I once had a patient who was confused as to why I talked about her gut while treating her mind. To her, it seemed irrelevant. “After all,” she said, “it’s not like they are actually next to each other.”
While your gut and brain are housed in different parts of your body, they maintain more than just a historical connection. They remain physically connected too.
The vagus nerve, also known as the “wanderer nerve,” originates in the brain stem and travels all the way to the gut, connecting the gut to the central nervous system. When it reaches the gut, it untangles itself to form little threads that wrap the entire gut in an unruly covering that looks like an intricately knitted sweater. Because the vagus nerve penetrates the gut wall, it plays an essential role in the digestion of food, but its key function is to ensure that nerve signals can travel back and forth between the gut and the brain, carrying vital information between them. Signals between the gut and brain travel in both directions, making the brain and gut lifelong partners. That is the basis of the gut-brain romance.
So how does your body actually transmit messages between the gut and the brain via the vagus nerve? It’s easy enough to imagine the gut and the brain “talking” to each other over some kind of biological cell phone, but that doesn’t quite do justice to the elegance and complexity of your body’s communication system.
The basis of all body communications is chemical. When you take a pill for a headache, you usually swallow it, right? It enters your mouth, then makes its way to your gut, where it is broken down. The chemicals from the pill travel from your gut to your brain through your bloodstream. And in your brain, they can decrease the inﬂammation and loosen your tense blood vessels too. When the chemicals you swallow successfully exert their effects on the brain, you feel relief from that pain.
In the same way as the chemicals in that pill, chemicals produced by the gut can also reach your brain. And chemicals produced by your brain can reach your gut. It’s a two-way street.
In the brain, these chemicals originate from the primary parts of your nervous system (with an assist from your endocrine system): the central nervous system, which comprises the brain and spinal cord; the autonomic nervous system (ANS), which comprises the sympathetic and parasympathetic systems; and the hypothalamic-pituitary-adrenal axis ( HPA- axis), which comprises the hypothalamus, pituitary gland, and adrenal gland.
The central nervous system produces chemicals such as dopamine, serotonin, and acetylcholine that are critical for regulating mood and processing thought and emotion. Serotonin, a key chemical deﬁcient in the brains of depressed and anxious people, plays a major role in regulating the gut-brain axis. Serotonin is one of the most buzzed-about brain chemicals because of its role in mood and emotion, but did you know that more than 90 percent of serotonin receptors are found in the gut? In fact, some researchers believe that the brain-serotonin deﬁcit is heavily inﬂuenced by the gut, an idea we’ll dig deeper into later on.
The autonomic nervous system (ANS) is in charge of a broad range of essential functions, most of which are involuntary: your heart keeps beating, and you keep breathing and digesting food because of your ANS. When your pupils dilate to take in more light in a dark room, that’s the ANS. Perhaps most crucially for our purposes, when your body is under duress, your ANS controls your ﬁght-or-ﬂight response, an instinctual reaction to threat that sends a cascade of hormonal and physiological responses through your body in dangerous or life-threatening situations. As we’ll see later on, the gut has a profound effect on ﬁght or ﬂight, particularly through the regulation of the hormones adrenaline and noradrenaline (also known as epinephrine and norepinephrine).
The HPA-axis is another crucial part of the body’s stress machine. It produces hormones that stimulate release of cortisol, the “stress hormone.” Cortisol amps the body up to handle stress, providing a ﬂood of extra energy to deal with difﬁcult situations. Once the threat passes, the cortisol level returns to normal. The gut also plays an important role in cortisol release and is instrumental in making sure the body responds to stress effectively.
In a healthy body, all these brain chemicals ensure that the gut and brain work smoothly together. Of course, as in all delicate systems, things can go wrong. When chemical over-or underproduction disrupts this connection, the gut-brain balance is thrown into disarray. Levels of important chemicals go out of whack. Moods are upset. Concentration is disrupted. Immunity drops. The gut’s protective barrier is compromised, and metabolites and chemicals that should be kept out of the brain reach the brain and wreak havoc.
