What is the second brain?
The cells in our brain are known as neurons, and act to regulate and interpret the information we receive from the world around us. Neurons reside in our brains and spinal cords – along with the 500million of these crucial cells residing in our guts, connecting via nerves to our brains. The neurons of our gut make up the enteric nervous system (ENS), lining the gastrointestinal tract from our esophagus all the way to the rectum. While the main role is to control digestion, we do know the ENS can communicate back and forth with our brains.
The largest nerve carrying information between the brain and ENS is the vagus nerve (the longest of the 12 cranial nerves), facilitating bi-directional communication. The nerve is the main axis between our brains and our guts, monitoring homeostasis (the state of steady internal, physical, and chemical conditions) and connecting our emotions and cognition with the digestive system – regulating immune activation, reflexes and signalling. These lines of communication allow the brain to influence the activity of ENS cells which are, in turn, under the influence of gut microbiota.
What is the microbiome?
Within our gut lives trillions of bacteria, fungi, viruses and yeasts – collectively known as the microbiome. These micro-organisms exist on a spectrum; some are pathogens, only becoming harmful if they increase in number or get into the wrong part of the body. Others are incredibly helpful, programming our immune systems, preventing harmful micro-organisms from taking root, and feeding our cells. But how do we acquire a microbiome? The short answer is we don’t fully understand how a person’s microbiome comes to be. Currently, it is thought that during birth we are acquiring microbiota as we leave the birth canal. After this, our microbiome begins to change rapidly and is shaped by breast milk and the environment. By the time a child is three years old, the microbiome is relatively stable; but our diets, stress, substances we imbibe, and the environment all continue to influence our microbiome, altering it as we age.
Different parts of our bodies have different microbiome populations and differ between people. In particular, diversity in the gut microbiome influences how people react to food – so you can blame that next dairy-stomach-ache on the micro-organisms populating your gut. Our gut microbiome continues to be linked to a range of diseases and conditions, including anxiety, obesity and even diabetes. It can also dictate how a person reacts to different drugs and therapies, how we sleep, and might even dictate sex differences in hormones and immune systems.
The microgenderome: sex differences in our microbiome
Emerging evidence suggests there are sex-differences in our microbiome, impacting interactions with our brains and other systems of the body. Could this then be behind the differences in how diseases affect men and women? In women, autoimmune disease and irritable bowel syndrome are significantly more common – and even when men and women share the exact same diet, we still see sex-specific responses in the gut. While the scientific community hasn’t yet been able to fully define these sex-differences – nor completely understand they mean for disease onset and progression – we do have some knowledge about sex-dependent gut microbiomes.
The differences between the male and female immune system are well recognised, and the majority of our immune cells respond to specific sex hormones. Women have a predisposition to autoimmune disorders, with some reasoning the microbiome – acting as an axis between our immune system and sex hormones – may play a part. Our microbiome is also impacted by the therapeutics we take, with men more likely to take heart medication and women commonly prescribed oral contraceptives; all of which impact our microbiome and may be another factor in sex differences. The kicker? Most studies show that many differences between the male and female microbiome are present after adolescence, through middle age and are then eliminated in studies where participants are over 60 years of age. In other words: these differences are present only during the years of circulating female sex hormones, post-menopause.
We’ve all heard it said that girls mature faster than boys (we also know this is not a green card for immature behavior…), and we also see this reflected in the gut: where the microbiome of women matures earlier than that of men. When considered in light of women optimising brain networks earlier in life, the role of the brain-gut-axis continues to assert its importance in mood, behaviour and neurodegenerative disorders.
Microbiomes on the brain
The links between our digestive systems and our brains have been on the research agenda since the 19th century, yet it’s only been in this century that researchers have taken the notion seriously. We already have anecdotal evidence for the brain-gut connection; where feelings of anxiety or distress can result in our stomachs knotting up, and intestinal distress sending signals to our brains to trigger these feelings. Scientifically speaking however, the pathways through which our gut and brain are connected by microbes are still not completely clear. Some known mechanisms are:
- Interactions with our immune cells in the gut: this prompts these immune cells to create cytokines (cell signalling molecules), circulating to our brains via the blood stream. Cytokines are crucial for signalling the immune system and controlling the body’s inflammatory responses.
- The production of neurotransmitters and metabolites: the ENS can create more than 30 different neurotransmitters – the molecules that carry information between neurons – and the hormones and peptides released by the ENS are interpreted by our brains to regulate appetite and food intake. These tiny signalling molecules are chemical messengers, used by the nervous system to transmit information. The molecules produced by the gut can enter the brain to alter the activity of cells residing there.
- Interactions with enteroendocrine cells: producing the molecules interacting with the vagus nerve. These trigger the nerve to send signals to the brain and result in a mood or behaviour change.
Scientists have increasingly shown that stress in mice can alter the microbiome, a phenomena that may be mediated through these pathways. Alternatively, when mice are given a specific bacterium that influences the immune system, stress behaviours decrease and brain chemistry altered. Importantly, the animals that had a severed vagus nerve did not exhibit these changes; suggesting the nerve plays a role in our experience of mental stress. The make-up of our microbiome can even result in less cortisone being produced, again leading to reduced anxiety- and depression-related behaviours. Interestingly, we know that stress can inhibit signals from the brain to the ENS via the vagus nerve, causing gastrointestinal problems.
