It comprises an estimated 500 million neurons – about five times as many as in the brain of a rat – and is around 9 metres long, stretching from your oesophagus to your anus. It is this brain that could be responsible for your craving under stress for crisps, chocolate and biscuits
Embedded in the wall of the gut, the enteric nervous system (ENS) has long been known to control digestion. Now it seems it also plays an important role in our physical and mental well-being. It can work both independently of and in conjunction with the brain in your head and, although you are not conscious of your gut “thinking”, the ENS helps you sense environmental threats, and then influences your response. “A lot of the information that the gut sends to the brain affects well-being, and doesn’t even come to consciousness,” says Michael Gershon at Columbia-Presbyterian Medical Center, New York.
If you look inside the human body, you can’t fail to notice the brain and its offshoots of nerve cells running along the spinal cord. The ENS, a widely distributed network of neurons spread throughout two layers of gut tissue, is far less obvious, which is why it wasn’t discovered until the mid-19th century. It is part of the autonomic nervous system, the network of peripheral nerves that control visceral functions. It is also the original nervous system, emerging in the first vertebrates over 500 million years ago and becoming more complex as vertebrates evolved – possibly even giving rise to the brain itself.
Digestion is a complicated business, so it makes sense to have a dedicated network of nerves to oversee it. As well as controlling the mechanical mixing of food in the stomach and coordinating muscle contractions to move it through the gut, the ENS also maintains the biochemical environment within different sections of the gut, keeping them at the correct pH and chemical composition needed for digestive enzymes to do their job.
But there is another reason the ENS needs so many neurons: eating is fraught with danger. Like the skin, the gut must stop potentially dangerous invaders, such as bacteria and viruses, from getting inside the body. If a pathogen should cross the gut lining, immune cells in the gut wall secrete inflammatory substances including histamine, which are detected by neurons in the ENS. The gut brain then either triggers diarrhoea or alerts the brain in the head, which may decide to initiate vomiting, or both.
You needn’t be a gastroenterologist to be aware of these gut reactions – or indeed the more subtle feelings in your stomach that accompany emotions such as excitement, fear and stress. For hundreds of years, people have believed that the gut interacts with the brain to influence health and disease. Yet this connection has only been studied over the last century. Two pioneers in this field were American physician Byron Robinson, who in 1907 published The Abdominal and Pelvic Brain, and his contemporary, British physiologist Johannis Langley, who coined the term “enteric nervous system”. Around this time, it also became clear that the ENS can act autonomously, with the discovery that if the main connection with the brain – the vagus nerve – is severed the ENS remains capable of coordinating digestion. Despite these discoveries, interest in the gut brain fell until the 1990s when the field of neurogastroenterology was born.
We now know that the ENS is not just capable of autonomy but also influences the brain. In fact, about 90 per cent of the signals passing along the vagus nerve come not from above, but from the ENS (American Journal of Physiology – Gastrointestinal and Liver Physiology, vol 283, p G1217).
THE FEEL-GOOD FACTOR
The second brain also shares many features with the first. It is made up of various types of neuron, with glial support cells. It has its own version of a blood-brain barrier to keep its physiological environment stable. And it produces a wide range of hormones and around 40 neurotransmitters of the same classes as those found in the brain. In fact, neurons in the gut are thought to generate as much dopamine as those in the head. Intriguingly, about 95 per cent of the serotonin present in the body at any time is in the ENS.
What are these neurotransmitters doing in the gut? In the brain, dopamine is a signalling molecule associated with pleasure and the reward system. It acts as a signalling molecule in the gut too, transmitting messages between neurons that coordinate the contraction of muscles in the colon, for example. Also transmitting signals in the ENS is serotonin – best known as the “feel-good” molecule involved in preventing depression and regulating sleep, appetite and body temperature. But its influence stretches far beyond that. Serotonin produced in the gut gets into the blood, where it is involved in repairing damaged cells in the liver and lungs. It is also important for normal development of the heart, as well as regulating bone density by inhibiting bone formation (Cell, vol 135, p 825).
