The Gut-Immune Connection: The Role of the Gut Microbiome in Your Immunity

The gut is home to trillions of microbes that collectively comprise your gut microbiome (the largest and most diverse microbiome of the body).¹ The gut microbiome is most often associated with digestion and gastrointestinal health, though this expansive ecosystem is essential for so much more—including the immune response.

Here’s what to know about how your resident gut microbes impact the function of your immune system via the gut-immune axis, or gut-immune connection.

What Is The Immune System?

The immune system is a vast network of cells, proteins, and organs that fight harmful substances that come into contact with the body (i.e., pathogenic bacteria) or disease-causing changes that occur within the body (i.e., damaged cells).² 

It’s activated by substances the body doesn’t recognize as its own, called antigens. When the immune system is functioning properly, it recognizes, identifies, and neutralizes antigens, so they go unnoticed by you. But if it becomes weak or unable to fend off certain threats, that’s when you can get sick. 

When an antigen attacks the body, two separate, yet interrelated, branches of the immune system are activated: the innate immune system and the adaptive immune system. While each system has its own distinct mechanisms, they both work together to combat foreign materials to protect the body from illness. 

• Innate immune system: The innate immune system is the first response to foreign substances, and it defends against outside pathogens trying to enter the body. This system is responsible for generalized immune responses like inflammation and fevers, and defense mechanisms like saliva and tears. It also includes physical barriers like the skin and gastrointestinal tract. Like the skin, the gastrointestinal tract provides a protective barrier between the bloodstream and external inputs (food, liquids, air), regulating what can pass through the gut wall. 
• Adaptive immune system: The adaptive immune system, or acquired immunity, targets specific pathogens that your body has already encountered, mounting a more specialized attack. Because the adaptive immune system can learn and remember specific antigens it’s been exposed to in the past, it provides long-lasting immunity against recurrent infections. While we are born with innate immunity, our adaptive immunity develops over time. This is part of the reason that children tend to get sick more often than adults.³

So, how does the immune system learn to perform all of its critical functions—and what’s your gut got to do with it? 

How Your Immune System Develops

Microbes help develop and train the immune system, and they get to work before we’re even born.

In utero, metabolites produced by maternal microbes, maternal immune cells, and antibodies help prepare the prenatal immune system, ensuring a newborn is able to mount an immune response directly after birth.⁴ Though the presence of a prenatal microbiome is still debated, some preliminary evidence in animal models suggests select microbes may actually “seed” and colonize the fetus before birth, contributing to immune and microbiome development.  

After birth, the immune system continues to develop in coordination with a newborn’s microbiome. Resident microbes help train the immune system to distinguish between benign substances (i.e., the body’s own cells, outdoor particles like pollen) and pathogenic antigens (i.e., infectious microbes). This is also when the immune system learns how to “immunoregulate,” or appropriately coordinate an inflammatory response to stressors and infections. 

Factors like diet, antibiotic use, and environmental exposure all shape a newborn’s microbiome and affect the development of the immune system during this crucial time. Disruptions to these early microbial interactions can have long-term effects on immune system function. 

For example, if the immune system has trouble determining what is self versus non-self, it may attack the body’s own cells (known as autoimmunity) or over-respond to harmless antigens, causing food or pollen allergies. 

The Gut Microbiome’s Role in Immunity

The relationship between microbes and the immune system doesn’t end after childhood. As we age, there continues to be plenty of cross-communication between intestinal microbiota and immune receptors and cells. 

