All right. So this lecture we're going to tackle the microbiome and inflammation. So first some definitions. Immunology. Immunology is the study of the physiological mechanisms that humans and other animals use to protect or defend their bodies from pathogens or injury. Immune response is the reaction of cells and fluid to the body to the presence of a substance which is not recognized as a part of the body itself. So innate versus adaptive immunity. We're going to talk for a minute about immunity because it's the immune system that underlies inflammation and it's inflammation that underlies a lot of the disease states we've talked about in these different modules. So we're going to dig down the details for a second on adaptive versus innate immunity. Adaptive immunity refers to antigen specific immune response. When an antigen has been recognized the adaptive immune system creates an army of immune cells designed to attack that antigen. Adaptive is learned or immune memory like the chickenpox vaccine for example that's how that works. So innate immunity refers to cells and mechanisms that provide the first line of defense from infection in a non-specific manner. So adaptive immunity, specific or learned, innate is non-specific. These responses are rapid and independent of an antigen. When you get a cut for example your body reacts by sending immune molecules to the site of infection to protect you. So mostly we're going to be focused on the innate immune system. So cytokines, what are cytokines? Cytokines are the main way of measuring information in humans. So for example, in most of my research now we collect a cytokine panel by testing the blood that we collect from each one of our participants. The cytokines give us a way of measuring how much inflammation is going on. So all immune cells produce cytokines. Pro-inflammatory cytokines ramp up when the immune system is active. Anti inflammatory cytokines downregulate immune system activity. Cytokines regulate immunological responses and cell-to-cell communications as well as host responses to infectious agents and inflammatory stimuli. These cytokines interact with each other in complex ways, sometimes they can be additive, sometimes synergistic, sometimes antagonistic. One might induce the activation of another, so this is a complex system that indicates inflammation. All right. So what about the microbiome and specifically what about the microbiota gut brain axis? What in the world is the microbiota gut brain axis? Well, the first thing you need to know is that we carry around with us in our gut a bunch of microbiota, bacteria. Some people, some scientists like to say that the amount of bacteria you contain in your gut basically weighs about as much as your brain, and that bacteria, the balance of the good bacteria, the bad bacteria basically impacts a number of different systems throughout the body that is related to inflammation and can impact the brain as well. So that's why I talk about the gut brain axis, right? It's basis is bidirectional communication between the GI tract, endocrine system, and a whole bunch of other systems including the central nervous system. The quantity and composition again of those bacteria in your gut basically is critical for how this gut brain axis functions. The immune system is also fundamental to how all this works together. So accumulating evidence suggests bidirectional communication between the gut microbiota, the brain, and the immune system. So basically if the gut microbiota gets out of control you're going to see increases inflammatory signaling, increases in cytokines, and which in turn can impact brain function. This is a nice little graphic and throughout this lecture I have graphics from nice review papers, but this just shows you what we're talking about here. In terms of healthy gut function and a healthy central nervous system versus abnormal CNS activity, and abnormal gut function. So these things work together, right? You can read over here about the impact of stress and disease and of course this is all about the healthy side of things over here. So if you want to read more about this, this is a nice review. You can look up in Nature Neuroscience Reviews. Here's another illustration of how this works. What you've got down here is you've got your bacteria. There are different kinds of bacteria good ones and bad ones living together in your gut. Basically, what happens is that there's this communication that basically can increase cytokines, and activate the immune system, and increase inflammation that's sending signals to the brain, and the brain can send signals back down, and the impact functioning of the GI tract impact the microbiome. So people are very interested in this. There's a number of studies now linking this gut-brain axis with things like obesity, not surprisingly, depression, anxiety, pain, autism, MS, cardiovascular disease. As we go on you'll see not just those things but also Alzheimer's. So this is a very important area of work. So this gives you another example how these things work, right? Cancer patients for example, are going through chemotherapy that can mess up all kinds of things up and down this axis here, right? Again, comparing this to a healthy functioning gut-brain axis. Again you can read more about that in this journal citation down here at the bottom. So in summary the immune system in particular innate immunity plays a critical role in terms of defending the body and as a result produces inflammation. Part of the inflammatory response is the secretion of cytokines, which can be pro-inflammatory or anti-inflammatory and they produce a variety of effects in the brain and the body. The state of the gut microbiome is also super important in terms of the activation of the immune system and inflammation. Changes and inflammation in the microbiome have been linked now to a number disease states which we are focused on in these various modules which is why we're doing one module just on inflammation and the microbiome.