But what about mood? Obviously the gut brain doesn’t have emotions, but can it influence those that arise in your head? The general consensus is that neurotransmitters produced in the gut cannot get into the brain – although, theoretically, they could enter small regions that lack a blood-brain barrier, including the hypothalamus. Nevertheless, nerve signals sent from the gut to the brain do appear to affect mood. Indeed, research published in 2006 indicates that stimulation of the vagus nerve can be an effective treatment for chronic depression that has failed to respond to other treatments (The British Journal of Psychiatry, vol 189, p 282).
Such gut to brain signals may also explain why fatty foods make us feel good. When ingested, fatty acids are detected by cell receptors in the lining of the gut, which send nerve signals to the brain. This may not be simply to keep it informed of what you have eaten. Brain scans of volunteers given a dose of fatty acids directly into the gut show they had a lower response to pictures and music designed to make them feel sad than those given saline. They also reported feeling only about half as sad as the other group (The Journal of Clinical Investigation, vol 121, p 3094).
There is further evidence of links between the two brains in our response to stress. The feeling of “butterflies” in your stomach is the result of blood being diverted away from it to your muscles as part of the fight or flight response instigated by the brain. However, stress also leads the gut to increase its production of ghrelin, a hormone that, as well as making you feel more hungry, reduces anxiety and depression. Ghrelin stimulates the release of dopamine in the brain both directly, by triggering neurons involved in pleasure and reward pathways, and indirectly by signals transmitted via the vagus nerve.
In our evolutionary past, the stress-busting effect of ghrelin may have been useful, as we would have needed to be calm when we ventured out in search of food, says Jeffrey Zigman at UT Southwestern Medical Center in Dallas, Texas. In 2011, his team reported that mice exposed to chronic stress sought out fatty food, but those that were genetically engineered to be unable to respond to ghrelin did not (The Journal of Clinical Investigation, vol 121, p 2684). Zigman notes that in our modern world, with freely available high-fat food, the result of chronic stress or depression can be chronically elevated ghrelin – and obesity.
Gershon suggests that strong links between our gut and our mental state evolved because a lot of information about our environment comes from our gut. “Remember the inside of your gut is really the outside of your body,” he says. So we can see danger with our eyes, hear it with our ears and detect it in our gut. Pankaj Pasricha, director of the Johns Hopkins Center for Neurogastroenterology in Baltimore, Maryland, points out that without the gut there would be no energy to sustain life. “Its vitality and healthy functioning is so critical that the brain needs to have a direct and intimate connection with the gut,” he says.
But how far can comparisons between the two brains be taken? Most researchers draw the line at memory – Gershon is not one of them. He tells the story of a US army hospital nurse who administered enemas to the paraplegic patients on his ward at 10 o’clock every morning. When he left, his replacement dropped the practice. Nevertheless, at 10 the next morning, everyone on the ward had a bowel movement. This anecdote dates from the 1960s and while Gershon admits that there have been no other reports of gut memory since, he says he remains open to the idea.
Then there’s decision-making. The concept of a “gut instinct” or “gut reaction” is well established, but in fact those fluttery sensations start with signals coming from the brain – the fight or flight response again. The resulting feeling of anxiety or excitement may affect your decision about whether to do that bungee jump or arrange a second date, but the idea that your second brain has directed the choice is not warranted. The subconscious “gut instinct” does involve the ENS but it is the brain in your head that actually perceives the threat. And as for conscious, logical reasoning, even Gershon accepts that the second brain doesn’t do that. “Religion, poetry, philosophy, politics – that’s all the business of the brain in the head,” he says.
Still, it is becoming apparent that without a healthy, well-developed ENS we face problems far wider than mere indigestion. Pasricha has found that newborn rats whose stomachs are exposed to a mild chemical irritant are more depressed and anxious than other rats, with the symptoms continuing long after the physical damage has healed. This doesn’t happen after other sorts of damage, like skin irritation, he says.
It has also emerged that various constituents of breast milk, including oxytocin, support the development of neurons in the gut (Molecular Nutrition and Food Research, vol 55, p 1592). This might explain why premature babies who are not breastfed are at higher risk of developing diarrhoea and necrotising enterocolitis, in which portions of the bowel become inflamed and die.
