Zonulin, a marker of intestinal permeability, can also give us insights into a patient’s oxidative stress stemming from gut dysbiosis.

Zonulin is a protein that plays a crucial role in regulating intestinal permeability by modulating the tight junctions between cells in the gut lining. When these tight junctions are disrupted, it can lead to increased intestinal permeability, commonly referred to as “leaky gut.” Gut dysbiosis can lead to an increase in the production of zonulin. Specifically, certain food components, such as gluten and gliadin, are known to trigger the release of zonulin, as can chronic food allergies and sensitivities to other foods. Additionally, dysbiosis caused by conditions like small intestinal bacterial overgrowth (SIBO), candida overgrowth, and parasitic infections can also elevate zonulin levels.

When zonulin levels rise, the tight junctions between the cells lining the gut become less effective, allowing larger molecules, toxins, and even bacteria to pass through the gut lining into the bloodstream. This process is known as increased intestinal permeability or “leaky gut”. The presence of these foreign substances in the bloodstream can trigger an immune response, leading to inflammation and potentially contributing to various autoimmune and inflammatory diseases. Research has shown that increased zonulin levels are associated with several conditions, including celiac disease, type 1 diabetes, and inflammatory bowel diseases. For instance, in celiac disease, the ingestion of gluten leads to a significant increase in zonulin levels, which in turn increases intestinal permeability and allows gluten peptides to enter the bloodstream, triggering an autoimmune response. Indeed, zonulin may be at the root of many autoimmune diseases, as opening the tight junctions allows many sorts of specific materials to enter the bloodstream, all of which may produce an independent immune response.

Zonulin is also closely linked to oxidative stress. Immune reactions to the substances that enter the bloodstream through intestinal permeability create an inflammatory response, generating reactive oxygen species (ROS), which are key contributors to oxidative stress. The influx of foreign substances due to increased intestinal permeability can activate immune cells, leading to the production of inflammatory cytokines, which further exacerbate oxidative stress. Research suggests a connection between elevated zonulin levels and various diseases associated with oxidative stress, including inflammatory bowel disease, type 1 diabetes, autoimmune disorders, and metabolic syndrome.

Oxidative stress occurs when there is an imbalance between free radicals and antioxidants in the body. Free radicals are unstable molecules that can damage cells, proteins, and DNA by stealing electrons through a process called oxidation. Antioxidants are molecules that can donate an electron to a free radical without becoming unstable themselves, thus neutralizing the free radical and preventing cellular damage. Free radicals are produced naturally in the body as a byproduct of normal metabolic processes, such as energy production in the mitochondria. However, external factors can increase the production of free radicals, such as triggers to an inflammatory response, toxins, radiation, etc.

When the balance between free radicals and antioxidants is disrupted, oxidative stress can occur, leading to cellular and tissue damage. This damage can affect various parts of the body, including:

• DNA: Oxidative stress can cause mutations and damage to DNA, which can lead to cancer.
• Proteins: It can alter the structure and function of proteins, affecting enzymes and other cellular functions.
• Lipids: Lipid peroxidation can damage cell membranes, leading to cell death.

Oxidative stress can become systemic when the damage spreads beyond the initial site of free radical production. This can happen through several mechanisms:

• Inflammation: Oxidative stress can trigger an inflammatory response, which can produce more free radicals, creating a vicious cycle.
• Circulatory System: Free radicals can enter the bloodstream, spreading oxidative stress throughout the body.
• Cell Signaling: Oxidative stress can disrupt normal cell signaling pathways, leading to widespread cellular dysfunction.

Without intervention, chronic oxidative stress can lead to a decline in quality of life due to its association with various diseases and conditions:

• Cardiovascular Diseases: Oxidative stress contributes to the development of atherosclerosis, hypertension, and heart disease.
• Neurodegenerative Diseases: Conditions like Alzheimer’s and Parkinson’s disease are linked to oxidative damage in the brain.
• Diabetes: Oxidative stress can impair insulin signaling and contribute to the development of type 2 diabetes.
• Aging: Accelerated aging and age-related diseases are often associated with oxidative stress.

Oxidative stress is a complex process that can have significant impacts on the body and overall health. Understanding its mechanisms and effects is crucial for developing strategies to mitigate its harmful consequences. Lifestyle changes, such as a diet rich in antioxidants, regular exercise, and avoiding exposure to environmental toxins, can help manage oxidative stress and improve quality of life. To start this process, it’s first necessary to assess a patient through diagnostic testing to understand the root of the problem, assess the degree of the damage, and pinpoint the best modalities for intervention to combat the problem.

The intricate relationship between gut dysbiosis, inflammation, and oxidative stress is why we created the Gut-Ox Stress test at Precision Point Diagnostics. As a functional diagnostics laboratory, Precision Point Diagnostics has always offered testing solutions that look for the root cause of conditions and that follow the progression of disease from initial triggers to systemic impact on the body. In the case of the Gut-Ox Stress test, we analyze levels of sIgA, zonulin IgM/IgA/IgG, LPS IgM/IgA/IgG, Total Glutathione, F-2 Isoprostane, and 8-OHdG to trace the path of gut dysbiosis to leaky gut, to inflammation, and oxidative stress. These markers help tell a much more complete story about both the state and impact of intestinal permeability, the effect that has on raising levels of oxidative stress, and the degree of impact on cellular membrane, mitochondrial, and DNA health. Having this sort of comprehensive surveillance of gut and oxidative health together can be a game changer for the diagnosis and treatment of some of the most difficult to analyze root causes in a patient. An added bonus with the Gut-Ox Stress test is that it can be self-collected by the patient at home- no phlebotomist required, and dropshipping to your patient is available as long as the practitioner orders the test.

In cases where suspected food allergies or sensitivities are suspected to be the triggers for gut dysbiosis, this test is available bundled with our best-selling P88-DIY Dietary Antigen Test, which adds in initial triggers in the form of food allergens and sensitivities that can set a patient down the path of gut dysbiosis, inflammation, and systemic oxidative damage. Additional analytes added when ordering the P88/Gut-Ox Bundle include 88 foods and four independent immune reactions to each, including IgE, IgG, IgG4, and C3d. The P88 portion of the test is also DIY, meaning all analytes for the bundle can be collected at home.

Patients who suffer from gut dysbiosis present a riddle that must be unraveled to determine the specifics of their case. The Gut-Ox Stress test is a powerful tool to add to your arsenal for diagnosis and treatment.