The Science Behind Allergies and Gut Immunology

What Is the Gut?

The gut is one of the largest organs in the body in terms of surface area and the number of bacterial species that colonize it. The composition of the gut microbiome changes substantially from infancy to adulthood. The microbiome helps the body accommodate and adapt to things coming from the outside.

What Bacteria Live in the Gut?

Four main bacteria live in the gut:

• Actinobacteria
• Bacteroides
• Firmicutes
• Proteobacteria

These bacteria live alongside fungi and viruses. Together, these microbes impact gut immunology.

What Is a Leaky Gut?

Our body generates an immune response by reacting to an antigen, normally a foreign substance. In the upper bowel, most antigen exposure comes from a person’s diet. When someone has a “leaky gut,” antigens cross the epithelial surface (a protective layer of tissue) through breaks in tight junctions of the bowel. A leaky gut results from antibiotics, NSAIDs, and dietary habits. Because of antigens breaking through the body’s barriers, the immune response can become pathologic and influence atopic disease.

Normal Gut Immunology

The gut has an extensive and highly active immune system comprised of many parts:

• Peyer’s Patches: Peyer’s patches in the small bowel are aggregates of lymphoid tissue, organized structures where the immune system plays out its response. An average adult has at least 200 of these. Within each Peyer’s patch, follicle-associated epithelium in the intestinal wall can directly sense pathogens.
• The epithelium: The epithelium has tight junctions that prevent antigens from permeating the gut. The epithelium secretes mucus that traps antigens before they enter the gut lumen. The epithelium itself can also directly sense bacteria and pathogens, even outside of the localized areas of lymphoid tissue. This tissue contains specialized “M Cells” that transport gut bacteria and antigens from the gut lumen into the lymphoid tissue.
• Bacteria: The epithelium has bacteria that live within it. These bacteria help the epithelium maintain integrity by exerting an anti-inflammatory response that protects the epithelium.
• Dendritic cells: Dendritic cells present antigens to other immune cells, such as T-cells and B-cells, which create immune cells that generate an immune response specific to those antigens.
• Macrophages: The gut has special macrophages that are responsible for “eating” and digesting pathogens.
• T-cells and B-cells: T-cells help activate B-cells, which are cells that secrete proteins called antibodies. Antibodies help your body get rid of a pathogen. The main type of antibody produced in the gut is known as IgA.
• Regulatory T-cells: Because the body doesn't want immune cells to damage the gut’s tissues, it utilizes immune cells called regulatory T-cells. These cells release proteins called cytokines. While some cytokines promote inflammation, the cytokines secreted by regulatory T-cells have an anti-inflammatory effect.

Gut Inflammation and Food Allergies

A leaky epithelial barrier can cause excessive activation of antigens, specifically Th2 and regulatory T cells (Tregs). Normally, when food is eaten, there isn’t an immune response because the gut environment is rich in Tregs and short-chain fatty acids. These short-chain fatty acids produce more Treg cells, which protect the intestinal lining from inflammation. One reason gut bacteria is crucial to gut immune function is that it helps produce these short-chain fatty acids.

In early life, gut bacteria strongly correlates with the risk of developing food allergies later in life. This phenomenon occurs because when you lose bacterial flora, you develop more Th2 cells and fewer Treg cells. Th2 cells increase the type of antibody in allergic responses (IgE).

One study compared the first stool of infants and found that those with less rich microbiota were more likely to develop allergies by age one. Furthermore, providing probiotics to infants has been shown to reduce the risk of future atopic disease due to more short-chain, fatty-acid-producing bacteria. Improving children’s gut bacteria has promising implications for the reduction of food allergies.

The Gut-Lung Connection

The understanding of the gut-lung connection came from an observation that different lung diseases were influenced by intestinal microenvironment changes and vice versa. Like with allergies, early life is the most important period where gut imbalance may lead to the development of respiratory illnesses, specifically asthma.

There are many different types of asthma, and each type is associated with different pathophysiology, risks, and symptoms. The type of asthma a patient has is closely linked to the microbiome of the lung, which is also linked to the microbiome of the gut.

What Influences the Microbiome and Allergy?

Below are factors that influence both the microbiome and allergies. These further indicate a relationship between environmental factors and allergies. They also show that the more antigens exposed in early life, the less likely a person will suffer from allergies later.

• Animal exposure
• Family size
• Born first among siblings
• Less antibiotic exposure
• High fiber, fruit, and vegetable diet
• Maternal diet during pregnancy
• Breastfeeding

Can the Gut-Allergy Connection Be Used to Treat Allergies?

Now that science is starting to understand how the gut microbiome affects allergies, scientists are trying to garner this information to treat allergies.

One possible treatment method is to engineer the microbiome so that it has more bacterial strains that produce short-chain fatty acids. Treating patients with regulatory T-cells specific to food allergies could help suppress unnecessary immune responses. Therefore, the GI tract offers great potential as a venue for future allergy treatments.

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