Serotonin is also crucial for the proper development of the ENS where, among its many roles, it acts as a growth factor. Serotonin-producing cells develop early on in the ENS, and if this development is affected, the second brain cannot form properly, as Gershon has shown in mutated mice. He believes that a gut infection or extreme stress in a child’s earliest years may have the same effect, and that later in life this could lead to irritable bowel syndrome, a condition characterised by chronic abdominal pain with frequent diarrhoea or constipation that is often accompanied by depression. The idea that irritable bowel syndrome can be caused by the degeneration of neurons in the ENS is lent weight by recent research revealing that 87 out of 100 people with the condition had antibodies in their circulation that were attacking and killing neurons in the gut (Journal of Neurogastroenterology and Motility, vol 18, p 78).
If nothing else, the discovery that problems with the ENS are implicated in all sorts of conditions means the second brain deserves a lot more recognition than it has had in the past. “Its aberrations are responsible for a lot of suffering,” says Pasricha. He believes that a better understanding of the second brain could pay huge dividends in our efforts to control all sorts of conditions, from obesity and diabetes to problems normally associated with the brain such as Alzheimer’s and Parkinson’s. Yet the number of researchers investigating the second brain remains small. “Given it’s potential, it’s astonishing how little attention has been paid to it,” says Pasricha.
MENTAL ILLNESSES OF THE GUT
A growing realisation that the nervous system in our gut is not just responsible for digestion (see main story) is partly fuelled by discoveries that this “second brain” is implicated in a wide variety of brain disorders. In Parkinson’s disease, for example, the problems with movement and muscle control are caused by a loss of dopamine-producing cells in the brain. However, Heiko Braak at the University of Frankfurt, Germany, has found that the protein clumps that do the damage, called Lewy bodies, also show up in dopamine-producing neurons in the gut. In fact, judging by the distribution of Lewy bodies in people who died of Parkinson’s, Braak thinks it actually starts in the gut, as the result of an environmental trigger such as a virus, and then spreads to the brain via the vagus nerve.
Likewise, the characteristic plaques or tangles found in the brains of people with Alzheimer’s are present in neurons in their guts too. And people with autism are prone to gastrointestinal problems, which are thought to be caused by the same genetic mutation that affects neurons in the brain.
Although we are only just beginning to understand the interactions between the two brains, already the gut offers a window into the pathology of the brain, says Pankaj Pasricha at Johns Hopkins University in Baltimore, Maryland. “We can theoretically use gut biopsies to make early diagnoses, as well as to monitor response to treatments.”
Cells in the second brain could even be used as a treatment themselves. One experimental intervention for neurodegenerative diseases involves transplanting neural stem cells into the brain to replenish lost neurons. Harvesting these cells from the brain or spinal cord is not easy, but now neural stem cells have been found in the gut of human adults (Cell Tissue Research, vol 344, p 217). These could, in theory, be harvested using a simple endoscopic gut biopsy, providing a ready source of neural stem cells. Indeed, Pasricha’s team is now planning to use them to treat diseases including Parkinson’s.
As Olympians go for the gold in Vancouver, even the steeliest are likely to experience that familiar feeling of “butterflies” in the stomach. Underlying this sensation is an often-overlooked network of neurons lining our guts that is so extensive some scientists have nicknamed it our “second brain”.
A deeper understanding of this mass of neural tissue, filled with important neurotransmitters, is revealing that it does much more than merely handle digestion or inflict the occasional nervous pang. The little brain in our innards, in connection with the big one in our skulls, partly determines our mental state and plays key roles in certain diseases throughout the body.
Although its influence is far-reaching, the second brain is not the seat of any conscious thoughts or decision-making.
“The second brain doesn’t help with the great thought processes…religion, philosophy and poetry is left to the brain in the head,” says Michael Gershon, chairman of the Department of Anatomy and Cell Biology at New York–Presbyterian Hospital/Columbia University Medical Center, an expert in the nascent field of neurogastroenterology and author of the 1998 book The Second Brain (HarperCollins).
