Right on the top of your shoulders and neck, at your very highest point, stored safely away in the case of your skull, sits your brain (your head-brain, to be quite precise). Up there in your head the brain performs incredible feats, like calculating large sums, getting you from your bed to your desk (through peak hour traffic) dreary eyed and half asleep, reminding you when to feed your dog and take your medicine, reading Shakespeare, and navigating the complex social world. Not surprisingly, we humans consider the brain to be a very precious organ, investing much time and money trying to understand it and protect it from harm. We have constructed big, expensive magnets to peek inside our skull and see the brain at work (MRI). We wear unfashionable hardware to protect it from injury, and we keep it far away from danger by storing it at the highest point on our body. These protective behaviors are well founded – our brain is a phenomenal and delicate machine, housing around 86 billion neurons, and 100 trillion synapses (connections between neurons). These connections converge together to form hundreds of brain regions, which then speak to one another in a seemingly endless number of patterns. What’s more, each of us has a unique brain version, shaped and moulded by our own distinct life experiences. The structure, functions, and computing power of the brain is quite literally mind-boggling.
As a species, we are therefore extremely proud of the brain in our head, and rightly so. But this head-brain is not alone in its brilliance. Somewhere else, lurking in the depths of our body, is another brain, in many ways as complex and important as the one you already know so well. This second brain actually does exist, and it comes in the most unusual form. It is our gut (or, more precisely, our gastrointestinal system). Surprised? I was too.
Our second brain, much like our first, is a complicated structure, involving an entire nervous system – the enteric nervous system (ENS). The ENS is comprised of around 500 million neurons (about the amount in our spinal cord) and is capable of operating independently of our head-brain (or central nervous system; CNS) as well as interacting with it, via the vagus nerve. These brain-gut interactions are important for feeding and digestion, with the head-brain sending information to the gut-brain about the availability of food (“I see cupcakes”), and the gut-brain relaying important sensory signals back up to the head-brain (“mmm… feed me cupcakes”). Given the complexities of our two brains, however, it is perhaps not surprising that they are involved in much more than the business of digestion. In fact, brain-gut interactions are now known to be critically involved in the regulation of our thoughts and feelings, and are the new frontier in mental illness research and treatment. Anxiety, depression, and gastrointestinal problems often go hand-in-hand. For example, individuals with functional gastrointestinal disorders (such as irritable bowel syndrome) experience anxiety at a much higher rate than the general population. Treating the gastrointestinal system can help emotional symptoms. Further examples can be found in the fact that, stimulating the vagus nerve has been shown to decrease depressive symptoms in chronically depressed patients, and antidepressants that target serotonin (e.g., Prozac) can cause gastrointestinal upset. Incredibly, over 95% of this important mood-related neurotransmitter is actually produced in the gut.
Michael Gershon of Columbia University (and author of ‘The Second Brain’ – the naming inspiration for this blog) is one of the founders of the field of brain-gut interactions or ‘neurogastroenterology’, and has dedicated much of his career to studying gut disorders that are related to emotional health (e.g., gastroenteritis and IBS). More recently, psychologists and psychiatrists have begun to pay attention to the gut when investigating the mind, extending the field into the realm of ‘psychoneurogastroenterology’. And things get even more complex. With recent advances in gene sequencing technology, scientists have extended their analysis of the brain-gut axis to include the microbiome – the community of bacteria living in the gastrointestinal system. In the not so distant past, microbiologists were restricted to researching the few bacteria that would grow on a plate. Now however, scientists can sequence microbial genes from any site of the body to find out who is living there. To understand the community of bacteria living in the gut, researchers usually study human stool (poop). This is where things get really interesting, because while the CNS and the ENS are incredibly complex, the gastrointestinal microbiome is, quite literally, another world.
While we consider ourselves to be human, by most recent estimates we are actually made up of a little less than 50% human cells (depending on the last time you went to the bathroom). The rest of the cells in our body are bacteria, fungi, and Archaea (and viruses too; although, strictly speaking, viruses aren’t actually cells). In our gastrointestinal system alone we have about 3 pounds of microbes and this teeming mass of non-human life is critical for many of our human functions. For example, our earliest microbes are essential for whipping our immune system into shape, protecting us across our lifespan. When not enough of the right bacteria are present early in life, it can upset our immune responses, contributing to immune-related disease, e.g., asthma. Importantly, immune functioning is also closely related to our mental health. Inflammation is higher in chronically depressed individuals, and depressive symptoms (e.g., lethargy, irritability, decreased appetite) are also characteristic sickness behaviors in individuals with increased inflammatory pathway activity.
Rodent studies have shown that growing up germ-free (i.e., with no microbiome at all) leads to some strange effects in the brain and behavior. For example, adult activity in the amygdala (a small almond-shaped region involved in emotion, cognition, and attention) is programmed by our early exposure to bacteria. No bacteria leads to excess amygdala activity and high anxiety (in other words, these germs are actually beneficial to our mental health). Importantly, many of the changes that occur following a germ-free childhood are not reversible, even after introduction of bacteria, suggesting that our early microbiome can set-the-stage for emotionality across the lifespan.
While it might be scary to think of the influence our gut has on the brain and mental health, such fears should be reduced when we consider the many new avenues for prevention and treatment of anxiety, depression, and numerous other psychopathologies that this field opens up. Rodent studies have shown great promise of prebiotic and probiotic therapies in treating anxious and depressive behaviour, and some human studies seem to support that interpretation. Taking it one step further, we can replace the entire community of microbes in the gut (via fecal transplant – yes, this is actually happening in the world!), which is considered curative for life-threatening clostridium difficile infections. Such microbiome transplants are also effective in changing anxiety behaviour (and even obesity!) in rodents. Creating nutritional interventions that aim to cultivate a ‘healthy’ microbiome may also be in the future of mental health treatment. Even applying old treatments in new ways (e.g., anti-inflammatory treatments for depression) is an exciting step forward.
This field is young but is moving fast, so staying up to date with the latest information is imperative. In this blog I will be providing my own synopsis of interesting studies and ideas in the field of brain-gut-microbiome science, giving you the most up-to-date information from across the globe. I will also be highlighting the research programs of scientists on the front-line, exploring these issues in labs around the world. Finally, I aim to share with you all of the other great resources I have been exposed to by doing regular book reviews and scientific paper updates. So, my fellow gut lovers, read, follow, comment, share, and enjoy!