gut microbiome

What does a leaky gut, and our gut microbiome, have to do with our immune system? Scientists are discovering that it has a lot to do with how well our immune system works.

Our intestines have a very thin lining that prevents substances other than nutrients to pass into our blood stream. Intestinal permeability is when the tight junctions (TJs) in the intestinal lining that control what passes through don't work properly and substances leak into the bloodstream. Imagine the tight junctions as doors and something is making the doors open to allow substances that normally don't pass through to pass through.

The gastrointestinal tract "together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens," according to Dr. Alessio Fasano's paper on "Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer."

Dr. Fasano, of Massachusetts General Hospital, discovered the protein Zonulin, "the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance." He is the foremost expert on gluten and Celiac Disease.

What does Celiac Disease and gluten have to do with a leaky gut? Gluten is the culprit. Why? Gluten, genetically modified (GM) in wheat has an unusual composition that cannot be completely digested. Gluten has too many proline and glutamine amino acids and our enzymes do not recognize this sequence. The same is true for GM barley and rye, said Dr. Fasano during his talk at the Gluten Summit. Gluten is comprised of two main proteins, gliadins and glutenins, and both are toxic for Celiac Disease patients. Gliadins triggers the release of Zonulin, which opens up the TJ, or doors, and allows gliadins and sometimes other molecules, to pass through. When gliadins are seen, it triggers an immune response, which leads to inflammation.

Zonulin is released in response to gluten which then loosens the tight junctions (TJs) of the intestinal wall. When gluten passes through the intestinal wall into the blood stream, it triggers the immune system resulting in inflammation.

Source: Scientific America, Inc..

When food molecules pass through, one can form food sensitivities in response to these molecules. When immune cells pass through, they can travel anywhere in the body, said Dr. Fasano. If the immune cells reach the joints, they can cause joint pain. If they reach the nerves, they can cause peripheral neuropathy. If they reach the skin, they can cause dermatitis herpetiformis and so forth. One theory is that the TJ-- or doors-- may remain open longer than usual possibly due to an overproduction of Zonulin. Scientists don't know why this happens, but in Celiac patients there is an up-regulation of Zonulin in the acute phase following exposure to gluten or microorganisms.

For many people, our immune system takes care of the gliadins and everything is fine. For others, depending on their genetic make-up or predisposition, the immune system goes awry. In Celiac patients, there is a miscommunication between the innate and the adaptive immune system and the adaptive immune system starts attacking its own cells, leading to gut damage. Celiac Disease is a genetic disorder and at least one of two genes is needed to develop Celiac; HLA-DQ2 and HLA-DQ8. Dr. Fasano believes these genes act like "docking stations" for gluten when it has been changed by transgutaminase and the immune system recognizes gluten as the enemy. In classic Celiac Disease the damage occurs in the intestine.

In gluten sensitivity, it only involves the innate immune system which leads to inflammation and symptoms, but will never lead to enteropapthy, stated Fasano. Symptoms of non-Celiac gluten sensitivity include the following: abdominal pain, headaches, foggy mind, chronic fatigue and depression. These symptoms long-term can lead to poor quality of life and possibly shorter life expectancy.

Dr. Fasano believes the gut is the most sophisticated immunological component in our body that is controlled by a neuroendocrine network. Our intestine is our interface with the environment. Information is exchanged in a highly controlled and coordinated manner. Our state of health or disease is the coordination of our genes and the environment and our "gut is the point of entry in which these two elements, they will meet." An epidemic of autoimmune diseases have developed over the last 40-50 years because we are unable to adapt to our fast changing environment.

"Once gluten is removed from the diet, serum Zonulin levels decrease, the intestine resumes its baseline barrier function, the autoantibody titers are normalized, the autoimmune process shuts off and, consequently, the intestinal damage (that represents the biological outcome of the autoimmune process) heals completely," says Dr. Fasano.

Currently Alba Therapeutics is conducting clinical trials on Larazotide acetate, a permeability inhibitors for Celiac Disease according to the company's website.

The composition of our gut bacteria is the key factor impacting intestinal physiology, where our microbiome helps the intestinal immune function to maturity, states Fasano. He said that 99% of the bacteria in the gut can't be cultured and that our microbiome is 100 times more complex genetically. Our microbiome affects how our genes are expressed.

As humans, we have a rudimentary genetic make-up of 25,000 genes, compared to an earthworm, that has 90,000 genes. Our microbiome is highly affected by our nutrition and environment and is impacted by pollution, chemicals and radiation. We are constantly exposed to antibiotics, not only from antibiotic usage, but also from the vegetable and animal products that we eat which are treated with antibiotics.

There are currently seven start-ups and there may be more that are focusing on gut microbiome for various type of diseases:

1) Seres Health

2) Second Genome

3) Vedanta Biosciences

4) Microbiome Therapeutics

5) ViThera Pharmaceuticals

6) Enterome Bioscience SA

7) Synlogic

In the meantime, a gluten-free diet seems to be the answer. For more information or comments, please email me at regina@biomarketinginsight.com.

gut microbiome

How a Leaky Gut and Gut Microbiome Can Affect Our Immune System

FIND CONTENT BY TYPE

Pharma IQ COMMUNITY

ADVERTISE WITH US

JOIN THE Pharma IQ COMMUNITY