Immune Health and the Gut

by Dr. William J. Keller

If you have done some reading on the immune system lately, you know that immunity involves a complex network of specialized cells and organs that evolved to defend the body against attacks by foreign invaders such as bacteria, viruses, fungi and other parasites.

The two basic kinds or types of immunity are termed innate and acquired. Innate immunity, also known as genetic or species immunity, represents a wide range of immune protective factors that a person is born with. In contrast, acquired immunity becomes part of the host defenses by means other than heredity. Within this category, immune protection can be acquired naturally or artificially.

Natural acquired immunity is developed through the recovery from a specific infectious disease while artificial acquired immunity occurs when the host receives a vaccine or antitoxin. This category can be further subdivided by using the terms active (the host actively produces antibodies in response to a solution of antigens such as those in a vaccine) and passive (the host passively accepts preformed antibodies present in products such as an antitoxin).

When our immune system malfunctions, the consequences can range from microbial infections to cancer. Many nutritional supplement ingredients are effective in supporting immune system health. Some of the more popular and scientifically substantiated ingredients include:

1. Echinacea has been shown to stimulate the immune system by increasing the activity of certain immune cells and by promoting the release of cytokines (cellular communication and regulatory molecules) from these immune cells (1).

2. Elderberry contains flavonoid derivatives called anthocyanidins that appear to have immunomodulatory effects. These compounds in elderberry extract have been found to bind to viruses and block their ability to invade host cells (2). In this way, elderberry is thought to reduce the severity of viral flu symptoms.

3. Vitamin D3 has been known for quite some time as being important in supporting bone health. However, recently Vitamin D3 has also been shown to be a key component in enhancing the immune system. Sophisticated experiments have demonstrated that Vitamin D3 is essential for the activation of immune cells needed to seek out and destroy infectious invading microbes (3). Without this activation, infections such as influenza and the common cold appear to be more severe and longer lasting.

4. Scientific studies on ingredients such as zinc, Korean ginseng, Vitamin C, beta-glucans and arabinogalactans show that all of these enhance and improve the effectiveness of the immune system by increasing the protective activity of certain immune cells. Macrophages, neutrophils, NK (natural killer) cells and T-cells (T-lymphocytes) are responsible for attacking and neutralizing foreign, disease-causing microbes. Without the proper function of these immune cells, infectious diseases such as colds and the flu usually occur more frequently, are more severe, and have a longer duration.

As a pharmacy student and during my graduate school days, I was always interested in the concepts of immunology. However, back in those days, the association of immune function and the gut was either not mentioned or was discussed very superficially. Now that we understand how important a properly functioning gut is to the immune system, I'm fascinated by reading the many excellent scientific papers on this topic. A particularly intriguing aspect focuses on how gut bacteria may influence various disease processes while being involved with their beneficial role in digestion and metabolism.

In a previous Hot Topic paper, I described how the "Western diet" - high in fats and simple sugars - can reshape the gut microbial community (microbiome) and predispose humans to obesity and all of the health problems that accompany the obese state. Dietary fibers escape host digestion, but resident microbes in the distal gut (large intestine) metabolize these indigestible leftovers to yield short-chain fatty acids such as acetic, propionic and butyric acids. Not only do these acids contribute about 10% to our daily energy supply but they also impact the immune system.

Gut microbe-generated acetate interacts with immune cells to quiet an overactive immune system while propionic acid appears to promote the acquired immune response by acting on T-lymphocytes (4). Butyric acid is known to serve as an important energy source for gut endothelial cells thereby enhancing innate immunity.

We're all familiar with the benefits of the polyphenolic antioxidants. Recently, it has been found that the well-known ellagic acid, present primarily in berries and nuts, is metabolized by gut microbes to a class of compounds known as the urolithins. Specific urolithins are thought to reduce inflammation and thus protect against cancer (5).

We have focused on a few important aspects of gut health as they relate to a properly functioning immune system. However, keep in mind that our gut microbes have long been known to be part of other processes such as food digestion and the production of essential micronutrients.

On the downside, our gut bacteria can be directly linked to medical conditions such as obesity, inflammatory bowel disease, diabetes and cancer. Therefore, I believe that it's imperative that we continue toward a better understanding of this huge population of microbes that live in our gastrointestinal tract and other parts of our body. Another way of looking at this situation is that we are outnumbered. Believe it or not, the vast majority of cells that make up the human body are microbial cells.

1. Echinacea. Pharmacist's Letter/Prescriber's Letter Natural Medicines Comprehensive Database. 8th ed. Stockton, CA: Therapeutic Research Faculty ; 2010. p. 605.
2. Elderberry. Pharmacist's Letter/Prescriber's Letter Natural Medicines Comprehensive Database. 8th ed. Stockton, CA: Therapeutic Research Faculty ; 2010. p. 615.
3. Von Essen MR, et al. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nature Immunology. 2010; 11(4):344-349.
4. Fukuda S, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature. 2011 Jan 27;469(7331):543-547.
5. González-Sarrías A, et al. NF-kappaB-dependent anti-inflammatory activity of urolithins, gut microbiota ellagic acid-derived metabolites, in human colonic fibroblasts. British Journal of Nutrition. 2010 Aug;104(4):503-12.