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Column: Gut Instinct: Your microbiome’s role in decision-making and morality

Gut Instinct: Your microbiome’s role in decision-making and morality

In his fourth installment of ‘Just 10% Human,’ Daniel Sprockett introduces us to some of the invisible internal players that affect our thinking – and yes, you guessed it: our microbiome is involved in that as well…  

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Last month, my wife and I attended a compelling talk by leading biomedical ethicist Julian Savulescu as part of the Sydney Uni’s Ideas lecture series. Professor Savulescu, the Uehiro Chair in Practical Ethics at the University of Oxford, was in town to participate in an Intelligence2 debate on the ethics of letting athletes use performance-enhancing drugs. (For those interested, he was pro-enhancement, and soundly won the debate.)

However, the talk we attended was not about athletic enhancement, but moral enhancement.  He also spoke at the 2009 Festival Of Dangerous Ideas at the Sydney Opera House on this topic, and a video is available online.

His thesis was essentially that our Pleistocene evolutionary history has left us ill equipped to deal with many of the most pressing issues of modern life, including global climate change, infectious diseases, terrorism, and rampant poverty. Our brains, and therefore our behaviors, are largely a result of natural selection that occurred over the 200,000 years that Homo sapiens lived in small hunter-gatherer communities.

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 limited altruism that is generally restricted to our close friends and family, a sociologically myopic bias towards the near future and immediate environment, and cooperative impulses that are severely constrained by group size.

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

In fact, some psychologists have already begun using such techniques on a small scale. One study showed that when couples are given oxytocin during conflict counseling, they were both more communicative and less stressed.

But could similar interventions be useful for ensuring the survival of our species? Can we really change our behaviors?

As it turns out, your microbiome is already influencing your behavior in a myriad of ways.

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, but we’ve begun designing experiments that peer into the black box. The fusion of neuroscience and microbiology has enabled scientists to begin uncovering the effect your microbiome has on your behavior, influencing a wide range of systems such as the way you deal with stress and anxiety to your ability to learn and remember new information.

Scientists routinely use behavioral tests and germ-free mice to study how microbes impact anxiety and emotional responsiveness. One simple example is the light/dark test, which involves placing a mouse in an empty chamber that is one third-dark, and two-thirds brightly illuminated, and measuring how much time it spends in each area. Mice will move between the two areas because of the conflict between a mouse’s aversion to brightly lit, exposed areas, and their innate curiosity to explore new environments.

Mice that are raised completely germ-free spend significantly more time in the well-lit areas of the cage than identical mice with normally colonized with microbes. However, this difference is erased when you allow mice that are born germ-free to be colonized by microbes from normal mice.

Different mouse strains can vary widely with regard to their baseline level of curiosity/fear, and another group of researchers capitalized on these differences to uncover a fascinating pattern. They took two strains of mice, one strain is timid (BALB/c) while the other is comparatively more inquisitive (NIH Swiss), and subjected them to the step-down behavioral test. This test simply places the mouse on a small, elevated platform, and measures how much time it takes the mouse to step down. Normally, the timid BALB/c mice take over four and a half minutes to step down and investigate their surroundings, while the inquisitive NIH Swiss mice only take about 20 seconds to begin exploring.

They then raised germ-free mice of both types, and colonized them with microbes from various donors. When they used BALB/c microbes to colonize germ-free BALB/c mice, they didn’t find any differences in their exploratory behavior. The same was true for the inquisitive NIH Swiss mice when colonized with NIH Swiss microbes. However, when they used microbes from the inquisitive NIH Swiss to colonize BALB/c mice, the previously timid mouse became far more interested in exploring its cage, and stepped off of the raised platform significantly sooner. When they did the inverse, they found that the bold NIH Swiss mouse colonized with microbes from BALB/c became much more timid, and took three times as long to step off of their platform.

This study also found that administering antibiotics had a large effect not only on the mouse’s gut microbiome, but also their behavior. Antimicrobial therapy made normal mice significantly less apprehensive, as measured by both the light/dark and the step-down tests.

How is this happening? Scientists haven’t yet identified the mechanism, but we can say that microbes are probably not colonizing your brain directly. Microbes of all types have a very difficult time crossing the blood-brain barrier. One recent study did find evidence of bacterial genes in the brain, but large amounts of live microbes aren’t typically found in healthy brain tissue. But microbes don’t need to live in your brain to impact your behavior. Your gut houses more than 100 million neurons, which are collectively known as the enteric nervous system.

Early anatomists assumed that digestion was strictly regulated by signals from the brain, but we now know that important sensory information flows in both directions between the gut and brain, known as the gut-brain axis. Several researchers now argue that because microbes exert so much influence over digestion, mood, and behavior, this concept should be extended to include the microbiome-gut-brain axis.

In addition, many of the microbes commonly found in your gut are capable of secreting a wide range of neurotransmitters. Serotonin, which is involved in mood and sleep regulation, is produced by microbial species in the genera Escherichia, Streptococcus, and Enterococcus, as well as some Candida species of yeast. Dopamine, which is important in the reward centers of our brain, can also be produced by several bacterial species, including Staphylococcus aureus, Bacillus subtilis, and Escherichia coli. Both serotonin and dopamine act in the prefrontal cortex, the region of the brain behind your forehead, which has been implicated in the development of moral reasoning.

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

Not exactly. Researchers have a long way to go before we can make the leap from microbes influencing the time it takes a mouse to step off a platform, to microbes impacting our moral decision-making.

But there is a growing body of evidence 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 not the result of some vague, ghost-in-the-machine mind/body dualism, but is instead 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 types of moral enhancement that Julian Savulescu has in mind, our microbiome is a prime place start.

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Daniel Sprockett is a researcher at the Case Western Reserve University School of Medicine in Cleveland, Ohio. He currently resides in Double Bay with his wife, Andrea, while she completes a Master’s of International Public Health at the University of Sydney. Dan will return to the United States in September, when he begins his PhD in Microbiology and Immunology at Stanford University.

@DanielSprockett
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