The Interaction between the Gut and the Immune System

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The Interaction between the Gut and the Immune System


For centuries, humans have known about the delicate interaction between food consumed and the bodily reactions of the immune system. Dating back to antiquity, Hippocrates documented reactions after food intake similar to a food allergy or sensitivity.

Another example is the vitamin C deficiency known as scurvy, which has been recognized since the late 15th century. It took until the 1930’s when Albert Szent-Györgyi discovered vitamin C, and then worked with J.L. Svirbely in Hungary to make the connection between scurvy symptoms and lack of this vitamin.  Think about it, people said for over four centuries, “For some reason, if you eat citrus fruits, your gums won’t bleed.”

Even though scientists found these important and landmark discoveries about nutrition and health, we have mostly thought about the gut and the immune system as two separate entities or the two having very little to do with each other except in more extreme instances. Nowadays, researchers are looking closely into the highly complex interaction between the gut and the immune system, or the gut’s impact on the immune system. They are factoring in not only food, but also the environment and genetics. Their findings are leading to cures or preventative measures against cancer, immunodeficiencies, and the opposite immune response of autoimmune diseases.

This line of research is something researchers have appeared to dance around. They have pinpointed some diseases and the causes, mostly by other testing such as for presence of antibodies or simply trial and error.

Celiac Disease is a good example. When people with Celiac Disease eat glutens, their bodies have an immune reaction, which damages the gastrointestinal (GI) lining, causing malabsorption. Celiac Disease was figured out after many years of observation as well as trial and error. While the conclusion baffled medical professionals for years, the cause was simple: a person with celiac disease eats whole wheat bread (or other glutens) and subsequently has bloating, diarrhea, gas formation or some other reaction like blurred memory and poor cognition.

Researchers are still actively studying GI diseases, by applying how disruptions to the gut from a combination or food, environment, aging and genetics can lead to whole or other body diseases like multiple sclerosis, autoimmune thyroiditis, and rheumatoid arthritis.

The Ultimate Goal of the Gut and Immune System

The ultimate goal of the gut and immune system is to be balanced on an even keeled. Researchers call this gut homeostasis: letting beneficial nutrients in and keeping harmful foods, microbes and toxins out. Any major disruptions to any part of the system upset the delicate balance here, if the body cannot mount a proper response.

The Basics of the Intestinal Tract System

As you read more about the intestinal tract and new disease findings, it is good to have a basic idea of the various parts and their functions.

Microbiota – Consist of the 10-100 trillion symbiotic microbial cells such as bacteria, viruses, fungi, parasites and eukaryotes (cells containing DNA and a nucleus) that live in the gut. Beneficial microbiota are called “commensal” and vie for their place and space in the body, thus stopping pathogenic microbes from prevailing. The microbiota regulate the body’s innate (native) and adaptive (acquired) immune systems.

Host – Refers to the body where the microbiota live.

Microbiome – Consists of the genes the microbiota harbor. The microbiome is the name given to all of the genes inside these microbial cells.

Innate Immune System – Already present in the body, provides a first line of defense against many common microorganisms, and is essential for the control of common infections. However, it cannot always eliminate infectious organisms, and there are some pathogens that aren’t recognized.

Adaptive Immune System – Evolved to provide a more versatile means of defense, which provides increased protection against subsequent reinfection with the same pathogen. The cells of the innate immune system, however, play a crucial part in the initiation and subsequent direction of adaptive immune responses, as well as participating in the removal of pathogens that have been targeted by an adaptive immune response.

Mucosal Immune System – A specific immune system which basically protects the whole inner surface of the body such as the mouth, pharynx, saliva, tears, sweat and the respiratory, GI and urogenital tracts. Regardless of location in the body, the mucosal immune system shares similar anatomical organization and features. It is composed of three layers: the epithelial layer, lamina propria (LP) and the mucosal-associated lymphoid tissue (MALT). In the GI tract, MALT is referred to as gut-associated lymphoid tissue (GALT). The mucosal immune system is sometimes referred to as the mucosa.

