Inflammation is the body’s natural immune response to injury, infection, or harmful stimuli. It is a protective process that aims to eliminate the cause of cell injury, clear out damaged cells, and begin tissue repair.  Acute inflammation is a short-term, healing response.   Chronic inflammation is a long-lasting, low-level activation of the immune system that persists for months or even years. It can silently damage tissues and organs over time. Calprotectin and zonulin are biomarkers commonly used to assess intestinal inflammation and intestinal permeability, respectively.

 

What is Calprotectin?

Calprotectin is a protein released by neutrophils, a type of white blood cell. When there is inflammation in the gastrointestinal tract, neutrophils move to the area and release calprotectin, resulting in an increased level in the stool.  Calprotectin is typically measured in the stool (fecal calprotectin). Elevated fecal calprotectin levels occur in inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis.  It is what differentiates between IBS (irritable bowel syndrome) from IBD.

What are the potential symptoms of high calprotectin?   The most common symptoms would be:

  • Abdominal pain or cramping
  • Diarrhea
  • Blood or mucus in the stool
  • Urgency to defecate
  • Fatigue
  • Weight loss
  • Nausea or vomiting

Inflammation - Leaky Gut

What is Zonulin?

Zonulin is a protein that regulates the permeability of tight junctions between cells of the digestive tract lining. Zonulin can be measured in the blood serum or stool.

High zonulin levels are indicative of increased intestinal permeability.  With increased permeability, larger molecules or antigens can pass into the bloodstream such as partially digested food particles, toxins, pathogenic bacteria or yeast and endotoxins (lipopolysaccharides or LPS).  When these substances cross into the bloodstream, the immune system triggers an inflammatory response.

These larger molecules are normally filtered out by the gut lining, but now they are triggering immune responses, which may contribute to systemic inflammation sometimes referred to as “leaky gut.”

High zonulin levels may be manifested in the following conditions.

  • Immune system-Chronic inflammation, autoimmune disease
  • GI tract- IBS, food sensitivities, bloating
  • Metabolism- Insulin resistance, metabolic syndrome
  • Brain- Anxiety, depression, fatigue, brain fog
  • Skin-Eczema, acne, psoriasis

It is helpful to test for both calprotectin and zonulin. Calprotectin can identify if there is active inflammation.  Zonulin identifies if the gut barrier is compromised.  Potential results could mean the following:

  • High calprotectin + high zonulin: Suggests inflammation with compromised gut barrier – seen in IBD, infections, or chronic systemic diseases.
  • Normal calprotectin + high zonulin: Suggests no current inflammation but increased gut permeability – may indicate GI dysfunction.
  • High calprotectin + normal zonulin: Active inflammation without significant permeability issues (possible in acute flare-ups of IBD).

How to improve calprotectin and zonulin levels?

First, it is important to determine the root cause of the problem.

When it comes to calprotectin, potential causes include IBD, GI infections, or other gastrointestinal disorders.

In contrast, zonulin levels may be influenced by different factors. These include gluten (found in wheat, barley, and rye), gut dysbiosis (an imbalance in gut bacteria), chronic stress, a poor diet high in processed foods and sugar, infections such as Candida, SIBO, or parasites, and the use of certain medications like NSAIDs and antibiotics.

At The Unconventional Dietitians, we offer GI Map testing to help identify both calprotectin and zonulin levels. Once the root cause is identified, you can work with one of our RDs to implement a comprehensive gut-healing protocol. This typically includes a real-food approach, along with targeted supplements such as Omega-3s, glutamine, and probiotics, among others, based on your specific needs. To get started, you can schedule an appointment by clicking here.

Ultimately, by using calprotectin and zonulin levels to pinpoint the source of inflammation, we can support you in your healing journey and guide you toward improved health and well-being.

Lisa is a registered dietitian with a degree in Administrative Dietetics from Brigham Young University. She has built a diverse career in clinical, long-term care, and community nutrition, including her work as a high-risk nutritionist for Women, Infants, and Children (WIC). Her lifelong mission is to help others heal and thrive through the power of food.