Over and over again throughout this book, we are going to see how this chemical chaos gives rise to psychiatric symptoms, from depression and anxiety to loss of libido to devastating conditions like schizophrenia and bipolar disorder.
In order to correct those chemical imbalances and restore order to brain and body, you might assume that we would need a barrage of sophisticated, carefully engineered pharmaceuticals. And to a degree, you’d be right! Most drugs used to treat mental conditions do seek to alter these chemicals to return the brain to a healthy state —for example, you may have heard of selective serotonin reup-take inhibitors (most commonly referred to as SSRIs), which boost serotonin in order to ﬁght depression. Modern mental health medications can be a godsend to patients who struggle with a variety of disorders, and I don’t want to downplay their importance as a therapy in many circumstances. But what sometimes gets lost in discussions about mental health is a simple truth: the food you eat can have just as profound an effect on your brain as the drugs you take. How can something as basic and natural as eating be as potent as a drug that cost millions of dollars to develop and test? The ﬁrst part of the answer lies in bacteria.
WHY SMALL THINGS MATTER
Behind the scenes of the gut-brain romance is a huge collection of microorganisms that reside in the gut. We call this panoply of different bacterial species the microbiome. The gut microbiome — in both humans and other animals — is another type of romance, with both parties relying on each other for survival. Our guts provide the bacteria with a place to live and thrive, and in return they perform crucial tasks for us that our bodies can’t perform on their own.
The microbiome is made up of many different types of bacteria, with a much greater diversity of species in the gut than anywhere else in the body. Each individual gut can contain up to a thousand different species of bacteria, though most of them belong to two groups —Firmicutes and Bacteroides —which make up about 75 per-cent of the entire microbiome.
While we won’t spend too much time discussing individual species in this book, sufﬁce it to say that when it comes to bacteria, there are good guys and bad guys. The microorganisms that inhabit the gut are normally good guys, but it’s inevitable that some bad ones get mixed in. This isn’t necessarily a concern, as your body generally makes sure that the good and bad bacteria stay at the right balance. But if diet, stress, or other mental or physical problems cause changes in gut bacteria, that can cause a ripple effect that leads to many negative health effects.
The idea that the microbiome plays such an essential role in bodily function is relatively new in medicine (think about how often you’ve heard of bacteria as “germs that will make you sick” rather than as a helpful team of microorganisms that performs a vital service), particularly when it comes to bacteria’s inﬂuence on the brain. But over the years, the science has been building that gut bacteria can affect mental function.
About thirty years ago, in one of the most compelling studies that ﬁrst made us aware that changes in gut bacteria could inﬂuence mental function, researchers reported on a series of patients with a kind of delirium (called hepatic encephalopathy) due to liver failure. In hepatic encephalopathy, bacterial “bad guys” produce toxins, and the study showed that these patients stopped being delirious when antibiotics were administered by mouth. That was a clear sign that changing gut bacteria could also change mental function.
In the years since, we’ve accumulated a huge amount of knowledge about how the gut microbiome affects mental health, and we’ll unpack that knowledge throughout this book. For instance, did you know that functional bowel disorders like irritable bowel syndrome and inﬂammatory bowel disease also come with mood changes due to bacterial populations being altered?5 Or that some clinicians feel that adding a probiotic as part of a psychiatric medication treatment plan can also help to lower anxiety and depression? Or that if you transfer the gut bacteria of schizophrenic humans into the guts of lab mice, those mice also start to show symptoms of schizophrenia?
The primary reason gut bacteria have such a profound effect on mental health is that they are responsible for making many of the brain chemicals we discussed in the last section. If normal gut bacteria are not present, production of neurotransmitters such as dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA) — all critically important for the regulation of mood, memory, and attention — is impacted. As we’ll see, many psychiatric disorders are rooted in deﬁcits and imbalances of these chemicals, and many psychiatric drugs are tasked with manipulating their levels. Therefore, if your gut bacteria are intimately involved with producing these vital chemicals, it stands to reason that when your gut bacteria are altered, you risk doing damage to this complex web of body and brain function. That’s a lot of responsibility for a group of microscopic organisms!
