Guest post by Andrew Neff

Walking into a recent psychiatry Grand Rounds meeting, I found on the projection screen a picture of a person with intestines where their brain should be. Some time before, I watched a YouTube video in which gut bacteria are said to be dictating human behavior – the Gepetto to our Pinocchio. Again, this time in the pages of The Psychologist, I discovered more puppet-based metaphors, more assertions of gut bacterial control over the human mind.

The claim that human psychological variability is driven by gut microbes is provocative. If it’s true, we’re living in a biologically deterministic world, with little room for everyday psychological explanations. The nature of our upbringing, our socioeconomic environment, the quality of our relationships, our Twitter follower count — the more influential gut microbes are, the less important traditional explanations can be.

My wife is a social worker, which means that over dinner we often discuss her troubled clientele. As a kid, one client witnessed their dad physically assault their mom. After years of bad grades and disruptive classroom behavior, the client was expelled from high school. At 18, this person is imagining a future with little-to-no job prospects, no real family support, and potentially even homelessness. To suggest that this client’s anxiety over his future can be explained by which bacteria are in his gut, rather than his fear of living through a Michigan winter on the streets, would not contribute to dinner table harmony.

To be sure, it’s possible that behaviorists are seeing patterns where there aren’t any. Maybe this client’s abusive father, absent mother, and general failure to get by in society isn’t the real explanation for his psychological turmoil. But, maybe people really are comprehensible in the context of their experiences.

Research turns to sh*t

As a graduate student I came to the so-called gut-brain axis, the idea that gut microbes are influencing psychology, by accident. Studying microbes offered me a way to remain in neuroscience while still learning how to use the incredibly interesting new tools of molecular biology. My mentor always had a balanced perspective on the role of microbes in psychology, as did most scientists, so I went along with it.

This balanced perspective, however, was not shared by everyone. An affirmative tweet under #gutbrain or a casually accepting comment from a friend could be forgiven. Slightly more troubling was the endorsement by the popular media, where attitudes ranged from accepting to outright enthusiastic. More scientists were coming to believe in the promise of gut bacterial diagnostics and therapeutics, as researchers from my institution began probing my thoughts on how the gut microbiome relates to their mental illness of interest. Couldn’t we take a step back and ask whether bacteria were doing anything in the first place?

But the field was taking off, over the five years I spent in graduate school, the number of neuroscience or psychology papers referencing gut bacteria doubled, and the National Institute of Health is now spending some thirty million dollars annually on this type of research. National conferences in psychiatry were holding special workshops on the idea, in which generally skeptical scientists presented data that seemed to support an attitude of credulity. And then there was one scientist, probably the most highly cited and visible in the field, who was giving talks and writing about how we’re not so unlike Pinocchio, passively responsive to our gut microbial puppet-masters.

For over 150 years we’ve been trying to treat mental illness from a biological perspective; EEG, fMRI, blood-based biomarkers – almost none of it is making an impact on people’s lives, but we’re confident the answers we’ve been waiting for are in our stool?

Whatever your intuition is, we could just test the idea, and to some extent, we have. If we manipulate our gut microbiomes, can we produce results that look like a human response to trauma? Can microbial alterations trigger prolonged periods of depression or anxiety?

(Limited) Evidence for the gut-brain axis

The first piece of evidence for the idea that microbes influence our behavior came from researchers who were growing mice in completely germ-free conditions.  To their surprise, these mice had a more intense response to stress than did the normal animals (1).  But when asking about what makes people different, or what makes people change over time, we’re talking about variability. Research on germ-free animals doesn’t really tell us about the psychological questions that we really care about.

To address the question of variability, we can try to ask how individual bacterial species are impacting us. We do this with what are called probiotics. These are the bacteria you find in natural foods like yogurt or kimchi or in raw pill form in the health supplement aisle. Though controversial, some compelling research supports the idea that certain bacteria are good for your emotional health (2).  And many of the probiotics we take are based off species that naturally live in the gut.  However, it’s unclear how similar the two species are.