The link between the ecosystem of the gut and our moods has also been established in those living with depressive disorders. A study from 2019 found that several species of gut bacteria are missing in those with depression, compared to people without. While these findings don’t prove causality – i.e., that certain microbes can cause or prevent depression – researchers are now looking to see which brain pathways these microbes are associated with. Coprococcus in particular is a gut-bacteria that has pathways related to dopamine, a key neurotransmitter in depression, and can also create anti-inflammatory molecules implicated in the disorder.
Scientists have also investigated the impact of the gut microbiome on neurodegenerative disorders, such as Alzheimer’s dementia, multiple sclerosis and Parkinson’s disease. In people with Alzheimer’s disease the diversity of the gut microbiota is significantly reduced, and the increase or decrease of specific species was correlated with the types of dysfunctional proteins in the brain. These people also display high levels of specific inflammatory mediators in the blood, creating a link between certain gut microbiota and brain markers of disease. We see these results replicated in mice with genes that trigger Alzheimer’s, having differing populations of gut microbiota. This has even been shown to be linked to changes in behaviour, memory and thinking.
Similar findings have been observed in Parkinson’s Disease, where sufferers have a different composition of gut microbiota. Interestingly, transferring the microbiome of a mouse with Parkinson’s to that of a normal mouse can lead to impaired motor function and reduced dopamine in the brain. Parkinson’s patients frequently report feeling constipated or other gut issues, and specific intestinal infections also influence disease progression: Helicobacter pylori commonly causes gastritis and ulcers, and has also been linked to worsened motor movement in Parkinson’s. The condition ‘small intestinal bacterial overgrowth’ is also linked to worsened fluctuations in motor movement, and causes symptoms of bloating, weight loss and abdominal pain.
New treatments on the horizon?
It stands to reason that if we simply target the microbiome in these conditions, we should be able to treat symptoms and onset – right? Not quite. Whether these associations are truly a cause-and-effect relationship remains to be definitively proven. Because our gut microbiome interacts with so many systems and pathways of the body, teasing out whether microbiome changes are causing disease or a result of it is the ultimate ‘chicken or egg’ question. In the meantime, promising finds from mood disorder studies suggest dietary habits can improve the experience of anxiety, chronic stress and depression. So, what lifestyle changes can you make to give your microbiome a boost?
- Take probiotics and include fermented food in your diet. Probiotics can support a healthy, diverse gut microbiome and may even prevent inflammation. Probiotics can be naturally found in fermented foods, such as fermented vegetables; kimchi; kombucha; miso; sauerkraut; tempeh and kefir.
- Include 40g or more of fibre in your daily diet. Particularly, prebiotic fibre has been shown to help probiotics be more tolerable for the gut to process. To reap the benefits of this combinatory effect, include more asparagus; bananas; onions; whole grains; garlic; artichokes; and chicories in your diet.
- Choose foods that are high in polyphenols (micronutrients that naturally occur in plants) can also fuel beneficial microbes. These antioxidants can be found in berries, olive oil, green tea, coffee and nuts.
- Studies have also shown that a vegetarian diet may improve gut health, due to the large amount of prebiotic fibre it contains. Participants in one research study demonstrated lowered levels of gut inflammation after switching to a vegetarian diet, linked to altered gut microbes. The variety of fruits and vegetables is also critical for supporting different microbial species.
- Reduce your intake of artificial sweeteners. This is critical for encouraging a healthy gut ecosystem. Studies in mice have shown that the standard Western diet – high in sugars and fats – negatively affects the gut microbiome and may be linked to stress behaviours. The artificial sweetener aspartame can even increase the number of some strains of bacteria that are associated with metabolic disease.
- Ensure you are only taking the medications and antibiotics that you need to, with consultation with your doctor. These therapeutics are necessary to combat infections and certain conditions; but overuse can lead to antibiotic resistance, damaging the gut microbiota.
- On that note, try to avoid unnecessary food and vitamin supplements. Rather than increasing the health of your gut microbiome, very few of these have been shown to have any benefit and may in fact lead to imbalances in gut flora.
- Stay away from smoking; smoking affects not only your heart and lungs, but also your gut health. Smoking can increase potentially harmful microorganisms in your gut, while decreasing the beneficial ones.
- Sleep! It can’t be said enough; good quality sleep is beneficial for all realms of health and wellbeing. Irregular sleep habits or disturbed sleep can increase the risk of inflammatory conditions, linked to disturbances in gut flora.
- Exercise has the potential to increase the diversity of species in our gut microbiome, with some studies suggesting athletes have a greater variety of gut flora. Yet it’s still not clear whether athletes simply eat a different diet that may be contributing to this difference.
- It’s important to remember that many cleaning products we use in the modern world can alter our gut microbiota. Using disinfectant cleaning products frequently – at least twice a week throughout the household – can increase the presence of gut microbes that are linked to type 2 diabetes and obesity.
- Get dirty! Spend time in nature and in the countryside, be near animals and avoid being too hygiene obsessed. Rather than being a green light for dropping your cleanliness standards, consider loosening up if you fall in the category of ‘clean freak’. Gardening and being near soils, outdoor activities and living in rural areas are all linked to the increase health of the microbiome, while studies of those living with cats or dogs show increased microbial diversity.
While lifestyle changes can greatly enhance gut health and overall wellbeing, if you notice gut symptoms correlating with any mental or neurological issues it’s critical to speak to your doctor immediately. Maintaining a healthy gut microbiome goes beyond the physical experience of indigestion or obesity: the gut and its microbes play a critical role in our moods and the health of our brains.
Biology of the Brain: How Your Gut Microbiome Affects Your Brain