For example, gut microbes break down proteins and carbohydrates within the body, synthesize vitamins, and produce a range of other metabolic products known as metabolites that can facilitate communication between gut cells and immune cells.⁵

The gut microbiome also regulates and fine-tunes the immune system, inducing protective reactions to pathogens and maintaining proper immune responses within the body. Gut microbes protect you from external factors through various tactics.³ They:

• Help control inflammation and mediate the inflammatory immune response: This helps your immune system respond to inputs during appropriate times (e.g., when stimulated by a foreign antigen) while remaining passive to inputs that don’t pose a threat (e.g., food or pollen).⁶
• Strengthen gut barrier integrity: Gut microbes support the presence of tight junctions (intercellular connectors that form the main scaffolding of the gut barrier, preventing foreign materials and contaminants from crossing it). Disruptions in the intestinal barrier structure can trigger local immune reactions and allow unwanted microbes to grow.⁷
• Compete with potential pathogens for resources: ​​If your commensal (resident, non-harmful) microbiota utilize all of the available resources in the gut, such as space and nutrients, pathogens can’t survive.⁸
• Produce antimicrobial substances: Certain commensal bacteria in the gut produce bacteriocins—proteins that inhibit or kill pathogenic bacteria such as Listeria, Clostridium, and Salmonella.⁹

To carry out these protective functions, your gut microbiome needs to be populated primarily by beneficial microbes, with a low presence of microbial species typically characterized as “harmful.” 

When the gut microbiome is disrupted—which can arise from infection, inflammation, immune deficiency, sleep pattern, changes in diet, or exposure to antibiotics or toxins—it can shift in composition, causing uncontrolled or heightened immune responses. (This is why you might be more prone to getting sick after an indulgent vacation or particularly stressful period at work.)

Dysbiosis (an imbalance in microbial composition) in the gut triggers pro-inflammatory effects in the body.¹⁰ It’s been linked to immune dysregulation (a breakdown in the control of immune system processes), inflammatory bowel disease (IBD), Type 1 Diabetes, food allergies, asthma, neurodegenerative disorders, and even obesity.^11,12,13,14 

In short, if you want to protect yourself against pathogens and combat chronic disease (and who doesn’t?), supporting your gut-immune axis is essential. 

4 Ways to Support Your Gut-Immune Axis

Your diet, exercise, sleep quality, stress, and surroundings can all shape the structure and function of your microbiome (and by extension, your immune system) throughout life. Here are four science-derived strategies to foster a healthy gut-immune connection: 

1. Increase your fiber intake.

The fiber in fruits, vegetables, legumes, nuts, seeds, and whole grains is fermented by gut microbes and transformed into short-chain fatty acids (SCFAs) in the digestive tract. These SCFAs then interact with immune cells and regulate anti-inflammatory and antioxidant responses to help defend against pathogens and certain autoimmune conditions.^15,16,17 

2. Prioritize sleep.

Your brain’s hypothalamus operates on a 24-hour cycle, known as your circadian rhythm. Emerging data also show that the gut microbiome has its own circadian clock, which dictates the timing of essential processes.¹⁸ Changes to your normal “rhythms” induce what is known as “circadian misalignment,” which may disrupt your microbes and the important functions they perform.

3. Manage stress.

The inflammation that often accompanies high levels of stress triggers blooms of pathogenic microbes in the gut.¹⁹ These promote dysbiosis and increased intestinal permeability (aka leaky gut), paving the way for pathogenic bacteria to invade. 

4. Take a probiotic.

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. Taking specific strains of probiotics have been shown to support a range of benefits within the gastrointestinal system, including the reinforcement of gut-barrier function and the support of cross-talk between gut and immune cells.²⁰ 

Taking these steps is especially important during times when you’re exposed to lots of new germs—be it during the holidays or back-to-school season. 

The Key Insight

The immune system co-evolved with microorganisms, learning to tolerate and even collaborate with the microbes living in and around us. This intrinsic connection between the gut and the immune system contributes to immune homeostasis, immune responses, and protection against pathogens.⁷ 

However, modern living (and its antibiotics, Westernized diets, environmental toxins, and lack of exposure to nature) has disrupted our relationship with microbes, contributing to myriad immune diseases and disorders. As we search for ways to prevent, remediate, and even eradicate these issues, now you know why considering the gut microbiome will be essential.