your gut) that counts.
Paper Summary
Methodology
The researchers used a germ-free mouse model to isolate the effects of gut microbes on metabolism. They collected stool samples from five adult donors of each species (humans, squirrel monkeys, and macaques), screened them for normal body mass index and no recent antibiotic use, and used these to create species-specific bacterial cocktails. They then gave these bacterial mixtures to groups of ten young, sterile mice via oral administration. Over 60 days, they tracked multiple metabolic indicators, including weight, food intake, blood chemistry, body composition (using MRI scans), and various molecular measurements of both the gut bacteria and the mice’s liver function.
Results
The study revealed clear metabolic differences between mice receiving gut bacteria from different primate species. Mice with gut bacteria from humans and squirrel monkeys showed higher food consumption but lower weight gain, higher blood glucose, increased liver enzyme activity related to glucose production, and lower body fat percentage. These mice also had higher levels of specific bacterial metabolites (SCFAs) known to influence metabolism. In contrast, mice receiving macaque gut bacteria stored more energy as fat despite eating less.
Limitations
The study has several important limitations. The human donors came from a single population with low body mass index, which might not represent global human diversity. The study used a single population of each primate species, which could limit generalizability. Additionally, the mouse model, while useful for controlling variables, may not perfectly reflect how these gut bacteria function in their native primate hosts. The energy budget constraints of mice might also have affected how they responded to human gut bacteria.
Discussion and Takeaways
This research suggests that gut bacteria may have played a crucial role in enabling the evolution of large brains in certain primate species by helping to manage the intense energy demands of cerebral tissue. The findings indicate that gut bacteria might help create species-specific metabolic patterns that either favor energy availability for the brain or energy storage in fat. This work opens new avenues for understanding both human evolution and the modern relationship between gut bacteria and metabolism.
Funding and Disclosures
The study was funded by CIFAR’s “Humans and the Microbiome” Fellowship and the Samsung Scholarship Foundation. The researchers declared no competing interests. The work involved multiple institutional animal care and use committee approvals for both the primate and mouse studies, as well as human subject approval from Northwestern University’s Institutional Review Board.