Did Gut Microbes Help Fuel the Evolution of Large Human Brains?

The Energetic Cost of Brain Growth

The evolution of the human brain is one of the most remarkable chapters in our species' history. With its unparalleled size and complexity, the human brain consumes a disproportionate amount of energy relative to the rest of the body. Brain tissue, one of the most metabolically expensive types, requires a steady and substantial energy supply. While previous studies have explored the roles of diet, environmental pressures, and genetics in brain development, new research¹ highlights an intriguing factor: gut microbes.

Microbes and Metabolism: A Surprising Connection

A recent study published in Microbial Genomics by researchers from Northwestern University suggests that gut microbes may have played a pivotal role in supporting the metabolic demands of large-brained primates, including humans. These microscopic organisms in the digestive system not only help break down food but also influence energy production and utilization, potentially shaping evolutionary pathways.

Putative model for microbial influences on the metabolism of high-EQ and low-EQ primates. Our findings indicate microbially mediated pathways through which the metabolism of high-EQ primates is biased towards energy production and the metabolism of low-EQ primates is biased towards energy storage.

The Experiment: Mice Meet Microbes

Primates and Their Gut Communities

To investigate the role of gut microbes in brain energetics, researchers designed a controlled lab experiment. They transplanted gut microbes from three primate species into germ-free mice:

• Humans (Homo sapiens), representing a large-brain species.

• Squirrel monkeys (Saimiri sciureus), another large-brain species.

• Macaques (Macaca mulatta), a small-brain species.

Tracking Biological Changes

After inoculating the mice with the microbes, researchers monitored physiological changes over time, including weight gain, fat percentage, fasting glucose levels, and liver function. They also examined the types of microbial compounds produced in each group.

"We know the community of microbes living in the large intestine can produce compounds that affect aspects of human biology," explained Katherine Amato, associate professor of anthropology at Northwestern and lead author of the study. "For example, these compounds can cause changes to metabolism that lead to insulin resistance and weight gain."

Key Findings: Microbes of Large-Brain Primates Drive Higher Energy Use

Energy Production vs. Fat Storage

The results revealed a striking pattern: mice inoculated with gut microbes from large-brain primates (humans and squirrel monkeys) produced and utilized more energy compared to those inoculated with microbes from small-brain primates (macaques). The latter group stored more energy as fat.

"While we did see that human-inoculated mice had some differences, the strongest pattern was the difference between large-brained primates and smaller-brained primates," said Amato.

Interestingly, despite humans and squirrel monkeys not being closely related evolutionarily, their gut microbes produced similar effects on the mice. This suggests that the shared trait of having large brains, rather than ancestry, shaped these microbial communities.

"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 added.

Implications for Human Evolution

Gut Microbes as Evolutionary Partners

The study highlights gut microbes as an underexplored factor in evolutionary biology. By altering how energy is produced and used in the body, these microorganisms may have facilitated the development of larger brains in primates by meeting their high metabolic demands.

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

This perspective offers a fresh lens through which to examine the interplay between biology and evolution, particularly regarding traits that demand substantial energetic investment.

Future Directions

Building on these findings, researchers aim to extend the experiment to include microbes from more primate species with varying brain sizes. They also plan to delve deeper into the specific compounds produced by the gut microbes and how these influence host traits like immune function and behavior.

A New Frontier in Evolutionary Science

This research underscores the complex and dynamic relationship between humans and the microscopic organisms that inhabit their bodies. The idea that gut microbes may have contributed to one of humanity's defining traits—a large brain—adds an exciting dimension to our understanding of evolution.

"These findings reveal how interconnected our biology is, showing that even the tiniest organisms in our gut might have played a significant role in shaping who we are as a species," Amato concluded.

Related Research

These studies enhance the understanding of how gut microbiota interact with host biology, influencing metabolism, immunity, and adaptation.

1. Clayton, J. B., Gomez, A., Amato, K. R., et al. (2018).
   The gut microbiome of nonhuman primates: lessons in ecology and evolution.
   American Journal of Primatology, 80(3), e22867.
   DOI:10.1002/ajp.22867
   Explores the ecological and evolutionary dynamics of the gut microbiome in various primate species.

2. Amato, K. R. (2016).
   Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.
   American Journal of Physical Anthropology, 159(S61), 196–215.
   DOI:10.1002/ajpa.22908
   Discusses how gut microbiota influence primate ecology and evolutionary strategies.

3. Sharma, A. K., Petrzelkova, K., Pafco, B., et al. (2020).
   Traditional human populations and nonhuman primates show parallel gut microbiome adaptations to analogous ecological conditions.
   mSystems, 5(6), e00815-20.
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   Compares human and primate gut microbiomes in shared ecological environments.

4. Grieneisen, M. L., Muehlbauer, A. L., et al. (2020).
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   Investigates the microbial influence on host gene regulation in primates.

5. Amato, K. R., Mallott, E. K., McDonald, D., et al. (2019).
   Convergence of human and Old World monkey gut microbiomes demonstrates the importance of human ecology over phylogeny.
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   DOI:10.1186/s13059-019-1807-z
   Highlights the convergence of gut microbiota in humans and primates based on ecological overlaps.

6. McKenney, E. A., Rodrigo, A., & Yoder, A. D. (2015).
   Patterns of gut bacterial colonization in three primate species.
   PLOS ONE, 10(5), e0124618.
   DOI:10.1371/journal.pone.0124618
   Analyzes bacterial colonization patterns in different primate gut ecosystems.

7. Barelli, C., Albanese, D., Pafčo, B., et al. (2021).
   Interactions between parasitic helminths and gut microbiota in wild tropical primates from intact and fragmented habitats.
   Scientific Reports, 11(1), 11645.
   DOI:10.1038/s41598-021-01145-1
   Studies the interplay between parasitic and microbial communities in primate guts.

8. Clayton, J. B., Al-Ghalith, G., Long, H. T., et al. (2018).
   Associations between nutrition, gut microbiome, and health in a novel nonhuman primate model.
   Scientific Reports, 8(1), 11391.
   DOI:10.1038/s41598-018-29277-x
   Links gut microbiota composition to diet and health in a primate model.

9. Li, X., Wang, X., Zhang, M., et al. (2022).
   The relationship between gut microbiome and bile acids in primates with diverse diets.
   Frontiers in Microbiology, 13, 899102.
   DOI:10.3389/fmicb.2022.899102
   Examines the role of bile acids and microbiota in dietary adaptation across primates.

10. Gogarten, J. F., Davies, T. J., et al. (2018).
    Factors influencing bacterial microbiome composition in a wild non-human primate community in Taï National Park, Côte d'Ivoire.
    ISME Journal, 12(10), 2559–2573.
    DOI:10.1038/s41396-018-0166-0
    Investigates microbiota composition drivers in a wild primate population.

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