The gut and the immune system. Did you know they are best friends? Really. If you haven’t heard, gut health is hot news these days. As research continues to show more and more, the gut plays an integral part in immune function and development. In fact, up to 70% of the body’s immune cells reside in the gut (1). There are sections of the intestinal wall called the gut-associated lymphatic tissue (GALT) which include clusters called Peyer’s Patches. Peyer’s Patches are just concentrated areas of immune system cells. These cells are much like a surveillance team, watching and waiting for any sign of trouble.
These statements have not been evaluated by the FDA and are not intended to cure, diagnose, treat, or prevent any medical condition. This is just my own personal research.
How does the immune system work? Well, the immune system is one of the most complex systems in the body. It would take numerous graduate level courses to really understand its depth and complexity. However, here I will cover a little snapshot. First, let’s break it down into two departments: adaptive and innate.
The innate immune system functions much like the first line of defense on the battlefield. It is immediate, it thinks fast, and it does not have time to be too precise or specific about what it is doing. It’s job is to control the situation quickly and block the attack.
The innate immune system is the body’s initial defense mechanism that is always ready and always active. It takes action at first sign of trouble. It responds to a specific type of protein called a cytokine that the damaged or attacked tissues release.
Some (not all) participating members are:
- Neutrophils-these cells come from the blood stream, swarm the problem area, and begin sending off signals for help while killing the offending pathogens
- Macrophages-these cells live in the tissues and “eat” pathogens
- Natural killer cells-these cells cause infected or abnormal cells to implode
When this system is activated, the manifestation is inflammation. Inflammation is the body’s way of fighting infection. Acute inflammation is not necessarily a bad thing.
Now, let’s talk about the other department.
The adaptive immune system functions like the intelligence team working behind the scenes. It must be debriefed about the situation and given time to come up with an attack plan. It is much more specific in how it works; however, this can take days.
The adaptive immune system is the body’s secondary defense system; it takes a few days to activate. It has a specific target and a specific goal. This is the system involved with creating antibodies and responding to vaccines.
Two main players:
T lymphocytes- these cells find, attack, and kill
B lymphocytes- these cells produce antibodies
T lymphocytes attack and kill specific cells in the body that either contain a foreign substance or are known to be unfamiliar and dangerous. Ironically, they must be able to attack other cells recognized as “self” in the event that the other cell is compromised. (2)
B lymphocytes are involved with antibody production. What is an antibody? A handy little protein designed to attach to a specific target. The body sees that antibody attached to the target and knows the target must be removed or destroyed. Antibody production takes a few days to happen; the body is responding with a weapon against a new and specific target. It needs time to create this weapon. After an antibody is made once, the body is prepared to make it again and it will not take as long the second time.
That should be enough immune system to get to the main point of this post; how is the gut microbiota involved in all of this? The gut microbiota is the collection of microorganisms that live on your intestinal wall. This is crucial for immunity. The impact of the microbiota regarding immunity is two-fold—development of the immune system and function of the immune system.
The gut microbiota can direct immune system development. For example, Bacteroides fragilis, a bacteria, produces a protein called polysaccharide A that directs cellular and physical development of the immune system (3). An underdeveloped immune system may have many flaws including immature Peyer’s Patches (1), a lowered neutrophil count (1), and decreased antibody production (3).
The microbiota can also contribute to the function of local and systemic immune function (1). This is important in the development of autoimmune conditions because many times these conditions affect the body as a whole. Localized immune function would be concentrated in one area of the body, while systemic immune function covers the entire body. Autoimmune disease may manifest as the adaptive immune system attacking “self” (2). There is strong evidence that the microbiota is involved in autoimmunity, and it is believed that some organisms can induce disease while others prevent it (2).
Inflammation is another aspect of immune function that can be affected by the gut microbiota. It is believed that there are molecular interactions between the organisms of the microbiota and the immune system (3), just as there are interactions between the tissue cytokines and the immune system. This communication is thought to take part in managing inflammation in the body (3). Inflammation, although necessary in some cases as the body’s defense, can be a huge problem when it is it left unchecked and becomes a chronic issue. When inflammation becomes chronic, it can lead to a great deal of other health struggles.
Much of what researchers know about how the gut microbiota relates to the immune system comes from a science called gnotobiology: the study of germ-free animals. These animals are sterile in that they do not have any bacteria in their gut. By studying the immune system of germ-free animals, many times mice, researchers have been able to pinpoint some of the actual relationships the immune system has with the gut microbiota.
In these studies, the germ-free mice have been shown to display immune defects at the tissue, cellular, and molecular levels (3). Some examples of this included underdeveloped Peyer’s Patches(1), defective antibody production (3), and a lowered neutrophil count (1).