Technically known as the enteric nervous system, the second brain consists of sheaths of neurons embedded in the walls of the long tube of our gut, or alimentary canal, which measures about nine meters end to end from the esophagus to the anus. The second brain contains some 100 million neurons, more than in either the spinal cord or the peripheral nervous system, Gershon says.
This multitude of neurons in the enteric nervous system enables us to “feel” the inner world of our gut and its contents. Much of this neural firepower comes to bear in the elaborate daily grind of digestion. Breaking down food, absorbing nutrients, and expelling of waste requires chemical processing, mechanical mixing and rhythmic muscle contractions that move everything on down the line.
Thus equipped with its own reflexes and senses, the second brain can control gut behavior independently of the brain, Gershon says. We likely evolved this intricate web of nerves to perform digestion and excretion “on site,” rather than remotely from our brains through the middleman of the spinal cord. “The brain in the head doesn’t need to get its hands dirty with the messy business of digestion, which is delegated to the brain in the gut,” Gershon says. He and other researchers explain, however, that the second brain’s complexity likely cannot be interpreted through this process alone.
“The system is way too complicated to have evolved only to make sure things move out of your colon,” says Emeran Mayer, professor of physiology, psychiatry and biobehavioral sciences at the David Geffen School of Medicine at the University of California, Los Angeles (U.C.L.A.). For example, scientists were shocked to learn that about 90 percent of the fibers in the primary visceral nerve, the vagus, carry information from the gut to the brain and not the other way around. “Some of that info is decidedly unpleasant,” Gershon says.
The second brain informs our state of mind in other more obscure ways, as well. “A big part of our emotions are probably influenced by the nerves in our gut,” Mayer says. Butterflies in the stomach—signaling in the gut as part of our physiological stress response, Gershon says—is but one example. Although gastrointestinal (GI) turmoil can sour one’s moods, everyday emotional well-being may rely on messages from the brain below to the brain above. For example, electrical stimulation of the vagus nerve—a useful treatment for depression—may mimic these signals, Gershon says.
Given the two brains’ commonalities, other depression treatments that target the mind can unintentionally impact the gut. The enteric nervous system uses more than 30 neurotransmitters, just like the brain, and in fact 95 percent of the body’s serotonin is found in the bowels. Because antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) increase serotonin levels, it’s little wonder that meds meant to cause chemical changes in the mind often provoke GI issues as a side effect. Irritable bowel syndrome—which afflicts more than two million Americans—also arises in part from too much serotonin in our entrails, and could perhaps be regarded as a “mental illness” of the second brain.
Scientists are learning that the serotonin made by the enteric nervous system might also play a role in more surprising diseases: In a new Nature Medicine study published online February 7, a drug that inhibited the release of serotonin from the gut counteracted the bone-deteriorating disease osteoporosis in postmenopausal rodents. (Scientific Americanis part of Nature Publishing Group.) “It was totally unexpected that the gut would regulate bone mass to the extent that one could use this regulation to cure—at least in rodents—osteoporosis,” says Gerard Karsenty, lead author of the study and chair of the Department of Genetics and Development at Columbia University Medical Center.
Serotonin seeping from the second brain might even play some part in autism, the developmental disorder often first noticed in early childhood. Gershon has discovered that the same genes involved in synapse formation between neurons in the brain are involved in the alimentary synapse formation. “If these genes are affected in autism,” he says, “it could explain why so many kids with autism have GI motor abnormalities” in addition to elevated levels of gut-produced serotonin in their blood.
Down the road, the blossoming field of neurogastroenterology will likely offer some new insight into the workings of the second brain—and its impact on the body and mind. “We have never systematically looked at [the enteric nervous system] in relating lesions in it to diseases like they have for the” central nervous system, Gershon says. One day, perhaps there will be well-known connections between diseases and lesions in the gut’s nervous system as some in the brain and spinal cord today indicate multiple sclerosis.
Cutting-edge research is currently investigating how the second brain mediates the body’s immune response; after all, at least 70 percent of our immune system is aimed at the gut to expel and kill foreign invaders.
