Gut-Brain link

Today we're going to be talking about a topic that has recently had the research world mesmerized. Hippocrates, known as the father of medicine, once said, let food be thy medicine and medicine be thy food. But what does that mean to the modern day physician, neuroscientist, neurosurgeon? How does it impact on you? People usually talk about a gut feeling, referring to an instinctive response, something that you just know. Recent literature is starting to unravel an important link between the gut and the brain that can influence anything from your mood and behaviour to your health and immune system. Let's delve a little deeper and give you some food for thought. The emergence of the idea of a little brain comes from something called the enteric nervous system and its role in connecting the gut with the brain. It contains some 100 million neurons and embeds itself within the gut wall. The relationship occurs in both directions and, within the scientific community, is referred to as the gut-brain axis. Early work concentrated on how digestive function and the feeling of being full occurs through complex interactions between nerves, hormones, proteins and the hypothalamus, an area of the brain that acts as a control centre for appetite amongst other things. Adding to its complexity, decades of research have introduced the idea of trillions of microorganisms found in the gut as regulators of this gut-brain axis. Recently we've come to understand how the human body hosts multiple colonies and ecosystems of specific groups of microorganisms, including bacteria, yeasts, parasites, virii and protozoa. Different systems including your skin, airway, private parts and gut all have their own little communities of microorganisms that naturally reside in their respective homes. Even more amazing is that these communities have unique variations that are specific to each individual, although we don't know yet what that actually implies. It may seem a bit nasty, but these tiny creatures play a huge role in maintaining our health, having the ability to respond dynamically to changes in the external and internal environments, making them a really intriguing area of research and a promising target for future medicines. First of all, let's talk about the idea of homeostasis. You may remember from your GCSE science that the body is made up of several systems that all require stability and balance. Because the body is a dynamic structure and our internal environment is constantly fluctuating, we don't operate in a static way. Instead we've got feedback loops that monitor and respond to any changes that need to be regulated. To give you a few examples, we maintain our body temperature by shivering or sweating and control our blood acidity using multiple organs including the lungs, kidneys and brain. If for one reason or another something goes really wrong and homeostasis goes out of the window, in one or more of these systems we can become really ill and disease can take hold. This is also true for your gut microbiome. Any disruption that intervenes with your normal homeostasis increases your susceptibility to diseases like inflammatory bowel disease, type 2 diabetes and even anxiety and depression. But how does the actually communicate with the brain? The autonomic nervous system is part of your peripheral nervous system. This nervous system is found outside of the brain and the spinal cord. The neurons there work together to control body functions that you execute without conscious effort. Things like breathing, digestion, the way that your heart beats. Obviously this is a huge system and we can further divide it into two branches called the parasympathetic and sympathetic nervous systems. Generally your parasympathetic nervous system is responsible for rest and digest functions like keeping your heart rate down, getting your gut moving, whilst your sympathetic system is responsible for fight or flight functions. Preparing your body for action by raising your blood pressure, getting your heart rate up and getting your muscles prepared to move. The enteric nervous system in your gut is also a subdivision of the autonomic nervous system and this is the reason why you can feel pain and discomfort from your gut and why the sight and smell of food makes you salivate for example. All these systems work in balance together to maintain homeostasis and respond rapidly both in health and disease especially to inputs such as pain and stress. An important nerve, the 10th cranial nerve or the vagus nerve arises from the brain and is the most direct route that links the gut and the brain. It's mostly composed of nerves that travel either bottom up from the gut to the brain and we call these sensing or input neurons. It also contains nerves that travel in the opposite direction top down from the brain to the gut. We'll call these motor or output neurons. It's thought that depending on the location of the input or sensing nerves they're able to detect stretch and tension in the intestinal wall as well as gut hormones and chemical signals released by microorganisms within the gut. This is how the brain receives some of its feedback from the intestines and provides some explanation as to why you feel hunger, fullness, nausea and pain. These inputs also overlap with emotional states and regulate how you feel. We don't understand how those mechanisms work that well so I'm not going to go into too much detail about it in this video but it may be something to talk about another day. In the other direction output neurons have been shown to have an anti-inflammatory role. In disorders that affect bowel function reduced parasympathetic activity of the vagus nerve is associated with abnormal overgrowth and relocation of bacteria normally found in the small intestines. Otherwise in experimental animals lacking a gut microbiome factors such as body weight, intestinal function, anxiety behaviours, all of these things are abnormal compared with their healthy counterparts that have a proper microbiome. This may have implications for babies born via caesarean section for example because they may not pick up the same microbes as babies that are born vaginally. Researchers think that this may make caesarean section babies more likely to develop diseases like obesity, asthma and eczema. But any differences in the gut microbiome between these two groups caesarean section or non-caesarean section disappear in the long term regardless of birth method. There may still be something to the idea of transferring microorganisms from mother to infant before birth but we still don't even know the point at which the gut first becomes colonized. Is it before or after birth? There's still a lot of research that needs to be done before we can say anything with certainty as with anything but before we move on I want to tell you about something called faecal transplant which sounds really nasty but is actually quite amazing. This is when the intestinal microbiota from one individual is transferred to another. A 2020 study showed that a human faecal microbiome transferred from patients with alcoholism on antibiotics actually caused anxiety-like and depressive symptoms in the mice. This just shows how powerful the gut microbiome is and the way it can affect body physiology and brain functions. Similar experiments showed that mice without a gut microbiome can become healthier following a faecal transplant from normal mice. Those mice gained healthy body fat and reduced their food intake. This method has also been used therapeutically to successively treat stubborn clostridium difficile infections in humans. Now this is a horrible bacterium that can cause severe diarrhea, high temperature and stomach pain and can actually be life-threatening if left untreated in certain patients. Just goes to show that faecal transplant may be nasty but it's been an interesting addition to the microbiome literature. This has been a bit of a crazy complicated and interesting topic and I hope you've learned a thing or two about the gut-brain axis. Let me know what you found interesting about this in the comments section down below. Don't forget to like it and I'll see you at the next video.