The Second Brain: the science of the gut continues to make good on its promise to aid in the understanding and treatment of mental disorders and beyond

Although philosophers and scientists have mused over the relationship between mind and body for millennia, modern research on the workings and dysfunctions of the mind has tended to focus on the central nervous system (CNS), composed of the brain and the spinal cord. If something is going wrong with behavior or thought, it follows that the problem likely stems from some anomaly in the CNS, which itself drives behavior and thought. Autism, depression, and anxiety disorder are but three of hundreds of poorly-understood conditions that have been predominantly studied through the lens of the CNS, to nearly no avail. But a growing minority of researchers and medical practitioners is finally making serious headway into developing treatments for some of these maladies, by zooming out from an exclusive focus on the CNS, and shifting the spotlight to the lesser-appreciated, so-called ‘second brain’: the gut.

The brain communicates with the gut via the enteric nervous system.

The brain communicates with the gut via the enteric nervous system.

At first glance, the gut, which is regulated by a large collection of neurons known as the enteric nervous system, has little to do with one’s mental state. Sure, your appetite reflects some interplay between your conscious tasty wants and your subconscious nutritional needs, but beyond digestion, why would the state of the stomach affect the state of the mind? Give it a few more seconds to sink in. Shouldn’t take long. I know I’m not the only person who gets moody and distractible when he’s underfed. Put my digestive system into a state of panic, and you might as well have set off a figurative fire alarm in my brain.

Psychiatrists themselves have long noticed that their patients often suffer from gastrointestinal problems. With the advent of biological psychiatry in the mid-20th century, however, psychiatrists overwhelmingly turned to psychiatric drugs to treat their patients. Yet none of these drugs proved to be a panacea for their intended conditions, and the need for reliable psychiatric treatments has remained, if not grown. Millions of psychiatric patients continue to under- and over-eat, or spend days constipated or on the verge of diarrhea or vomit, to say the least of what might happen if your gut were to malfunction. Moreover, the enteric nervous system contains more neurons than your spinal cord, and produces 95% of the serotonin, and 50% of the dopamine, found in your body. Both serotonin and dopamine are neurotransmitters better known for their roles in the brain, and for their associations with mental illness – perhaps the presence of neurotransmitters in both the brain and the gut is more than coincidence, just like the comorbidity of mental illness with GI dysfunction.

Fecal bacteria (E. coli) at 10,000x. (Wikipedia)

Fecal bacteria (E. coli) at 10,000x. (Wikipedia)

Enter the microbiome of the gut, the diverse population of trillions of tiny bacteria living in your stomach and intestine. In the last decade, doctors worldwide have had remarkable success with treating gastrointestinal (GI) disorders by attempting to normalize the populations of bacteria living in the gut. Bacterial cells outnumber human cells in each and every one of us by ten to one, and importantly, people with GI problems often have an imbalance in what types of bacteria are present in their guts, and in which proportions. In the early 2000s, well before the FDA had even approved it, GI doctors nationwide began performing what is called a ‘fecal microbiota transplant’ (FMT) – that is, transplanting the bacteria-rich stool of a healthy person into the gut of an unhealthy person. While this might strike you as disgusting, or unhygienic, employing a medical treatment based on stool is nothing new. Doctors in medieval times even used to taste the stool of their patients in order to make a diagnosis! These modern FMTs were wildly successful, so much so that the FDA fast-tracked approval of the technique this year. But moreover, with a transitive connection now existing between gut microbia, the health of the gut, and the health of the mind, a number of relatively simple experiments seemed too obvious to avoid. What if depression wasn’t causing GI malaise, but rather, GI malaise was causing depression? Could one infer that proper mental health depended on proper GI health, and therefore a healthy balance of gut bacteria?

Scientists recently succeeded in treating a mouse model of autism by altering the gut microbia balance, through oral introduction of a single bacterium found in the human colon, Bacteroides fragilis.

Scientists recently succeeded in treating a mouse model of autism by altering the gut microbia balance, through oral introduction of a single bacterium found in the human colon, Bacteroides fragilis.

The steady trickle of anecdotes suggesting this transitive relationship have recently accelerated into a remarkable stream of findings confirming that, indeed, a healthy gut encourages, and perhaps directly maintains, a healthy mind. Building off of basic findings such as this one, which found that specific gut microbia are necessary for stress regulation in rodents, researchers recently succeeded in altering the behavior of anxious mice by replacing their gut microbiota with the gut microbiota of calm mice. Other scientists showed that the behavioral traits of pregnant mice were passed down to their offspring through transmission of their particular milieu of vaginal bacteria into their newborns’ guts. Another recent study succeeded in ameliorating the symptoms of mice bred to display an autism-like phenotype by feeding them a bacterium found in the human gut (a probiotic treatment), which also restored the normal balance of gut microbia and alleviated the GI problems of these mice. None of this is extremely surprising – after all, some psychiatrists have had great success helping autistic children by directly treating their GI disorders. Nevertheless, these new findings are very encouraging for a field that is only now blossoming after decades of stagnation.


I’ve only cited the tip of the iceberg with regard to the gut microbiome and human mental health – and human health in general. A recent piece in the Atlantic enthusiastically described a hypothetical scenario in which expensive, healthy stool is sold in an upscale, pharmacy-esque setting, suggesting that the future of health care itself may come to depend on restoring the balance of gut microbia in patients with a variety of ailments, using FMT. A balanced gut microbiome appears to be important for maintaining a healthy body weight in both humans and rodents. Doctors have compelling cases to make for gut health influencing skin health, and for the abnormal release of gut microbia into the bloodstream leading to depression. We still have much work to do if we want to understand just how gut bacteria interact with the brain, perhaps via the enteric nervous system, in order to influence behavior and emotion, and the health of other organs. Unlike treatments that depend on discovering a single factor that will cure a condition, procedures such as FMT depend more on the diversified microbiome of a healthy gut. Such a treatment is also relatively cheap. It may be hard for pharmaceutical companies to profit off the transplantation of stool between people, but the proof (for patients) is in the… er… FMT. It is high time we considered the connection between mind and body as more than a ‘problem’, but as the target for valuable solutions to many of the woes of the human mind.

Leave a Reply


  1. Jill Nelson

    So, what can we do to improve our gut health? Suggestions on probiotics that are most effective? Thank you for the interesting article!

    • GMAN

      Kefir (miracle drink, I’d recommend this to EVERYONE), yogurt, sauerkraut, kimchi, kombucha.
      Stick with food, pills can’t compare.

  2. Levi Gadye

    Thanks for your comment, Jill! I think this is a good opportunity to clarify some of the nuances of these ideas.

    In retrospect, I regret using the term ‘probiotic’. Yogurt and kombucha aren’t going to cure the vast majority of people who need help with their guts, and frankly, a lot of money is currently riding on the term ‘probiotic,’ but very little believable science. My article was not intended to encourage people to change their diets, eat probiotics, or trade stool. In fact, I would strongly discourage these things.

    Truth is, we do not know (just yet) how to manipulate gut bacteria for most people out there. FMT was recently approved for symptoms that occur when patients experience an over-abundance of a particular bacterium, C. difficile, following strong antibiotic treatment. FMT may have promise with treating Crohn’s disease, and who knows, maybe even mental illness in the future, but remember, promise is very different from proven utility. Until we know more about how gut microbiota can be manipulated in humans, any application of FMT beyond C difficile will be experimental, and not guaranteed.

    In summary: science is now validating (numerous) anecdotal observations that there may be links between gut bacteria, the enteric nervous system, and the brain. It’s up to future research and future clinical trials to define useful treatments for humans. Until then, stay tuned! 🙂

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