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September 08, 2025

Fecal Eosinophil Protein X: What This Gut Inflammation Marker Reveals

Fecal eosinophil protein X is a stool marker of eosinophil-driven gut inflammation. Discover how it’s used in the Gut Zoomer to guide personalized treatment.

Fecal Eosinophil Protein X: A Key Biomarker of Gut Inflammation

Introduction

When patients experience chronic digestive symptoms—such as abdominal pain, diarrhea, constipation, bloating, or unexplained food reactions—clinicians must determine whether the cause is functional (like irritable bowel syndrome) or inflammatory (such as food allergies, eosinophilic disorders, or inflammatory bowel disease).

Among the biomarkers that help uncover hidden gut inflammation is fecal eosinophil protein X (EPX). Although less commonly discussed than calprotectin or lactoferrin, fecal EPX provides unique insight into eosinophil-driven inflammation in the gastrointestinal tract.

Elevated EPX levels can indicate allergic responses, food sensitivities, eosinophilic gastrointestinal disorders, and immune-mediated gut inflammation. This makes it a valuable marker in both conventional gastroenterology and functional medicine.

In this article, we’ll explore everything you need to know about fecal EPX:

  • What it is and why it matters.

  • Conditions associated with elevated fecal EPX.

  • How the test is performed.

  • Why it is included in advanced stool testing.

  • How EPX results can be used to guide treatment and optimize health.

What is Eosinophil Protein X?

Eosinophil protein X (EPX)—also known as eosinophil-derived neurotoxin (EDN)—is a cationic granule protein released by eosinophils, a type of white blood cell involved in immune responses.

Eosinophils are best known for their role in:

  • Allergic reactions (as in asthma, hay fever, or food allergies).

  • Parasitic infections.

  • Chronic inflammation in the gut and other tissues.

When eosinophils are activated in the gastrointestinal tract, they release granule proteins like EPX into the intestinal lumen. These proteins are then excreted in stool, where they can be measured as markers of inflammation.

Why EPX is Important

Unlike calprotectin, which reflects neutrophil-driven inflammation, fecal EPX is more specific for eosinophilic activity. This distinction is important because eosinophil-mediated inflammation often points toward:

  • Food allergies or sensitivities.

  • Eosinophilic gastrointestinal disorders (EGIDs).

  • Atopic conditions with gut involvement.

Thus, fecal EPX gives clinicians a different “lens” through which to view gut health.

Conditions Associated with Elevated Fecal EPX

Elevated fecal eosinophil protein X levels can be seen in a variety of clinical contexts. Some of the most relevant include:

1. Eosinophilic Gastrointestinal Disorders (EGIDs)

  • Eosinophilic esophagitis, gastritis, and colitis are characterized by high eosinophil infiltration of the GI tract.

  • Patients may present with abdominal pain, reflux, dysphagia, or chronic diarrhea.

  • Fecal EPX is often elevated in these patients and can help support diagnosis and monitoring.

2. Food Allergies and Food Sensitivities

  • IgE-mediated food allergies and non-IgE food sensitivities can both drive eosinophil activation.

  • Elevated fecal EPX may help identify immune responses to dietary triggers, especially when paired with elimination diets or food sensitivity testing.

3. Parasitic Infections

  • Many intestinal parasites provoke a strong eosinophilic response.

  • In patients with travel history or unexplained eosinophilia, elevated fecal EPX may suggest further parasitology testing.

4. Atopic Conditions

  • Patients with asthma, eczema, or allergic rhinitis may also have eosinophilic inflammation in the gut, reflected by elevated EPX.

5. Inflammatory Bowel Disease (IBD)

  • Although calprotectin is the most common stool marker for IBD, studies show that fecal EPX can also be elevated in Crohn’s disease and ulcerative colitis, particularly in subsets of patients with high eosinophil activity.

6. Irritable Bowel Syndrome with Inflammation

  • While IBS is typically considered a “functional” disorder, some patients demonstrate subtle immune activation.

  • Elevated fecal EPX in IBS may point toward an inflammatory or food-triggered component.

How Fecal EPX is Tested

  • Sample type: Stool.

  • Method: Immunoassays (e.g., ELISA) detect EPX levels in fecal samples.

  • Standardization: Reference ranges vary, but higher levels consistently reflect increased eosinophilic inflammation.

EPX is not as widely available in conventional hospital labs as calprotectin. However, it is included in advanced functional stool testing panels, such as the Gut Zoomer, because of its unique ability to identify eosinophil-mediated inflammation.

Why Fecal EPX is Included in the Gut Zoomer

The Gut Zoomer test is designed to provide a comprehensive picture of gut health. While microbiome diversity and bacterial balance are important, so too is the immune response in the gut.

Fecal EPX is included in the Gut Zoomer because:

  1. It detects allergic or eosinophilic inflammation that calprotectin might miss.

  2. It helps personalize dietary interventions, identifying patients who may benefit most from elimination diets or food sensitivity testing.

  3. It supports identification of EGIDs, which are often underdiagnosed.

  4. It adds an immune perspective to microbiome data, bridging the gap between gut ecology and host response.

By combining fecal EPX with markers like calprotectin, secretory IgA, and zonulin, the Gut Zoomer provides a multi-dimensional view of gut health that can’t be obtained from conventional labs alone.

Interpreting Fecal EPX Results

Low or Normal Levels

  • Suggest little to no eosinophil-mediated inflammation.

  • In symptomatic patients, low EPX levels may point toward non-inflammatory causes (motility, microbiome imbalance, functional disorders).