For one, probiotics tend to be generic, one-size-fits-all species.  In contrast, the bacteria you find in your gut are highly individualized, often genetically different than the ones we take as probiotics. Second, many of the probiotics we take don’t make it through the stomach alive, while those that do typically fail to establish a long-term presence, like natural residents do (3). What all this means is that probiotics can tell you more about what probiotics do to people, but less about what’s naturally happening in your body. 

Now the gold-standard type of experiment, that lets us look at what makes us different, and is thought to be really representative of our natural gut environment, is the fecal transplant. In one study, researchers started with two strains of mice: one tended to be adventurous, the other timid.  They then had those strains swap stools, and incredibly, each strain of mouse started acting a little bit more like the other (4).  But, we have a long way to go, because humans are not mice, and emotion is complicated. As of writing this article, there is no published evidence using a placebo control in humans showing that fecal transplants can elicit the psychological characteristics of their donors.

So, what?

When I began looking into the research, I was certain there would be no convincing evidence that bacteria are impacting the brain and behavior. Humans were just too complex and variable, and most importantly, when scrutinized enough, comprehensible in psychological terms. But it’s clear that sometimes biological factors can have a major impact on our minds. In many cases, things like genetics, or the use of psychiatric meds can have subtle effects on general psychological domains, slightly boosting or dampening the likelihood of one outcome or another. The prevailing attitude, even among the more outspoken proponents of the theory that gut microbes are influencing psychology, is that if gut microbes are playing a role, they are one influence among many, subtly coloring the way in which we perceive and interact with our world. That is, IF they’re playing any role at all.

Maybe one day we’ll be able to replace Cognitive Behavioral Therapy and Mindfulness Meditation with a spoonful of yogurt and a bowl of fermented cabbage. Or maybe we’ll have a clinical rationale for requesting a stool from our most psychologically-balanced friends. But maybe we won’t. In a world where almost everyone is impacted by mental illness, either suffering themselves or knowing someone who does, it’s understandable that we’re hungry for solutions. But until we see the results from well-controlled human experiments (and independent replications), we might need to accept that we don’t know.

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Andrew completed his PhD in Neuroscience at Wayne State University, studying how the gut and brain interact. He currently teaches psychology at Rochester University and is the founding editor of Neuroscience From Underground. Follow the blog on Twitter @neuroscience_fu and Instagram @neurosciencefromunderground

A version of this post appeared on Neuroscience From Underground.

References

(1) Sudo, Nobuyuki, et al. “Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice.” The Journal of physiology 558.1 (2004): 263-275.

(2) McKean, Jennifer, et al. “Probiotics and subclinical psychological symptoms in healthy participants: a systematic review and meta-analysis.” The Journal of Alternative and Complementary Medicine 23.4 (2017): 249-258.

(3) Elli, Marina, et al. “Survival of yogurt bacteria in the human gut.” Appl. Environ. Microbiol. 72.7 (2006): 5113-5117.

(4) Bercik, Premysl, et al. “The intestinal microbiota affect central levels of brain-derived neurotrophic factor and behavior in mice.” Gastroenterology 141.2 (2011): 599-609.

Additional References (not cited in text)

Cryan, John F., and Timothy G. Dinan. “Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour.” Nature reviews neuroscience 13.10 (2012): 701.

Kang, Dae-Wook, et al. “Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.” Microbiome 5.1 (2017): 10.

Kelly, John R., et al. “Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat.” Journal of psychiatric research 82 (2016): 109-118.

Kuleshov, Volodymyr, et al. “Synthetic long-read sequencing reveals intraspecies diversity in the human microbiome.” Nature biotechnology 34.1 (2016): 64.

McKean, Jennifer, et al. “Probiotics and subclinical psychological symptoms in healthy participants: a systematic review and meta-analysis.” The Journal of Alternative and Complementary Medicine 23.4 (2017): 249-258.

Metges, Cornelia C. “Contribution of microbial amino acids to amino acid homeostasis of the host.” The Journal of nutrition

Zheng, P., et al. “Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism.” Molecular psychiatry 21.6 (2016): 786.