Did you know that 80% of your immune system is in your gut? This might not be so obvious until you consider the fact that the GI tract is technically considered as being outside of your body, and provides a permeable barrier protecting the inside of the body from the external environment. This selective permeability depends on the tight junctions between the epithelial cells that prevent large pathogenic molecules from passing through, and allows for bidirectional communication with the native bacteria. This all takes place in the small and large intestines and is considered the first line of defense against exogenous foreign substances such as food antigens (allergens), pathogens, and even local / commensal microorganisms, which can become pathogenic (pathobiont). This system of defense is possible only through a complex coalition between the gut flora, mucosal immune cells, and the intestinal epithelial barrier, which together constitute the innate immune system.
In order for this system to function, each of these components must work in unison with one another so the immune system can do its job and identify and neutralize threats to our health. As mentioned before, a balanced microbial community is necessary for optimal health, and now we’ll see exactly why it’s such an important player in the regulation and activation of the immune system. Here are a few of the microbiome’s functions:
Direct interactions One way our partners (microbiota) help protect us is by direct interaction with pathogens to prevent them from intruding. They’re able to accomplish this in various ways. 1) They produce toxins that inhibit the same or similar bacterial species from colonizing the same area in the intestine. 2) Commensal bacteria can also alter the microenvironment by changing the pH, which makes the intestines inhospitable to invading pathogens, thereby decreasing the chances of infection. 3) Commensal bacteria can starve out the pathogenic bacteria by consuming the limited amount of nutrients needed for their growth. 4) Native bacteria can also produce metabolites that downregulate pathogenic virulence and prohibit any further growth.[i]
Indirect Interactions Microbiota can indirectly prevent pathogenic occupation and infection by promoting epithelial barrier function. The epithelial structures of the gastrointestinal lining are the primary barrier that protects us from harm, in other words, the first line of defense. The mucosal immune system resides here, and according to research, a bidirectional “crosstalk” takes place between the microbiome and the immune system via signal monitoring. Signals from the metabolic activity of resident bacteria are monitored by immune cells, which are then modified to prevent infections and the further proliferation of pathogens by supporting the integrity of the tight junctions within the intestinal epithelium.[ii]
Managing Inflammation Inflammation is present in all chronic diseases, but most particularly in those directly related to the gut like; ulcerative colitis, small intestine bacterial overgrowth (SIBO), Crohn’s and Celiac disease, and obesity. As more data accumulates on the Pathomechanism of these diseases, and as we learn more about the hidden world of our gut flora it’s becoming more obvious how big of a role the microbiota play in the pathogenesis of these diseases. For instance, a recent Dutch study examined the fecal microbiota of 28 individuals that were segregated into two groups, obese and non-obese. They found that the obese group lacked bacterial diversity, and the bacterial strains were of a pro-inflammatory nature compared to the non-obese group.[i] - keep in mind that adiposity is a state of chronic inflammation. An older study was able to show that there is a microbial component to obesity, which manifests in a decreased ratio of Bacteroidetes to Firmicutes, both of which are beneficial bacteria found in the human gut.[ii] In the case of IBD (includes UC and Crohn’s) patients, there is a recurring theme in many of the animal and human studies that highlight a lack of microbial diversity, which compounds other etiological factors such as; diet, environmental factors , genetics, stress, and enteric infections caused by pathogens.[iii] Another common feature among IBD patients is that their GI tract seems to be suspended in a pro-inflammatory state caused by an overproduction of helper T cells (inflammation- mediating) compared to anti-inflammatory regulatory T cells.[iv]
One apparatus used to manage inflammation is microbe – induced regulatory B and T cells (immune cells), which operate within both the innate and adaptive immune systems. When the gut flora is imbalanced these cells are not able to respond to threats that may cause systemic inflammation or tissue damage.[v]
Short chain fatty acids (SCFAs) are metabolic end products produced by the bacteria through a process of fermentation of macronutrients. These stimulate the production of helper T cells, which also support intestinal epithelial barrier permeability.[vi]
Effects on the Adaptive Immune System The adaptive immune system is the second line of defense in our immune system. It’s activated when the innate immune system is not able to eliminate entirely the pathogenic threat to the host. Unlike the innate immune system, the adaptive immune system has a working memory of past encounters with pathogens, which allows faster recognition of some pathogens.
Resident bacteria play a key role in the differentiation and activation of B cells, which secrete an antibody known as IgA when there is a food antigen present.[i] The importance of the microbiota in the production of B lymphocytes was shown in a study using germ free mice that lacked intestinal flora. These mice had reduced levels of B lymphocytes and low levels of circulating IgA. The mice were then colonized with a particular strain of bacterium, which led to an increased production of lymphocytes and increased levels of IgA.[ii] The final conclusion validating that without the right mix of microorganisms in the GI tract will lead to deregulation of this aspect of the immune system.
The beneficial bacteria that populate the colon produce a substance called peptidoglycan, which is a major structural component of bacterial cell walls. This is released into circulation where it’s recognized by specialized receptors that stimulate distant immune effector cells (ie. neutrophils, mast cells), to translocate to sites of infection, inflammation[iii] and allergens.[iv] This can also occur within the innate immune system in relation to inflammatory bowel disease and autoimmune disease.
This was a very brief synopsis of an extremely new and complex field of medicine that is quickly rendering new data, which is illuminating the answers to old questions. The takeaway from this is the realization that, not only are your lifestyle choices important for the perpetuation of your health and longevity, but so is the proper custodianship of your microbial ecosystem. Paying more attention to and maintaining your gut health has global repercussions in the pathogenesis of disease, all within the framework of GI immunity, which encompasses the innate & adaptive immune systems, the intestinal epithelial barrier and the microbiota, who in a sense, run the show.
Final note: If you would like to participate in a national scientific research project that seeks to explore the microbial diversity of the human gut, you can order a kit for as little as $99. You send the researchers a sample and they give you a report of findings. This is a great way to participate in an open – source science project, while expanding the knowledge base of our microbiome and the differences between regions and individuals. Here’s the link: American Gut
Check back with us next week as we explore some of the diseases associated with imbalanced gut flora such as: SIBO, IBD, Rheumatoid arthritis, obesity, metabolic disorders, etc. We’ll also be looking at the gut – brain axis and how the microbiota can affect a person’s mood.
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