Longevity Articles

How the Microbiome Affects the Immune System

The trillions of bacteria in the intestinal tract make up the gut microbiome.

The microbiome is the collection of bacteria that reside in our intestinal tract, to the tune of almost 40 trillion bacterial cells in the average human gut. Once thought to just play a role in digestion and the synthesis of certain vitamins, research has exploded recently on the various areas in which our gut microbes influence our health. From modulating mood disorders to inflammation to the immune system, our microbiome does much more in the body than we knew just a few years ago. If you’re looking to improve your healthspan, here’s what you need to know about this amazing micro-ecosystem in the body. 

What is The Microbiome?

Also known as the gut microbiota, the makeup of bacteria in our gastrointestinal tracts varies from person to person. Each individual’s microbiome starts to form at birth and is altered by genetics, dietary and lifestyle habits, environmental conditions, age, and medications. It can even change based on which people — and animals — you share your home with. 

A major mechanism by which the microbiome affects human health is through the production of short-chain fatty acids (butyrate, acetate, and propionate), which are created when dietary fiber is fermented in the gut. These fatty acids play an important role in reducing inflammation, protecting the intestinal lining, as well as keeping the microbiome diverse by being a food source for healthy bacteria to thrive on.

The Gut-Immune Relationship

The complexity of the immune system is made even more intricate by its relationship with the microbiome. As 70% to 80% of the body’s immune cells can be found in the gut, it has become more and more apparent that the function of our microbiome plays a direct role in the function of our immune system.

As one of the main priorities of our immune system is to keep foreign pathogens out, it may be surprising that we allow for so many trillions of bacteria to live inside of us. However, the relationship between the microbiome and the immune system has always been coevolving; they have a mutualistic interaction in which both systems regulate and support the other to keep the good bacteria in and the bad bacteria out.

The intestinal wall, which is the primary separation between the intestinal tract and the rest of the body, is made up of a single layer of epithelial cells and the mucus they produce. This creates a physical barrier that prevents bacteria from translocating from the gut into the bloodstream. 

The Innate Versus Adaptive Immune Response

There are two types of responses that the immune system employs: the innate and the adaptive. Briefly, the innate response is non-specific and is the first line of defense against pathogens to eliminate foreign threats quickly. This method could use physical, chemical, or cellular defenses to immediately prevent the spread of the pathogen throughout the body.

The adaptive immune response is the second line of defense and is more complex and specific, meaning it has a memory of previous threats. Cells called lymphocytes are the main players, which are primarily B cells and T cells. 

B cells work by recognizing foreign antigens and producing antibodies to target and eliminate that pathogen. The T cells are involved in cell-mediated immunity, which activates other immune cells like cytokines and phagocytes to kill pathogens. 

The microbiome and the immune system have a mutualistic relationship that involves many different cells and bacteria.

The microbiome is involved in the adaptive immune system, as both T and B cells are located in the gut-associated lymphoid tissue (GALT) of the intestinal walls. These cells act as microbial sensors by suppressing any overreactions to harmless bacteria while recruiting other immune cells to the gut if a harmful microbe is present. 

Although there are dozens of molecules involved in the complex interactions between the immune system and the microbiome, one called secretory immunoglobulin A (SIgA) may be the most important. 

SIgA is an antibody that serves as the first line of defense against intestinal pathogens by entrapping the foreign invaders in mucus and clearing them from the body. SIgA promotes a diverse and balanced microbiome, and the presence of certain bacteria in the microbiome can also increase the production of SIgA.

The bacteria in our gut also enhance the adaptive immune response through inducing T cell differentiation. Naive T cells can modify themselves into several different types of mature T cells, including natural killer cells and T helper cells, such as Th1, Th2, and regulatory T cells (T-regs). 

For example, the bacteria Bacteroides fragilis induces the differentiation into T-reg cells, which prevent the overactivation of the immune system that is seen with autoimmune diseases. 

When you have a microbiome that isn’t healthy and balanced — also known as dysbiosis — the gut lining becomes weak and permeable. Sometimes referred to as “leaky gut,” an increase in intestinal permeability means that undesired compounds, such as pathogens, can make their way from the gut into the bloodstream. This permeable gut lining can cause a whole host of health issues, ranging from asthma to autoimmunity to allergic responses to food. 

Do Probiotics Boost the Immune System?

In times when we want to ensure that our immune systems are functioning as well as they can, you may be wondering if taking a probiotic supplement can help to fight off illness. Probiotics, meaning “for life,” are friendly bacteria that benefit the host in some way. Although there are trillions of bacteria in the gut, most probiotics that we consume come from the genus Lactobacillus, Bifidobacterium, Enterococcus, Streptococcus, Bacillus, or the yeast Saccharomyces.

As the bacteria in our guts are constantly competing with one another for space, adding probiotics to your diet or supplement regimen can work well to crowd out the pathogenic and harmful bacteria.

A November 2017 meta-analysis published in Nutrients pooled data from nine randomized controlled trials and found that people who took probiotic supplements had better immune responses after inoculation with influenza vaccines. In other words, probiotics made the flu shot more effective and protective. 

In a clinical trial published in Nutrients in June 2017, individuals who consumed probiotic-containing yogurt for 12 weeks had increases in several beneficial immune cells, including natural killer cells and interleukin-12, which is a cytokine that has a protective effect on the immune system.

Lastly, in a study published in BMJ in June 2001, children who were randomized to receive probiotic-containing milk with Lactobacillus GG had reductions in both the prevalence and severity of respiratory infections, compared to those who received the placebo.

How to Support Your Microbiome

Support the diversity in the microbiome by consuming probiotic and prebiotic, or fibrous, foods.

There are several ways to ensure that your gut microbiome is thriving with healthy and diverse bacteria: 

  • Eat foods that naturally contain probiotics, like fermented vegetables, sauerkraut, kimchi, yogurt, or kefir. 
  • Consume foods that are high in prebiotics, which are fibrous compounds that the probiotics can feed on to stay alive in the gut. Prebiotic-rich foods include onions, garlic, apples, leeks, and less-ripe bananas. 
  • Take a high-quality probiotic supplement that contains at least 1 billion CFU (colony-forming units) of healthy bacteria per capsule.
  • Limit added sugar and refined carbohydrates, which do not contain the fiber that your gut microbes need to survive. (Take a cue from those living in The Blue Zones.)

Key Takeaways:

  • The microbiome and the immune system have a complex and mutualistic relationship, as both rely on the other to fight foreign pathogens, and 70-80% of the body’s immune cells can be found in the gut.
  • Studies have shown that certain probiotics (healthy bacteria) can reduce the risk of getting sick through the enhancement of immune cells.
  • The microbiome is best supported through the consumption of prebiotic and probiotic foods or combined with a high-quality probiotic supplement.
  • Combine the above tips with a good night’s sleep and exercise, and you’ll be well on your way to cultivating your microbiome health. 


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Zhang CX, Wang HY, Chen TX. Interactions between Intestinal Microflora/Probiotics and the Immune System. Biomed Res Int. 2019;2019:6764919. doi:10.1155/2019/6764919

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