The enteric nervous system (ENS), the nervous system that innervates our gut, is fairly extensive and plays an important role in both our physical and brain health.
If you’ve read many of our other posts, you know that we like to take a systems-level (or "holistic") approach when talking about brain health. In contrast to reductionist science which looks at a small portion of a larger system in isolation from all other parts of the system (which, to be fair, does have its place sometimes), we recognize that all elements of the system are essential to building an understanding of how the system works as a whole. No matter how many duplicates of a single puzzle piece you have, you can’t put together a full picture without each unique piece of the puzzle.
With this in mind, we find the topic of how the gut microbiome affects brain function to be fascinating. As the scientific community learns more about the bacteria, fungi, viruses, and other microorganisms living within us, we are realizing how our gut ecosystem is responsible for (or at least correlates with) conditions related not just to the digestive system, but also heart health, weight, diabetes, the immune system, and brain function (just to name a few). Anxiety, depression, Alzheimer’s Disease, Parkinson’s Disease, ALS, sleep disorders, brain fog, and Autism are but a few of the many impacts gut microbes can have on your brain. The increasingly recognized importance of gut health on brain health has led some experts to call the gut the second brain, while others go as far as calling it the first brain. From a systems-level viewpoint, I see neither as being first or second, but rather the two are highly connected, interacting, and function interdependently.
Our understanding of this relationship may not yet be completely understood, but there are a few things that we know for sure. We know that the residents in our gut are responsible for manufacturing at least some of our neurotransmitters such as serotonin, dopamine, GABA, and acetylcholine. Interestingly, it’s not the microbes themselves that are manufacturing these neurotransmitters, but an article published in Cell found that the microbes stimulate the human gut cells to produce the chemicals. Thus you can think of your gut microbes as a sort of ecosystem engineer—they are interacting with their environment (your body) in a way that alters the ecosystem in which they are living. This complex interaction is far from being well-understood, but based on principles of ecology appears to be a symbiotic relationship in which both organisms benefit (at least when we have a healthy gut community). Why we rely on other organisms to tell us to produce chemicals for our own use is a great question. Unfortunately, we have no answer for that, but the fact that this relationship exists demonstrates the complexity of life in general and again the importance of looking at a whole system instead of just individual parts. It also makes you wonder what else our microbes are telling us to do that we don’t know about!
Recent research has shed some light on more of the complex interplay that exists between microorganisms and the host’s gut. A recent publication from a group at Cal Tech provides a relatively succinct review of our current understanding of the communication network between the gut and the brain and how dysbiosis can interrupt normal functioning, particularly with respect to microglial cells in the brain (if you’re interested in the topic, their paper is a great place to start for more in-depth information). To oversimplify things, our gut microbes both directly and indirectly communicate with the microglia in our brains via the vagus nerve, the circulatory system, and the immune system, and have a large hand in controlling the up- and down- regulation of inflammation in the brain and body, thus influencing the development of many (if not all) chronic diseases.
Let’s break that down a bit:
The most direct form of communication between the microbiome and microglial cells is via the vagus nerve, which innervates the gut in thousands of places and creates a highway of messages from the gut to the brain and vice versa. Metabolites or other chemical substances created by the microbes can directly stimulate nerve endings in the gut, and those signals are then transferred to the brain, where the inflammatory state of microglia can be influenced.
A bit less directly, microbes communicate via interactions between the circulatory and immune systems, starting at the gut. As shown by Karczewski and his team, gut microbes are at least partially responsible for modulating and regulating the permeability of the gut lining. When dysbiosis occurs (either through microbial community composition or insufficient activation/communication between microbes that are present) the host can develop a “leaky gut.” Mechanisms of this condition are beyond the scope of this article, but at the functional level, it means that the cells of your gut, which are supposed to regulate what gets absorbed into the bloodstream behind them, become less tightly packed. Tight junctions between cells open up, allowing for unregulated passage of large or dangerous substances (undigested food, microbes, toxins, etc.) from the gut into the bloodstream where they don’t belong. Concurrently, a group at the University of Gothenberg in Sweden found that microbial community composition affects the mucus layer on top of colon cells. A thicker layer means it’s harder for bacteria or toxins to leak through, regardless of the state of the tight junctions below (the paper also highlights an important point about how significant microbial differences may be unknowingly present in lab mice that are otherwise identical, bringing into question the validity of using them as a model species, but that’s a whole different topic).
It shouldn’t take an expert to predict that a leaky gut could cause problems, and in fact, it does. This occurs most directly in the form of allergies and food intolerances as your body’s immune system attacks the undigested food particles floating around in your bloodstream. This also leads to systemic inflammation—even the healthiest of foods can become a toxin to your body if they are not fully digested and broken down as they should be before entering your bloodstream. While acute inflammation can be a good thing to help clean up an acute problem, if your gut lining is perpetually leaky and you are constantly inducing inflammation whenever you eat, that acute inflammatory state becomes chronic, which can aid in the development of a wide range of chronic diseases (Type 2 Diabetes, heart disease, asthma, arthritis, cancer, etc.).
Less directly, when your gut wall is not able to control what gets through, the same compounds that induced leakiness in your gut can enter the bloodstream and interact with other membranes/barriers within your body such as the blood-brain barrier. The combination of a more permeable blood-brain barrier and undesirable substances in your bloodstream means that those same inflammatory compounds can then make their way into your brain and activate microglia directly, causing the release of more pro-inflammatory cytokines in an effort to again clean up the mess that has been made. Again, acute inflammation can be a good thing, but chronic inflammation due to continuous bombardment of your system with irritating compounds can then lead to the development of chronic disease/conditions (remember the HSV-1 theory of Alzheimer’s Disease? If not, read about it here). In fact, a recent study published in Nature showed that capillary damage in the brain (which could be from loss of membrane integrity) and blood-brain barrier breakdown were present in individuals with early cognitive dysfunction, even when Aβ and tau (the conventional biomarkers of Alzheimer’s Disease/cognitive dysfunction) were not present. This supports the theory that Aβ and tau are not the cause of Alzheimer’s Disease, but rather a downstream effect of leaky membranes. Alzheimer’s Disease is far from the only problem that can arise from a leaky blood-brain barrier, but we’ll go into more details about other diseases in later posts.
The scientific community is constantly making new discoveries of the extensive and complex relationship between microbes and human health. This extremely introductory and over-simplified article hardly scratches the surface of the topic, but we’ll go into more details on more specific topics in later posts. The main takeaway from all of this information might be realizing that our microbes cannot be ignored when considering human health. Since everyone’s microbiome is different in terms of both community composition and species quantities, getting a good reading of your own personal health is extremely important. While there are some broad generalizations that apply to most people, it’s also true that food, drugs, supplements, sleep, exercise, and other lifestyle and environmental factors can affect everyone slightly differently depending on your specific microbiomes (keeping in mind that microbes are everywhere, not just in your gut!). Thus, tracking your own personal reactions (using tools like the Brain Gauge) to lifestyle and environmental factors is really the only way to determine how you, specifically, can reach your optimal health.