Your stomach bacteria is changing the way you think.

Moral enhancements and your micriobiome.

Why the saying “thinking with your gut” is more accurate than you probably realize.

By Daniel Sprockett
Illustration by Daniel Gray

This is part four of a four part on series on the significant but largely unknown impact that microbes have on our lives. Read the rest here.

Imagine a world that is plagued with dire problems that require complex, abstract solutions and long-term cooperation between nations with competing interests. Now imagine that world is inhabited by a species of ape that has lived almost exclusively in small hunter-gatherer communities that rarely come interact with one another. This is the picture of the world painted by biomedical ethicist Julian Savulescu, the Uehiro Chair in Practical Ethics at the University of Oxford. This is our world.

Our brains, and therefore our behaviors, are largely a result of natural selection that occurred over the last 200,000 years. Our Pleistocene-era evolutionary history has left us ill equipped to deal with the most pressing issues of modern life, including global climate change, infectious diseases, terrorism, and rampant poverty. As a result, our moral intuitions and behaviors are poorly adapted to the highly industrialized and globalized societies that we find ourselves in today.

For example, we exhibit a limited form of altruism that is normally restricted to our close friends and family. This sociologically myopic bias towards the near future and immediate environment results in cooperative impulses that are severely constrained by group size.

However, recent advances in cognitive neuroscience have shown that many behaviours that are normally associated with morality are also highly mutable. For example, you can increase generosity, trust, and cooperation by simply instructing subjects to take a whiff of the hormone oxytocin. Prozac, a medication that regulates the neurotransmitter serotonin, is commonly prescribed for depression, but it also decreases aggression. Since these types of pro-social behaviors are necessary to address global issues like climate change and terrorism, Savulescu argues that we should be using these behavior-modifying neurochemicals to achieve more ethically desirable outcomes.

In some circles, discussions concerning the physical basis of thought always seem to lead to proclamations of a vague sort of ghost-in-the-machine-style mind/body dualism. While I don’t wish to start an argument about the primacy of free will, I will point out that our brains, and as our thoughts and behaviors, are already being influenced by the few pounds of microbes that live in our gut.

The fusion of neuroscience and microbiology has revealed the profound effects that your microbiome has on your behavior, influencing everything from the way you handle stress to to your ability to learn and remember new information. Investigating how your 86 billion neurons interact with the 100 trillion indigenous microbes is probably one of the most complex and ambitious questions scientists have ever asked. However, some key experiments have begun shedding light into that black box.

Cartoon by Ben Juers

Scientists routinely use behavioral tests and germ-free mice to study how microbes impact anxiety and emotional responsiveness. For example, the light/dark test involves placing a mouse into a chamber that is one third-dark, and two-thirds brightly illuminated. By measuring how much time it spends in each area, they can reliably quantify how curious or anxious the mouse is. Germ-free mice spend significantly more time in the well-lit areas of the cage than genetically identical mice that have been colonized normally by microbes, indicating that the microbes may be increasing the fear response in mice. Even more compelling, when you then colonize the mice with a normal microbiota, the difference disappears completely.

Of course, different types of mice have different baseline levels of curiosity. For example, the BALB/c strain of lab mice is known for being quite timid, while the NIH Swiss strain of mice is comparatively more inquisitive. When you subject these two groups of mice to a simple step-down behavioral test, where you measure how long it takes mice to step down from an elevated platform, you normally find that the timid BALB/c mice stay on the platform nearly 14 times as long as the NIH Swiss mice. If you colonize germ-free BALB/c mice with microbes from the bold and inquisitive NIH Swiss mice, they become far more interested in exploring the cage and step off of the platform significantly sooner. When the inverse is done, and germ-free NIH Swiss mice are colonized with BALB/c microbes, they take nearly three times as long to step off of their platform. Just like obesity can be transferred by microbes, so can behavioral traits.

How are microbes able to wield this kind of influence? Researchers haven’t yet identified the mechanism, but as a professor in my department is fond of saying, our gut microbiome is essentially an unsupervised chemical factory, churning out all sorts of bioactive molecules capable of interacting with hundreds of different body systems, including your nervous system. In fact, your gut houses more than 100 million neurons, which are collectively known as the enteric nervous system. Common microbes in your gut are capable of secreting a wide range of neurotransmitters that influence the intestinal branch of your nervous system. Serotonin, which is involved in mood and sleep regulation, is mainly produced by cells in the gut, but can also be synthesized by common gut microbes in the groups Escherichia, Streptococcus, and Enterococcus, as well as some Candida species of yeast. Dopamine, which is important in the reward centers of our brain, can be produced by several bacterial species, including S. aureus, B. subtilis, and E. coli. Both serotonin and dopamine act in the prefrontal cortex, a region of the brain that has been implicated in the development of moral reasoning.

Furthermore, anxiety and depression have been associated with abnormal gamma-aminobutyric acid (GABA) signaling, as well as commonly occurring with several types of bowel disorders. Interestingly, treatment with the bacteria Lactobacillus rhamnosus was shown to not only increase GABA receptor expression in the brain, but also reduce anxiety and depression in mice.

Interestingly, these researchers found that these beneficial effects could be completely removed by severing the vagus nerve that runs from the gut to the brain. This showed that L. rhamnosus affects the brain and behavior through interactions with the gut-brain axis. This bi-directional network of nerves running between the gut and the brain both sends and receives messages. Researchers now argue that since microbes exert so much influence over digestion, mood, and behavior, this concept should be extended to the microbiome-gut-brain axis.

So are we really just human marionettes, puppeted by 100 trillion microbial strings?

Well…maybe. But think of it this way: if microbes are tugging strings that affect our health and physiology, then maybe we can pull on strings that control the microbes, too. Microbes that tweak the time it takes a mouse to step off a platform is a large leap from microbes that alter our moral decision-making. However, the tools needed to engineer bacterial cells, or even whole microbial communities, are being developed now. It will take decades more research, and may ultimately not be even possible. However, the growing body of evidence shows that wide swaths of human behavior are at least in part influenced by our microbial partners. Our mind — from our social interactions to the way we perceive our environment — is an emergent collaboration between the billions of neurons in our guts and brain, and the trillion microbes that call our body home. When society decides to develop the programs for moral enhancement that Julian Savulescu has in mind, our microbiome is a prime place start.

Daniel Sprockett is a PhD student in the Department of Microbiology and Immunology in the Stanford University School of Medicine in Palo Alto, California, where he studies the ecology of the human microbiome.

Twitter: @DanielSprockett

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