Stool Test Deep Dive: Zonulin, Calprotectin & Microbiome Explained Gut barrier function and intestinal inflammation are measurable features of digestive health. Stool testing provides noninvasive markers that help clinicians and researchers distinguish between altered permeability and active inflammation. This article summarizes the clinical meaning of zonulin and calprotectin in stool, how the tests are used, and how they fit into broader microbiome assessment. What stool markers reveal Stool markers are biochemical or cellular signs recovered from fecal material. They reflect processes occurring in the intestinal lumen and mucosa, including microbial composition, immune activity, and mucosal integrity. Measuring specific markers can help differentiate inflammatory conditions, detect infections, or screen for increased gut permeability when symptoms are nonspecific. Zonulin: a marker of gut barrier regulation Zonulin is a physiologic regulator of tight junctions between enterocytes. Higher zonulin expression is associated with increased paracellular permeability in the small intestine. Clinically, elevated zonulin concentrations in stool (or blood/serum in some studies) have been correlated with conditions where barrier dysfunction is suspected, such as certain autoimmune disorders, food sensitivities, and post-infectious states. Interpretation requires clinical context: zonulin is one indicator among others rather than a definitive diagnostic test for “leaky gut.” Calprotectin: indicator of intestinal inflammation Calprotectin is a calcium- and zinc-binding protein abundant in neutrophils. When neutrophils migrate into the gut lumen during inflammation, calprotectin is released and can be quantified in stool. Elevated fecal calprotectin is a sensitive marker for neutrophil-driven intestinal inflammation and is commonly used to distinguish inflammatory bowel disease (IBD) from functional disorders such as irritable bowel syndrome (IBS). Serial calprotectin measurements can monitor response to therapy or disease activity. How these tests are used together Zonulin and calprotectin provide complementary information: zonulin relates to barrier permeability while calprotectin indicates active inflammation. A pattern of elevated zonulin with normal calprotectin may suggest increased permeability without prominent neutrophilic inflammation, whereas high calprotectin typically signals active mucosal inflammation that may warrant further diagnostic evaluation (e.g., endoscopy, imaging). Other stool tests and context Additional stool markers—such as lactoferrin, fecal occult blood testing, and pathogen PCR—help build a fuller picture. Microbiome profiling can identify dysbiosis patterns that correlate with symptoms or lab markers. For practical clinical pathways, these tests are combined with history, physical exam, laboratory studies, and imaging when appropriate. Resources and further reading For a focused overview of zonulin and calprotectin testing and how results are interpreted in a stool testing program, see the InnerBuddies discussion: [Zonulin Stool Test & Calprotectin Explained | InnerBuddies Gut Health](https://www.innerbuddies.com/blogs/gut-health/zonulin-stool-test-calprotectin-explained-innerbuddies-gut-health). For information on tracking recovery after fecal microbiota interventions, consult how InnerBuddies helps you track gut recovery after FMT, and for baseline microbiome concepts see understanding your microbiome: the key to optimal health and immunity. Additional product-oriented resources may be available, for example microbiome test. Summary Zonulin and calprotectin are useful stool markers that address different aspects of gut physiology: permeability and inflammation. Interpreting them alongside other stool markers and clinical findings supports evidence-based decision making in gastroenterology and gut-focused care.