Different collections of bacteria affect brain chemistry differently. For instance, changes in proportions and function of Escherichia, Bacillus, Lactococcus, Lactobacillus, and Streptococcus can result in changes in dopamine levels and may predispose one to Parkinson’s disease and Alzheimer’s disease. Other combinations of abnormal gut bacteria may result in abnormally high concentrations of acetylcholine, histamine, endotoxin, and cytokines, which can damage brain tissue.
In addition to regulating neurotransmitter levels, there are various other ways in which microbiota inﬂuence the gut-brain connection. They are involved in the production of other important compounds like brain-derived neurotrophic factor, which supports the survival of existing neurons and promotes new neuron growth and connections. They inﬂuence the integrity of the gut wall and the gut’s barrier function, which protect the brain and the rest of the body from substances that need to be conﬁned to the gut. Bacteria can also have an effect on inﬂammation in the brain and body, particularly inﬂuencing oxidation, a harmful process that results in cellular damage.
A TWO-WAY STREET
As I mentioned earlier, the gut-brain connection works both ways. So if gut bacteria can inﬂuence the brain, it is also true that the brain can change gut bacteria.
All it takes is two hours’ worth of psychological stress to completely change the bacteria in your gut. In other words, a tense family Christmas dinner or unusually bad trafﬁc can be enough to upset the balance of your microbiome. The theory is that the ANS and HPA-axis send signaling molecules to gut bacteria when you are stressed, changing bacterial behavior and composition. The results can be damaging. For example, one kind of bacterium changed by stress is Lactobacillus. Normally, it breaks down sugars into lactic acid, prevents harmful bacteria from lining the intestine, and protects your body against fungal infections. But when you are stressed, Lactobacillus fails on all these fronts due to how stress disrupts its functioning, leaving you exposed to harm.
The brain can also affect the physical movements of the gut (for example, how the gut contracts), and it controls the secretion of acid, bicarbonate, and mucus, all of which provide the gut’s protective lining. In some instances, the brain affects how the gut handles ﬂuid. When your brain is not functioning well — for example, when you have depression or anxiety — all these normal and protective effects on the gut are compromised. As a result, food is not properly absorbed, which in turn has a negative effect on the rest of the body since it’s not getting the nutrients it needs.
WHEN THINGS GO SOUTH
So to recap, your brain needs the proper balance of gut bacteria to make the chemicals it needs to stay stable and healthy. The gut needs your brain to be stable and healthy so that it can maintain the proper balance of gut bacteria. If that cyclical relationship is disrupted, it means trouble for both the gut and the brain. An unhealthy gut microbiome leads to an unhealthy brain, and vice versa.
A quick illustration of these issues is provided by a survey Mireia Valles-Colomer and her colleagues conducted in April 2019 of more than a thousand people, in which they correlated microbiome features with well-being and depression. They found that butyrate-producing bacteria were consistently associated with higher quality-of-life indicators. Many bacteria were also depleted in people with depression, even after correcting for the confounding effects of antidepressants. They also found that when the dopamine metabolite 3,4-dihydroxyphenylacetic acid, which helps gut bacterial growth, is high, mental health is improved. GABA production is disturbed in people with depression too.
That’s just the tip of the iceberg. In each chapter of this book, we will go into speciﬁc gut-brain disturbances that map out the relationships between the microbiome and individual disorders. In the pages to come, we will see how depression, anxiety, post- traumatic stress disorder, attention deﬁcit hyperactivity disorder, dementia, obsessive compulsive disorder, insomnia, decreased libido, schizophrenia, and bipolar disorder might all be associated with an altered microbiome. For each condition, I will walk you through where we stand with research today and give you an idea where there may be room for further study.