What is the Gut-Immune Connection?

The human gastrointestinal (GI) tract is lined with upwards of a hundred trillion resident microorganisms, including bacteria, fungi, protozoa, and viruses, collectively referred to as microbiota. (29)(32) This microbial community has been found to work closely with the immune system and contribute to metabolic health. (12) Research indicates that a dysfunctional gut microbiota is associated with an increased risk for infection as well as the development of certain autoimmune (e.g., Crohn’s disease, ulcerative colitis) and atopic (e.g., allergies, eczema) conditions. (2)(27)

The gut and the immune system

Humans and microorganisms have been interdependent for billions of years. (11) The human immune system has evolved with microorganisms, adopting a commensal (beneficial) relationship with microbiota. (16) Microbiota can produce metabolites (substances that are broken down and then used by the body) to be used for energy, maintain health, and remove toxins. (10)(22)(34) These metabolites play an important role in the development and function of the immune system. Due to the body’s reliance on the microbiota for these vital substances, a person’s health may be influenced by the health of their microbiota. While microbial communities can be found all over the body, over 70% of human resident microorganisms are contained in the GI tract. (27)

Innate immunity

The innate, or non-specific, immune system is our body’s first line of defense against antigens (immune-stimulating substances). Antigens are typically proteins on the surface of cells or microorganisms, but they can also be chemicals, toxins, and foreign substances. (24) Body cells and commensal microbes may also carry antigens, so the immune system has evolved dynamic mechanisms to distinguish between friend or foe. (19)(24)

Germ-free animal studies, in which subjects are raised without exposure to microbes, have demonstrated that the development of the innate immune system is closely linked with microbiota. Germ-free animals consistently exhibit an underdevelopment of immune tissues within the gut and reduced numbers of certain immune cells. (11) In mice, the absence of microbiota was found to make them more susceptible to infections and less efficient at absorbing nutrients. (14)(33)

Gut microbiota may also play a role in the development of immune tolerance, as gut microbiota of infants with allergies was found to carry less of certain beneficial bacteria. (25) According to germ-free animal studies, introducing bacteria to the gut can restore some abnormalities and help to rejuvenate immune strength, further demonstrating the link between the bacteria in the gut and the immune system. (13)

Mucosal immunity

Due to its constant exposure to antigens, more than half of the body’s antibody-producing cells are found in the gut wall. (17) Lined with a protective mucus layer, the gut wall is armored with the mucosal immune system, a network of immune cells, immune organs, and cell receptors that work collectively to provide a protective barrier from antigens. (28)

In the gut, the mucosal immune system relies on a thriving microbiota in order to support its function. The gut microbiota support mucosal immunity by:

• Colonizing the intestinal lining
• Limiting nutrients available to pathogens (8)
• Producing antimicrobial substances
• Supporting the GI tract’s protective mucus layer (4)

Gut microbiota use their collective genome (microbiome) to facilitate various metabolic reactions that support the integrity of the mucosal immune system. The microbiome breaks down (ferments) non-digestible substances, such as dietary fiber, and produces metabolites, such as essential amino acids, vitamins, and short-chain fatty acids (SCFAs). (29)(31)(34) SCFAs are almost exclusively produced by gut bacteria and play an important role in the overall maintenance of health and disease prevention. (31) SCFAs have been shown to activate and regulate certain immune cells, stimulating cell migration and repressing proinflammatory molecules. (18) SCFAs also support mucosal immunity, as they are the main energy source for colon cells and regulate the strength of the mucosal barrier. (36)

What factors affect the gut and immune health?