Moderately Elevated Levels

  • Suggest mild allergic or food sensitivity reactions.

  • May also be seen in low-grade eosinophilic colitis or during mild parasitic infection.

High Levels

  • Strongly suggest eosinophilic GI disorders, food allergy, or significant gut immune activation.

  • Often associated with more severe digestive symptoms.

  • May require further testing, such as endoscopy or food allergy panels.

Using Fecal EPX in Clinical Practice

1. Identifying Food Triggers

  • Elevated EPX can help pinpoint patients with hidden food sensitivities or allergies.

  • These patients often benefit from elimination diets, low-allergen protocols, or targeted nutritional interventions.

2. Monitoring Eosinophilic GI Disorders

  • Patients with eosinophilic esophagitis, gastritis, or colitis can use fecal EPX to track disease activity and treatment response.

3. Supporting Gut Healing Protocols

  • Elevated EPX often improves with gut-healing protocols that reduce inflammation, balance the microbiome, and strengthen gut barrier integrity.

  • Peptides such as BPC-157 and KPV, along with nutrients like quercetin, curcumin, and omega-3 fatty acids, can help reduce eosinophilic inflammation.

4. Differentiating IBS from Inflammatory Causes

  • In patients with IBS-like symptoms, a high EPX level suggests immune involvement, guiding more targeted treatment.

Functional Medicine Perspective

From a functional and integrative medicine standpoint, fecal EPX is especially valuable because it reflects a type of gut inflammation that often goes undetected in conventional testing. Many patients with chronic GI symptoms have already had “normal” colonoscopies or basic labs.

By measuring EPX, we can:

  • Reveal immune activity linked to food reactions.

  • Uncover subtle eosinophilic inflammation that drives symptoms.

  • Integrate results with microbiome and barrier markers for a holistic view of gut health.

This leads to more personalized treatment plans, targeting not only symptoms but the root cause of inflammation.

Factors That Influence EPX Levels

When interpreting EPX results, it’s important to consider factors that can raise or lower values:

  • Medications: Corticosteroids or antihistamines may suppress eosinophilic activity.

  • Diet: Recent exposure to food allergens can temporarily raise EPX.

  • Infections: Parasitic infections are a classic cause of elevated EPX.

  • Comorbidities: Atopic conditions (asthma, eczema, allergies) increase the likelihood of elevated EPX.

Treatment Strategies for Elevated EPX

If fecal EPX is elevated, a root-cause approach is needed. Interventions may include:

  1. Dietary Therapy

    • Elimination of common allergens (gluten, dairy, soy, eggs, peanuts, shellfish).

    • Low-histamine or low-FODMAP diets for sensitive patients.

  2. Supplements and Nutrients

    • Quercetin: Stabilizes mast cells and reduces allergic inflammation.

    • Curcumin: Potent anti-inflammatory.

    • Omega-3 fatty acids: Support immune balance and lower eosinophil activity.

    • Immunoglobulins (IgG supplements): Help neutralize food antigens.

  3. Peptide Therapy

    • BPC-157: Supports gut lining repair.

    • KPV: Reduces gut inflammation, particularly eosinophilic activity.

  4. Microbiome Support

    • Probiotics (such as Lactobacillus rhamnosus GG and Bifidobacterium breve) may help modulate allergic inflammation.

  5. Lifestyle Medicine

    • Stress management, as stress can worsen immune reactivity.

    • Sleep optimization to regulate immune balance.

Example Case

A 35-year-old woman presents with bloating, diarrhea, eczema, and multiple food intolerances. Conventional GI workup is unrevealing.

The Gut Zoomer reveals:

  • Elevated fecal EPX.

  • Dysbiosis with low beneficial bacteria.

  • Elevated zonulin, suggesting increased intestinal permeability.

A personalized plan is implemented, including an elimination diet, probiotics, quercetin, and peptide therapy (BPC-157 + KPV). After three months, her symptoms improve dramatically, and repeat EPX levels normalize—providing objective evidence of gut healing.

Conclusion

Fecal eosinophil protein X (EPX) is a powerful stool biomarker that reveals eosinophil-driven inflammation in the gastrointestinal tract. It plays a critical role in diagnosing and managing food allergies, eosinophilic GI disorders, parasitic infections, and subtle immune-mediated gut inflammation.

Although not as widely known as calprotectin, fecal EPX provides unique insight into allergic and immune-mediated processes in the gut. That is why it is included in advanced stool testing panels like the Gut Zoomer, which combine microbiome analysis with inflammatory and immune markers for a complete picture of gut health.

By using fecal EPX to guide treatment, clinicians can personalize interventions, reduce inflammation, and help patients achieve true gut healing and systemic health optimization.

References

  1. Carlens J, et al. Fecal eosinophil protein X in children with gastrointestinal disease. Acta Paediatr. 2007.

  2. Røseth AG, et al. Assessment of inflammatory bowel disease activity by measurement of fecal neutrophil markers. Scand J Gastroenterol. 1999.

  3. Oka A, et al. Eosinophil-derived neurotoxin: A biomarker for eosinophilic esophagitis and other eosinophilic gastrointestinal disorders. Allergy Asthma Proc. 2018.

  4. Konikoff MR, et al. Eosinophil-derived proteins in the diagnosis and monitoring of eosinophilic gastrointestinal diseases. Clin Exp Allergy. 2006.

  5. Carlson M, et al. Fecal eosinophil granule proteins predict disease activity in ulcerative colitis. Am J Gastroenterol. 2002.