Diabetes can start in your gut
Zonulin is a protein that plays a crucial role in regulating the permeability of tight junctions between cells in the intestinal lining. These tight junctions act as gatekeepers, controlling what substances can pass from the gut into the bloodstream. As these junctions weaken, as a result of food allergies and sensitivities and conditions like IBD, Celiac Disease, or other conditions, the chance of fragments of gut bacteria or toxins entering the bloodstream increases.
Zonulin was discovered by Dr. Alessio Fasano and his research team. They identified zonulin as a human analog to the Vibrio cholerae enterotoxin, which similarly affects intestinal permeability. This team’s discovery has been expanded upon by a number of researchers who have demonstrated not only Dr. Fasano’s work on intestinal permeability but also his suppositions and further research on the extent to which zonulin plays a role in systemic inflammation throughout the body that originates in the gut. This systemic inflammation is not only potentially at the root of many inflammatory diseases, but has been posited by Dr. Fasano as being the originator of most, or perhaps all autoimmune conditions.
The primary function of zonulin is to modulate the tight junctions in the intestinal epithelium. When zonulin levels increase, the tight junctions loosen, allowing larger molecules to pass through the intestinal barrier. This process is essential for nutrient absorption and immune surveillance. However, excessive zonulin can lead to increased intestinal permeability, commonly referred to as “leaky gut”. This condition allows not only nutrients but also potentially harmful substances like toxins, microbes, and undigested food particles to enter the bloodstream.
Increased intestinal permeability can trigger an immune response, leading to inflammation in the gut. This local inflammation can have systemic effects, as the immune system may start to attack these foreign particles, mistaking them for harmful invaders. This immune activation can lead to chronic inflammation, which is not confined to the gut but can spread to other parts of the body. For instance, inflammation in the gut has been linked to various autoimmune diseases, such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. Systemic inflammation can exacerbate these conditions, creating a cycle of ongoing immune response and tissue damage.
Understanding the role of zonulin in intestinal permeability has significant implications for treating and managing various inflammatory and autoimmune diseases. By targeting zonulin pathways, it may be possible to develop therapies that restore the integrity of the intestinal barrier, thereby reducing systemic inflammation and its associated health risks.
As always, the first step in targeting any pathways for intervention is through testing. Only through surveillance can practitioners diagnose the entire picture in any given patient and begin to craft treatment strategies that effectively get to the root of the problem. In this instance, we are describing two different testing regimes to assess both possible triggers to intestinal permeability and an assessment of the degree of damage to the intestinal lining. In the first case, one of the often hidden ways in which the intestinal tight junctions are damaged is through food allergies and sensitivities, or through gluten intolerance. Although both are partially assessed through observation, patient history, and elimination diets, targeting those elimination diets through food allergy and sensitivity testing can result in much more favorable outcomes. This is because food sensitivities can have a delayed onset of up to 72 hours for symptoms and foods can be hidden in dishes, and even patients with the strictest adherence to the rules can often miss specific foods that affect them. In addition, the dietary antigen test from Precision Point Diagnostic, the P88 DAT, also measures complement through C3d for each food tested, which means we identify the foods that may trigger a complement cascade in each patient, magnifying inflammatory response, and potentially causing greater damage to the tight junctions of the intestinal wall.
If food allergies and sensitivities are found in a patient, then the next step should be to test zonulin, to assess the extent of the damage. If there are no significant food allergies or sensitivities, but gut issues are present, the zonulin should still be assessed. Precision Point Diagnostics offers the Advanced Intestinal Barrier Assessment Test, as a stand-alone test, or as a discounted bundle with the P88 DAT (check your price sheet or contact customer service). This is because we firmly believe in the validity of the data for zonulin and other gut markers as an assessment of the degree of gut damage incurred from food allergies and sensitivities. It’s the logical next step to test a patient for those markers if they test positive for moderate to severe allergies or sensitivities on the P88, which may have been manifesting for years. The AIBA not only includes zonulin, but other useful gut markers including histamine and diamine oxidase (DAO), which give information about histamine balance and gut mucosal health and lipopolysaccharides (LPS) which are endotoxins produced by gram-negative bacteria that also give information about inflammation and intestinal permeability.
So, why use zonulin as a predictor for diabetes? In the context of diabetes, elevated levels of zonulin have been observed in both type 1 and type 2 diabetes patients. Research indicates that increased zonulin levels correlate with poor glycemic control and the presence of diabetes-related complications. This makes zonulin a valuable predictor for the onset and progression of diabetes. The ability of zonulin to indicate changes in intestinal permeability provides a unique insight into the early stages of diabetes development, potentially allowing for earlier intervention and better management of the disease.
Moreover, the relationship between zonulin and diabetes is supported by its role in modulating the immune system. Zonulin’s regulation of intestinal permeability affects the balance between tolerance and immunity to non-self antigens. When this balance is disrupted, it can lead to autoimmune responses that are characteristic of type 1 diabetes. Additionally, the chronic inflammation resulting from increased intestinal permeability is a known risk factor for insulin resistance, a hallmark of type 2 diabetes. Thus, monitoring zonulin levels can provide critical information about the inflammatory and immune processes underlying diabetes.
The predictive value of zonulin is further enhanced by its association with other metabolic parameters. Studies have shown that zonulin levels are directly linked to insulin resistance and lipid profiles, including total cholesterol, HDL, LDL, and triglycerides. This comprehensive metabolic insight makes zonulin a biomarker that can inform both the diagnosis and management of diabetes. By integrating zonulin measurements into clinical practice, healthcare providers can gain a more holistic understanding of a patient’s metabolic health and tailor interventions more effectively.
Zonulin’s role in regulating intestinal permeability and its association with systemic inflammation and immune responses make it a preferred predictor of diabetes. Its ability to provide early warning signs of disease onset and progression, coupled with its links to key metabolic parameters, underscores its potential as a valuable tool in diabetes management. As research continues to elucidate the mechanisms underlying zonulin’s effects, its application in clinical settings is likely to expand, offering new avenues for early diagnosis and personalized treatment strategies
Precision Point Diagnostics is proud to have been one of the first medical diagnostic laboratories to have offered zonulin as a clinically relevant marker in the United States.