A Healthy Gut Supports Strong Immunity

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 comprises 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 between 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?

Some refer to the gut as the largest immune organ, considering its length and size. Since it regularly interacts with external agents, it is considered one of the most important defense points against harmful substances and diseases. The microbiome and the gastrointestinal system as a whole support the innate (the built-in defense) and adaptive (the immunity that changes and adapts based on exposure) immune system. A healthy gut promotes strong immunity through the following mechanisms:

1. Provision of energy and nutrients for the host
2. Direct killing of pathogens
3. Supporting the host’s protective immune responses
4. Facilitating a healthy inflammatory response
5. 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 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 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 antibody. IgA is the antibody in mucosal secretions in the lungs and intestines that act as an essential 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 Supports Strong Immunity and 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.

A 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 by producing 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 the 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 can also 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 specific 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 in a healthy gut 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:

• Age
• Diet
• Antibiotics
• Disease

Although we do not control our age, we can still do a lot to ensure 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.

1. Change Your Diet

• 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

2. Do not overuse antibiotics.

• When we use antibiotics, we do kill not only 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.

3. Take probiotics

Probiotics are live microbial feed supplements that beneficially affect the host by improving microbial balance. These come in many varieties and are available as supplements or natural food sources.

• Examples of natural probiotic food sources are:
  • Kombucha
  • Kefir
  • Sauerkraut
  • Kimchi

4. Take prebiotics

The fiber in vegetables and fruits are prebiotics, or food for those probiotics to thrive, so they are so important.

• Examples of natural prebiotic food sources are:
  • Jerusalem artichoke
  • Asparagus
  • Garlic
  • Dandelion and other leafy greens

5. Take bile salt supplements

• Perfectly healthy individuals can produce all the bile salts and bile acids needed 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 impair micelle formation, fat malabsorption, indigestion, and disrupted gut microbiota. During meals, taking bile salt supplements may support a healthy bile acid pool and a more balanced gut microbiome.

References:

1. Ridlon, J. M., Kang, D. J., Hylemon, P. B., & Bajaj, J. S. (2014). Bile acids and the gut microbiome. Current opinion in gastroenterology, 30(3), 332.
2. Ramírez-Pérez, O., Cruz-Ramón, V., Chinchilla-López, P., & Méndez-Sánchez, N. (2018). The role of the gut microbiota in bile acid metabolism. Annals of hepatology, 16(1), 21-26.
3. Molinero, N., Ruiz, L., Sanchez, B., Margolles, A., & Delgado, S. (2019). Intestinal Bacteria interplay with bile and cholesterol metabolism: implications on host physiology. Frontiers in physiology, 10, 185.
4. Wu, H. J., & Wu, E. (2012). The role of gut microbiota in immune homeostasis and autoimmunity. Gut microbes, 3(1), 4-14.
5. Fung, T. C. (2019). The microbiota-immune axis as a central mediator of gut-brain communication. Neurobiology of Disease, 104714.
6. Ridlon, J. M., Harris, S. C., Bhowmik, S., Kang, D. J., & Hylemon, P. B. (2016). Consequences of bile salt biotransformations by intestinal bacteria. Gut microbes, 7(1), 22-39.
7. Semrad, C. E. (2012). Approach to the patient with diarrhea and malabsorption. Goldman’s Cecil Medicine, 895.
8. Pitt, H. A., & Nakeeb, A. (2016). Bile secretion and pathophysiology of biliary tract obstruction. In Blumgart’s Surgery of the Liver, Biliary Tract and Pancreas: Sixth Edition (pp. 123-132). Elsevier Inc..
9. Pickard, J. M., Zeng, M. Y., Caruso, R., & Núñez, G. (2017). Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease. Immunological reviews, 279(1), 70-89.
10. Rolhion, N., & Chassaing, B. (2016). When pathogenic bacteria meet the intestinal microbiota. Philosophical Transactions of the Royal Society B: Biological Sciences, 371(1707), 20150504.
11. Kigerl, K. A., Zane, K., Adams, K., Sullivan, M. B., & Popovich, P. G. (2020). The spinal cord-gut-immune axis as a master regulator of health and neurological function after spinal cord injury. Experimental neurology, 323, 113085.
12. Belkaid, Y., & Hand, T. W. (2014). Role of the microbiota in immunity and inflammation. Cell, 157(1), 121-141.
13. Valdes, A. M., Walter, J., Segal, E., & Spector, T. D. (2018). Role of the gut microbiota in nutrition and health. Bmj, 361, k2179.
14. Kechagia, M., Basoulis, D., Konstantopoulou, S., Dimitriadi, D., Gyftopoulou, K., Skarmoutsou, N., & Fakiri, E. M. (2013). Health benefits of probiotics: a review. ISRN nutrition, 2013.