Germ-free mice were more susceptible to infection and had defective T-lymphocyte function (3) as well as decreased numbers of T-lymphocytes (1). Also, reduced B-lymphocyte numbers in the Peyer’s Patches were noted (1).
Interestingly enough, when the gut bacteria were reintroduced in the mice, their immune systems began developing properly and all function was restored (3).
Another study found that when bacteria was introduced into the guts of germ-free mice, an inflammatory response arose. This inflammatory response was absent in normal animals with a healthy gut microbiota when they were exposed to new bacteria (4). This suggests a homeostatic relationship between the organisms of the gut microbiota and immune system (4).
Homeostasis: the tendency toward a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes.
The Balanced System
So how does this all relate to inflammation and autoimmune disease? As you can see, the gut microbiota and the immune system are intricately related. The immune system needs the microbiota for development and function, and the microbiota needs the immune system for survival. This system is delicately balanced and complex because the microbiota is capable of both inducing inflammation and preventing it (3). Even when a single microbial species is removed or added, this unbalanced gut can tip the scale from normal function to inflammation, autoimmune disease, and allergies (1).
How do probiotics play into this?
Some Innate Immune System Benefits
Assisting in inducing inflammation and preventing inflammation is one way probiotics may be of benefit. Cytokines are the messenger proteins of the immune system. They can be both pro-inflammatory (causing inflammation) and anti-inflammatory (reducing inflammation).
A popular and well-studied probiotic genus, Lactobacillus, interacts with epithelial cells in the gut to produce cytokines that cause inflammation (4). Why would we want to cause inflammation? Sometimes the body needs inflammation to fight off an infection.
Probiotics may also have anti-inflammatory capabilities. Pro-inflammatory cytokines in mice with inflammatory bowl disease were suppressed with the introduction of probiotics (4). Anti-inflammatory cytokine production has been induced by interaction of the immune system with polysaccharide-A, a protein produced by a specific bacterial strain (2).
Some Adaptive Immune System Benefits
T-lymphocytes can be extraordinarily helpful in fighting infection but can also cause a great deal of trouble in regards to autoimmune disease. Probiotics have been shown in mice to suppress T-cell production (4).
B-lymphocytes produce antibodies. There is a specific antibody (called immunoglobulin A) that lines the barrier of the gut and serves as a protective layer; excellent evidence exists that production of this antibody may be increased with the use of probiotics (4).
In humans, probiotics (especially Lactobacillus and Bifidobacterium species) have shown promise in encouraging proper immune system development, regulating cytokines, and assisting in rebalancing the gut microbiota (5). It is important to realize that any benefits conferred from the use of probiotics may be either the direct action of the probiotic or the affect the probiotic has on the existing gut bacteria (4).
A word on probiotics: Probiotics are an extraordinarily large topic with numerous variables, including the strain of bacteria, dosage, condition being treated, and duration of treatment. As much of this is beyond the scope of this post, this is not an exhaustive list of benefits nor research. Many of the benefits are specific to the strain of the bacteria and are still not well understood. I have only covered some of the large amount of studies done involving probiotics. Disease specific research in humans is beneficial in understanding the benefits of probiotics; at this point much of the research shows promise while other research is mixed. Again, this is due to the variables listed earlier. The use of probiotics is becoming more and more common as a daily supplement and I believe as time and research progresses many more benefits of probiotics will come to fruition. Personally, I take a probiotic supplement daily.
Diet is a major contributor to gut health and function because of the microbiome. READ THIS POST on how diet affects gut bacteria and why consistent healthy eating is more important than a detox!
Much of what researchers know about the immune system-gut bacteria relationship is based on responses in mice. The exact cause and effect relationship of an unbalanced gut microbiota and immune system dysfunction still needs to be determined. Because each bacterial strain performs a specific action in regards to immunity, the amount of data to be collected is vast and complex; the human gut microbiota consists of hundreds of thousands of organism. However, we know for sure that the gut microbiota are beautifully interwoven into the immune system and together they help create and sustain life. They were created to function together in an interdependent relationship. Without our immune system, we would not be around very long, and as it turns out our little bacteria friends living in our gut are far more helpful than we ever could have imagined. This is a very exciting area of research, and I look forward to reading more about what researchers discover!
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- The role of the gut microbiota in immune homeostasis and autoimmunity
- Microbiota and autoimmunity
- The gut microbiome shapes intestinal immune responses in health and disease
- Health beneficial acts of probiotics: its mode of action
- Probiotic use in allergic disorders
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