The gut microbiome may be influenced by multiple factors including:

• Activity level
• Age
• Alcohol use
• Diet composition
• Genetics
• Geography
• Medication use (e.g., antibiotics, NSAIDs)
• Method of infant delivery and feeding
• Stress
• Tobacco use (3)(9)

Failing to foster good gut health can negatively impact immune function. Poor gut health can lead to bacterial dysbiosis, a significant bacterial shift that allows invasive and proinflammatory bacteria to dominate the microbiome. (2) Research indicates that the health of microbiota may influence the progression of conditions both within the gut and outside the GI tract, including:

• Atherosclerosis
• Autoimmune conditions (e.g., type 1 diabetes)
• Atopic conditions (e.g., allergies, asthma, eczema)
• Inflammatory conditions (e.g., irritable bowel syndrome, pancreatitis)
• Obesity
• Type 2 diabetes (27)

Reports indicate that an inflamed gut is related to weakened immune tolerance. (4)

How to support a healthy gut

A healthy microbiome looks different for everyone, as no two people have the same microbiota composition within the gut. (15) Certain microbial distributions may increase disease risk, so a widely diverse microbiota is one of the main indicators used to assess microbiota health. (1) Similar to overall health, gut health can be supported by a balanced diet, exercise, and healthy weight.

Consume a balanced diet

The main contributor to gut health is diet. Over 60 tonnes of food pass through the human GI tract during the human lifetime. (32) The process of digestion and fermentation in the gut is critical for human health, microdiversity of the gut, and overall immune function. (8) Dietary changes can affect gut health within as little as 24 hours. (29) Whole food diets, such as the Mediterranean diet, are related to a healthy gut, while the Standard American Diet (SAD), commonly known as the Western diet, is associated with dysbiosis. (30)

In general, the Western diet is high in animal protein and saturated fats and low in dietary fiber. This leads to a decrease in beneficial bacteria, making more room for pathogens. A fiber-rich, whole food diet that includes fruit, vegetables, legumes, whole grains, fish, and low-fat dairy products has been found to reduce inflammation and support the production of SCFAs. Simultaneously, a balanced diet provides essential minerals and nutrients that support the function of immune cells. (30)

Following the Dietary Guidelines for Americans can help support a healthy diet.

Maintain a healthy weight

The combination of excess energy intake and a sedentary lifestyle has led to a rise in obesity rates. (26) Obesity is characterized by the enlargement of adipocytes (fat storage cells) due to excess energy storage. Research in mice suggests that obesity, regardless of diet, can trigger microbial dysbiosis, which has been found to contribute to increased inflammation and chronic disease risk. (21)

In mice with obesity, the microbiome displayed an increase of genes associated with the fermentation of carbohydrates. Compared to lean mice, these genes were associated with increased energy extraction and fat deposition. Transplanting microbiota from obese mice to germ-free mice was found to significantly increase body fat relative to germ-free mice that were colonized with microbiota from lean mice, suggesting that the gut microbiome may contribute to the development of obesity. (27) The dysbiotic microbiome of obese mice was also found to weaken the mucosal lining of the GI tract, triggering inflammation and allowing potential pathogens into the blood stream. (5)(21)

Engage in regular physical activity

Regular physical activity can support gut and immune health, promote weight management, and reduce obesity-induced inflammation. (7)(26) Compared to healthy and overweight males, the gut microbiome of professional athletes was found to be more diverse, and circulating inflammatory markers were significantly less. (7) The Centers for Disease Control and Prevention (CDC) recommend 150 minutes of moderate-intensity activity per week, which is just 30 minutes per day five days a week. (6) Biking, dancing, and swimming are just a few examples of moderate-intensity activity. If you’re a patient, check with your integrative practitioner before beginning a new exercise regimen.

Consider probiotics

Probiotics are defined as live organisms that, when administered at appropriate doses, are beneficial to the host. (35) Probiotics can come from dietary sources, including fermented foods such as yogurt and kimchi, as well as dietary supplements. Probiotics have been found to improve a variety of atopic and inflammatory conditions, as well as strengthen the mucosal immune system. (20) Many details, including the probiotic strains or combinations, doses, and populations that may significantly benefit, are largely unknown, indicating that more research is needed to fully understand the potential benefits of probiotics. (23)

The bottom line

Gut microbiota contribute to gut health as well as overall health. Working closely with the immune system, research indicates that a dysfunctional microbiome can increase the risk for infection and contribute to the development of chronic diseases, including obesity and type 2 diabetes. Consuming a balanced diet rich in fiber, engaging in regular exercise, and maintaining a healthy weight are some modifiable factors that can significantly impact the health of the microbiome.