Mucus Layer – Covers epithelial surfaces and lubricates the intestinal tract. Mucus can be regarded as the first line of intestinal physical defense against pathogens. It is sticky, just like the mucus you may cough up if you have a cold.

Intestinal Epithelium – A single cell layer of the mucosal immune system that forms the interface between the intestinal tract and internal environment of the body.

Microvilli – Microvilli are tiny, peak-like projections that are attached to the epithelium and face the inside of the small intestines. They increase the area of the free surface of the epithelium available for absorption.

Intestinal Epithelial Cells (IEC) – Consist of two types of mucosal barriers: physical barriers and chemical barriers. These barriers spatially segregate gut microbiota in the intestines and immune cells in the lamina propria to help prevent these systems from working at crossed purposes, which could result in intestinal inflammation.

Difficulties Encountered

Each individual’s gut microbiota is unique. For instance, identical twins share less than 50% of the same species-level bacterial groups. In fact, the researchers used type of birth – vaginal or caesarean – as a factor, too. Infants born vaginally harbor bacterial communities resembling those found in the vaginal microbiota of their mothers. Those delivered by caesarean section have bacterial characteristics of the skin and dominated by microbes such as Staphylococcus. Fetal delivery mode has also been hypothesized to influence immunological functions during the first year of life via the development of gut microbiota.

The specifics and even generalizations here are often debated. For instance, many studies determined that one population compared to another based on geographic region had more of one type of bacteria in their guts than another and vice versa. Then, a survey of all of these studies refuted this claim by analyzing the data differently.


Instead of evaluating several diseases, we thought we would look at one bacterial member of the microbiota, Prevotella, and their implications for health. The preliminary and complex results are fascinating.

A little background on Prevotella. They are genera of the Bacteroidetes phylum, which also includes the clinically important genera Bacteroides and PorphyromonasPrevotella strains are classically considered commensal bacteria due to their extensive presence in the healthy body and their rare involvement in infections.

New research is not only demonstrating the benefits of Prevotella, but also the problems the organism may create if amounts are imbalanced. Remember, the gut equilibrium is a balancing act that is affected not only by food, but also age, environment and genes. Additionally, these are more generalizations at this point in time than definitive conclusions. We have a lot more research to do!

Rheumatoid Arthritis –  Prevotella copri is strongly correlated with rheumatoid arthritis in people who are untreated and the disease is newly onset. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in these patients. The researchers also identified unique Prevotella genes that correlated with disease. [Note that human parvovirus strain B22 is also associated with rheumatoid arthritis.]

Dietary Fiber-Induced Improvement – Studies compared the gut microbiota composition of healthy subjects who showed improved glucose metabolism following 3-day consumption of barley kernel-based bread with those who responded least to this dietary intervention. The Prevotella-to-Bacteroides (P/B)ratio was higher in responders than non-responders after having this bread (a gluten).

Analysis showed that the gut microbiota of responders were enriched in Prevotella copri and had increased potential to ferment complex polysaccharides after eating the bread. These findings also show that Prevotella protects against Bacteroides-induced glucose intolerance.

Weight Loss – Individuals with a high Prevotella-to-Bacteroides ratio lost more body weight and body fat compared to individuals with low P/B. This confirms that individuals with a high P/B are more susceptible to weight loss on a diet rich in fiber.

Hypertension – Compared to the healthy controls, researchers found dramatically decreased microbial richness and diversity, and the Prevotella dominated gut enterotype. Interestingly, after fecal transplantation from hypertensive human donors to germ-free mice, the mice had elevated blood pressure. This demonstrates the direct influence of gut microbiota on blood pressure.

HIV – Studies have demonstrated that human immune deficiency virus (HIV) infection is associated with intestinal dysbiosis characterized by increased Prevotella and reduction in Bacteroides. Recent studies suggest that increased Prevotella in HIV is a driver for persistent inflammation in the gut leading to mucosal dysfunction and systemic inflammation.

W. Jean Dodds, DVM
Hemopet / NutriScan
11561 Salinaz Avenue
Garden Grove, CA 92843


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