How did human brains get so big? The answer could be in our gut.

03 December 2024

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Microbes supporting the production of more metabolic energy could be key to the evolution of large brains.
 

  • New research provides the first evidence that differences in gut microbiomes across species are linked to how energy is used in the body. This could have shaped human evolution of larger brains.
  • The gut microbiome is a community of microorganisms in the digestive system. Previous research has linked changes in the gut microbiome to changes in host metabolism (the processes in the body that convert or use energy).
  • The study found that mice given gut microbes taken from large-brained primates ate more and shifted their energy usage to glucose – the brain’s primary fuel source. Whereas the mice that were given gut microbes from smaller-brained primates stored the energy as fat.
  • This change in energy utilization could be an explanation of how humans were able to evolve large brains relative to body size that are energetically expensive to maintain.

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 on Dec. 3. 

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 paper ‘The primate gut microbiota contributes to interspecific differences in host metabolism' by Elizabeth K. Mallott, Sahana Kuthyar, Won Lee, Derek Reiman, Hongmei Jiang, Sriram Chitta, E. Alexandria Waters, Brian T. Layden, Ronen Sumagin, Laura D. Manzanares, Guan-Yu Yang, Maria Luisa Savo Sardaro, Stanton Gray, Lawrence E. Williams, Yang Dai, James P. Curley, Chad R. Haney, Emma R. Liechty, Christopher W. Kuzawa and Katherine R. Amato, will be published in Microbial Genomics on the 3rd December 2024.

DOI: 10.1099/mgen.0.001322

URL: https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.001322 

For more information regarding the paper or to obtain a copy of the manuscript ahead of the lifting of the embargo please contact [email protected].

Image: Annelise Capossela 

About the Microbiology Society

The Microbiology Society is a membership charity for scientists interested in microbes, their effects and their practical uses. It has a worldwide membership based in universities, industry, hospitals, research institutes, schools, and other organisations. Find out more at microbiologysociety.org.

For further information please contact [email protected]

 

About the Microbiology Society

The Microbiology Society is a membership charity for scientists interested in microbes, their effects and their practical uses. It has a worldwide membership based in universities, industry, hospitals, research institutes, schools and other organizations. It also publishes the peer-reviewed journal Microbial Genomics. Find out more at microbiologysociety.org.

For further information please contact [email protected].


Image: Annelise Capossela .