Psychology and Neuroscience of Affective Disorders Lecture PDF

Module: Psychology and Neuroscience of Affective Disorders Week 3: Biological alterations of affective disorders Topic 1: The role of the gut microbiota in affective disorders (Part 1 of 4) Lecture transcript Viktoriya Nikolova, PhD student Department: Centre for Affective Disorders, Academic Psychia...

Module: Psychology and Neuroscience of Affective Disorders Week 3: Biological alterations of affective disorders Topic 1: The role of the gut microbiota in affective disorders (Part 1 of 4) Lecture transcript Viktoriya Nikolova, PhD student Department: Centre for Affective Disorders, Academic Psychiatry Slide 5 Hello, everyone. My name is Viktoriya Nikolova, and I'm a final year PhD student at the Centre for Affective Disorders at King's College London. My PhD project is looking at the role of the gut microbiota in depression and the potential of probiotics as a novel treatment. So in this lecture, I'm going to talk about the role of the gut microbiota in affective disorders. Slide 6 And now to briefly outline what the lecturer will look like. In Part 1, we will answer the questions. What is the microbiome? Why should we study it? And how is it relevant to mood disorders? Then, in Part 2, we will cover some of the findings from observational studies examining how the gut microbiome differs between people with and without mood disorders. Then, in Part 3, we will look at the possible mechanisms through which the gut and the brain communicate, and how those mechanisms impact mood, cognition, and behaviour. And then, finally, in Part 4 we will review some of the main novel interventions and treatment strategies emerging from our knowledge of the role of the gut microbiome in these conditions. © King’s College London 1 Slide 7 First, I wanted to give you a little bit of a background in terms of our place as humans in the context of the microbial world. And then I wanted to show you an example. I think you'll find interesting of a case known as "the boy in the bubble". So this is just a quick schematic on the left of what our bodies and organs look like if we only look at their cellular and genetic makeup. In the middle part, you can see what happens when we actually look at our bodies in terms of the bacteria that is residing in and on us at all times. The human body contains trillions of microorganisms, and in fact, they outnumber human cells by 10 to 1. The total weight of microbes in and on our bodies is somewhere around 1-3% of the body's mass which has commonly been averaged to three pounds, which is actually very similar to the weight of the brain. Slide 8 So the microorganism ecosystem or community in different locations in our bodies is called the microbiota. In this lecture, we'll focus entirely on the gut microbiota. However, it's useful to know that we have a number of other microbiotas including, for example, the oral cavity, the nostrils, the skin, etc. Some of these are connected, and some are not. For example, bacteria can freely translocate or move from the oral cavity to the gut. And what we refer to as the microbiome, which is also a term you'll probably see a lot in the literature, is the community of microorganisms and also their environment as well as their genetic makeup. Although the definition of this term varies somewhat and you can also see it interchangeably with microbiota. Slide 9 And before we proceed, what about the boy in the bubble? This is a story of what we now consider to be a very unethical experiment. It was based on the general assumption that all microbes are bad. We now know that microbes can in fact be differentiated. Yes, it's harmful, but also is neutral and even beneficial, depending on their function. So David was born with a serious immune deficiency condition that he inherited from his parents. In fact, his parents were convinced by their doctors to have him, even though they knew they would be passing this condition to him. This is because the doctors had developed a new paradigm that they wanted to try. One of a germ-free bubble in which he would be raised in a micro-free environment and possibly spend his entire life in there unless a transplant was found. So this means that he would not be able to experience direct human touch or human contact other than through these membranes you can see around him those black things in which, for example, the doctor has placed his hand in the right image. Needless to say, David became very, very depressed and very unhappy. They eventually did find a transplant for David when he was 12 years old, meaning he spent 12 years inside the bubble from his sister. And even though he didn't really reject the transplant, he died a few months later nonetheless, because of a dormant virus, that was in her blood that was undetected. So we constantly carry potentially harmful pathogens like this in our bodies, but because we have strong immune systems, they don't become a problem. However, if we don't, they can become a really lethal problem. 2 © King’s College London Slide 10 And what we have learned from this particular experiment is that living in a microbe-free world doesn't allow our bodies to develop a strong immune system. So in this case, David's immune system, which already had a pre-existing condition, would have been developed in such a deficient way that it stood no chance against virus pathogens in the real world. And now that we have seen how important bacteria and by extension, the microbiotas are to our lives, let's move on to talk about the gut microbiota. Slide 11 So let's now focus more specifically on the gut microbiota. The gut microbiota is the community of microorganisms that reside in our gastrointestinal tract and the exact composition of the microbiota changes throughout our life spans. The gut microbiota is influenced by a number of external and internal factors, and I want you to think of it really is a dynamic ecosystem. So just like the ecosystem, we as humans live in, it's impacted by many factors like geographical location, pollution. In this case, what we eat, what we drink, whether we smoke or take medication also from things like whether we have pets because having a pet increases the diversity of bacterial availability in our environments. And it's also impacted by other internal processes like various diseases our genetic makeup and so on and so on. And this is not to say that because this system is constantly changing and can be impacted by so many factors, we cannot find effective and longer-lasting ways to positively change it, especially if things are going wrong. It is just to say that we need to be mindful of these factors and attempt to control them as much as we can, or at least account for their impact. Slide 12 I already mentioned that the gut microbiota is vital in the early stages of life when the immune system is being developed but what are some other functions of gut bacteria? For one, they provide the host with important nutrients as they aid digestion, including helping us metabolise indigestible compounds such as fibre, which are very beneficial as they produce essential short-chain fatty acids. Just briefly these are compounds that help maintain the health of the cells of the gut lining, support our immune system functions, and protect against diseases of the digestive tract. Gut bacteria also defend against colonisation of opportunistic pathogens. They contribute to the development of the intestinal architecture. They regulate the immune system throughout the lifespan, and they also produce neurotransmitters, which of relevance here are involved in mood regulation, for example, serotonin, and they also maintain the intestinal barrier. Slide 13 Maintaining a healthy intestinal barrier or gut lining, that is one that doesn't allow bacteria to translocate from the gut to the surrounding environment, which is a condition known as leaky gut, is important as it has been linked to a number of inflammatory-related physical and mental health conditions such as irritable bowel syndrome, inflammatory bowel disease and of course, depression and anxiety. And as I suspect you already know from other lectures in this module, a state of chronic low-grade information has been linked with these and other mental health conditions as well. 3 © King’s College London Slide 14 And the last term we need to define before we proceed to the next part of this lecture is the so-called gut-brain axis or microbiota-gut-brain axis. These are two variations of the same term that are used interchangeably. We're going to discuss more about its specific parts in the following lectures, but I just wanted to define it for you as essentially the complex bidirectional communication between the gut and the brain, which spans multiple systems, including the central nervous system, the endocrine system, the immune system, and the sympathetic and enteric nervous systems as well. And just to remind you what we mean by enteric nervous system is the millions of neurons lining the gastrointestinal tract, which has led many to describe the gut as our second brain. And we will go into the different components of the gut-brain axis and how it impacts mood disorders in the following sections. 4 © King’s College London