The Gut-Immune Axis
We often discuss the relationship between digestive and cognitive health by virtue of the gut-brain axis. We know that the state of our digestive system is reflected in our mental performance, moods, and emotions. But did you know that there is also such a thing as the gut-immune axis? This means that a healthy gut supports strong immunity.
The intestinal microbiota is comprised of trillions of microorganisms including bacteria, viruses, and fungi. Yet interestingly, what happens in the gastrointestinal tract also has a lot to do with how strong our immune system is against pathogens including, you probably guessed it, bacteria, viruses, and fungi! This immune system-microbiota alliance is due to the evolution of our innate immune system to maintain the mutually-beneficial relationship of the host and the microbes. The disruption of this relationship increases the risk of infection, disturbs the natural inflammatory response, and promotes the overgrowth of harmful microorganisms.
So how does the gut help protect us from diseases?
Considering its length and size, some refer to the gut as the largest immune organ. Since it is regularly interacting with external agents, it is considered one of the most important points of defense against harmful substances and diseases. The microbiome and the gastrointestinal system as a whole supports innate (the built-in defense) and adaptive (the immunity that changes and adapts based on exposure) immune system. A healthy gut supports strong immunity through the following mechanisms:
- Provision of energy and nutrients for the host
- Direct killing of pathogens
- Supporting the host’s protective immune responses
- Facilitating a healthy inflammatory response
- Producing metabolites such as the bile acids
The Gut Helps Provide Nutrition
The primary purpose of the GI tract is the provision of nutrients for energy and physiological function. As the center of digestion, the gut is where food is broken down into usable components for assimilation to the rest of the body.
The gut microbiota’s contribution to the digestive process is the fermentation of non-digestible components like dietary fibers and intestinal mucus. The short-chain fatty acids produced from fermentation like acetate, butyrate, and propionate then play a crucial role in glucose and energy homeostasis. This is why the type and abundance of certain microbes in the gut are also implicated in obesity and metabolic complications.
The Gut Microbiota Helps Eliminate Pathogens
Imagine your gut as a closely-knit community, and pathogens are strangers trying to infiltrate and take-over their territory. Do you think the “resident symbiotes” would just give up their space that easily? They will surely put up a fight. This phenomenon is called colonization resistance, or microbial barrier. Depending on the specific makeup of the gut microbiome, it can help protect the host intestine from external pathogens by forming a protective layer of defense or by directly killing harmful bacteria or viruses.
The Gut Supports the Host’s Protective Immune Responses
Symbiotic microbes present in the gut may help enhance both natural and adaptive immune responses. This is especially important and evident during infancy and early development. The gut microbiota is also critical for the production of antibodies such as the following:
- IgA – This is the most abundant type of antibodies. IgA is the antibody in mucosal secretions in the lungs and intestines that act as an important first line of defense. It is also a blood-born or serum antibody.
- IgE – These antibodies play a critical role in allergies, asthma, and immunity to parasites.
- IgG – The presence of these antibodies indicates that the battle has been over for some time but they remain for future protection.
- IgM – The first responders, so to speak, when reacting to an invasion of a foreign pathogen. They hold the fort while more specific fighters are being launched.
Apart from the microbiota, the lamina propria and gut-associated structures found along the GI tract are also home to the mucosal immune system. This provides additional protective immunity to a multitude of microbial threats.
A Healthy Gut Facilitates a Healthy Inflammatory Response
Gut microbes directly modulate intestinal and systemic immune balance, prompting inflammation to combat pathogens, if necessary. However, certain conditions such as the alteration of microbial communities (also known as gut dysbiosis or leaky gut) may lead to systemic and chronic inflammation that can affect the whole GI system, the central nervous system, or other peripheral organs. Over time, this may cause immune dysregulation, leading to autoimmune disorders.
Leaky gut, or the loss of intestinal barrier integrity to gut microbes, can activate immune cells to release pro-inflammatory cytokines IL-1β, IL-6, TNFα into the circulatory system. The intestinal microbiota also maintains the intestinal barrier through the production of short-chain fatty acids that serve as a primary nutrient for the tissues in the colon. These fatty acids also maintain the thickness of the mucus barrier in the gut.
The Relationship between Microbiota, Bile Acids, and Immunity
Bile acids are signaling molecules that regulate key functions in the human body. They form a crucial component of the bile produced from cholesterol in the liver that further metabolizes them by the gut microbiota into secondary bile acids. The host microbiome, therefore, can regulate bile pool size necessary for digestion, metabolism, and immune homeostasis.
In the same way that gut microbiota is needed in the synthesis of bile acids, bile acids are also able to regulate and modify gut microbial composition since their amphipathic nature is toxic for bacterial cells.
Aside from directly fighting pathogens in the gut, bile acids and bile salts (the conjugated forms) help boost immunity by:
- promoting nutrient absorption in the intestines
- restricting bacterial overgrowth
- acting as hormones that regulate nutrient metabolism via activation of certain receptors
- helping maintain intestinal barrier function
- balancing blood sugar
- managing cholesterol balance
Reduced bile acid levels in the gut are associated with bacterial overgrowth and inflammation. Healthy bile is a prerequisite to a healthy gut, which supports strong immunity.
How do we protect the gut and preserve these immune-boosting functions?
Factors that can affect the balance of the microbiome-bile acid pool include:
Although we do not have control over our age, we can still do a lot to make sure that our intestinal barrier is intact, that our bile salt and bile acid concentration is sufficient, and that we have more “good bacteria” in our gut population. Diet gives us a major advantage.
- Include a large amount and a diversity of vegetables in your diet. Different gut bacteria need different kinds of fiber and more variation in vegetable choices is more likely to satisfy that need.
- Cut out sugar which causes inflammation and tips the balance of the microbes in the gut to an overabundance of the negative type. This includes refined carbohydrates such as bread or pasta.
- Eating allergens trigger inflammation in the gut and all over the body. Continuously eating the wrong things may contribute to leaky gut. On the other hand, natural anti-inflammatory foods can help keep inflammation at bay. Examples are:
- fatty fish such as salmon, mackerel, and tuna
- fruits like avocadoes, blueberries, and strawberries
- vegetables like broccoli, carrots, kale, and spinach
Do not overuse antibiotics
- When we use antibiotics, we do not only kill the pathogen that invades us but also the microbial symbionts that have been contributing to our gut health. It is imperative to use antibiotics only when it is extremely necessary.
Probiotics are live microbial feed supplements which beneficially affect the host by improving microbial balance. These come in many varieties and are available as supplements or through natural food sources.
- Examples of natural probiotic food sources are:
The fiber in vegetables and fruits are prebiotics, or food for those probiotics to thrive, which is why they are so important.
- Examples of natural prebiotic food sources are:
- Jerusalem artichoke
- Dandelion and other leafy greens
Take bile salt supplements
- Perfectly healthy individuals can produce all the bile salts and bile acids that they need for bodily functions. However, in some individuals with liver and gallbladder diseases, bacterial overgrowth, acid hypersecretion, ileal resection, or other related gastrointestinal conditions, bile salt concentrations in the intestine can fall to less than the critical concentration. This may lead to impaired micelle formation, fat malabsorption, indigestion, and disrupted gut microbiota. Taking bile salt supplements during meals may support a healthy bile acid pool and a more balanced gut microbiome.
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