U.C.L.A.’s Mayer is doing work on how the trillions of bacteria in the gut “communicate” with enteric nervous system cells (which they greatly outnumber). His work with the gut’s nervous system has led him to think that in coming years psychiatry will need to expand to treat the second brain in addition to the one atop the shoulders.
So for those physically skilled and mentally strong enough to compete in the Olympic Games—as well as those watching at home—it may well behoove us all to pay more heed to our so-called “gut feelings” in the future.
There are millions of neurons lining your gut almost as extensively as in your brain – do you think that might have something to do with your mood, your ‘intelligence’, and your overall health? Sometimes called the enteric nervous system, the stomach and intestines have a lot to say about how you feel, or how you ‘stomach’ emotions in general, as well as how well your body fends off unwelcome guests.
The enteric nervous system is so intelligent, in fact, that it houses entire networks of neurotransmitters and special proteins that tell the rest of the body what’s going down – quite literally. It is so wise, that it can operate distinctly from the brain and spinal nerves, and quite often does. Just think of the last time you ate something that didn’t agree with you. Your brain probably didn’t override a sudden urge to purge. Your enteric ‘brain’ knew to get that unsavory meal out of you as fast as possible to prohibit an even more unappealing outcome.
Did you also know that the gut produces more serotonin, the well-known happy hormone, than the brain does? 95% of all serotonin lives in the gut, not in the head. A big part of how we feel every day is truly related to our gut’s feeling, as it digests through the daily grind, our food as well as our food for thought. In fact, irritable bowel syndrome is caused by an imbalance of serotonin in the gut, and is sometimes called the ‘mental illness’ of the brain. We cannot experience an emotion or think a thought without a biological correlation. The brain-gut axis is deeply moved by our daily emotions.
Going further, our gut health is also key to our immunity. Actually, it’s been said that gut flora makes up about 80% of our immunity, and is especially important for infants to bypass illness. Millions of tiny benevolent bacteria live in our large and small intestines as well as our stomachs, and they help to fend off bad bacteria, which can causedisease andeven multiple types of cancer. Often called the ‘second brain,’ our gut is more important than we ever might have suspected.
So how do you ensure a healthy gut? Antibiotics are a major player in the destruction of gut health as they destroy both the bad and good bacteria, so it’s important to avoid antibiotics whenever possible. Luckily, there are numerous natural antibiotics that can be utilized for remedying various resistant infections. In addition to avoiding antibiotics, try implementing these 4 ways to improve gut health.
Our stomachs can often be a mystery to us and many of us don’t realise just how much the foods we eat can impact on our mood and mental wellbeing.
According to charity Allergy UK, a shocking 45% of us suffers with food and drink intolerances, beverage – this is called food intolerance.
Food intolerance is a much more common problem than food allergy and one of the most harmful symptoms can be low mood. 1 in 4 people in the UK will suffer problems with their mood or mental health every year, with anti-depressant prescriptions increasing by over 40% in the last 5 years*.
In a recent paper published in the journal of Nutrition and Food Science, over 81% of patients reported a significant improvement in mood and mental wellbeing as a direct consequence of applying the dietary changes recommended by YorkTest.
So how is it that the food we eat can have such a significant impact on our mood?
Bidirectional connections between the gut and the brain are complex and are regulated in the body in three different ways; through nerves, hormones and the immune system. The gut mediates the body’s immune response; at least 70 per cent of our immune system is situated in the gut and is used to expel and kill foreign invaders.
Our gut contains some 500 million neurons (nerve cells), more than in either the spinal cord or the peripheral nervous system. All of these neurons lining our digestive system do much more than merely handle digestion or cause occasional nervous feelings. Our gut partly determines our mental state and plays key roles in certain diseases throughout the body. Many people will not be aware that 90% of serotonin, the brain’s ‘happy hormone’ is produced in the gut – it is for these reasons that the gut is often referred to as the ‘second brain’.
In addition, research has shown that depression is frequently associated with gastrointestinal inflammation – a common symptom of food intolerance. By tackling unidentified food intolerances, not only will physical symptoms benefit, but mental health symptoms can often show significant improvement.