Fecal Calprotectin (FC) is a non-invasive laboratory marker used in gastroenterology to assess inflammation within the gastrointestinal tract. This simple stool test is an important tool for initial evaluation when doctors suspect an inflammatory condition. Its primary purpose is to help distinguish between Inflammatory Bowel Diseases (IBD), such as Crohn’s disease and Ulcerative Colitis, and non-inflammatory conditions like Irritable Bowel Syndrome (IBS). By providing an objective measure of intestinal inflammation, FC helps guide the decision about whether a patient requires further invasive testing, such as a colonoscopy.
The Function of Calprotectin
Calprotectin is a protein released primarily by neutrophils, a type of white blood cell and a first responder to inflammation. These immune cells contain large amounts of calprotectin. When the lining of the gut becomes inflamed, such as in Crohn’s disease, neutrophils migrate to the site of injury as part of the immune response.
As these neutrophils fight inflammation and eventually die, they release their contents, including calprotectin, into the intestinal lumen. This protein is remarkably stable and resistant to degradation in the gut, meaning it can be easily measured in a stool sample. A high level of Fecal Calprotectin correlates directly with the presence and intensity of active inflammation in the intestinal wall.
This mechanism explains why the test is useful in differentiating Crohn’s disease from functional disorders like IBS. Conditions such as IBS are not characterized by the migration of large numbers of neutrophils to the gut lining, so they do not cause a significant elevation in FC levels. Calprotectin acts as a quantitative marker for the degree of mucosal inflammation, which is a hallmark of IBD.
Numerical Cutoffs for Active Disease
The interpretation of Fecal Calprotectin results relies on established numerical cutoffs, measured in micrograms per gram of stool (µg/g). A low FC level, typically less than 50 µg/g, suggests the patient’s symptoms are likely due to a non-inflammatory disorder, such as IBS. Levels in this low range also strongly suggest that a patient with established Crohn’s disease is in clinical remission. The diagnosis of IBD is highly unlikely with a result below this threshold.
An intermediate, or “gray zone,” is often defined as a result between 50 µg/g and 200 µg/g or 250 µg/g. Results in this range are difficult to interpret and require caution. They could indicate very mild inflammation, a transient intestinal infection, or inflammation caused by non-steroidal anti-inflammatory drugs (NSAIDs). Doctors often correlate these intermediate levels with the patient’s symptoms and other blood test results, sometimes requiring a repeat test to monitor the trend.
The threshold for a result strongly suggestive of active inflammatory disease, such as Crohn’s, is typically set higher than 200 µg/g or 250 µg/g. Levels above this mark are highly correlated with endoscopically visible inflammation. These results usually prompt the doctor to recommend an invasive investigation, like a colonoscopy, for confirmation. A cutoff of 250 µg/g, for example, has been associated with the presence of large ulcers in Crohn’s disease.
No single cutoff is universally perfect due to variations in laboratory testing methods and patient populations. Some studies suggest that a threshold of 150 µg/g is strongly indicative of endoscopically active disease. Conversely, for inflammation located only in the small bowel, the optimal cutoff for maximum accuracy can be higher, sometimes exceeding 265 µg/g. The higher the FC level, the more likely it is that significant mucosal inflammation is present.
Using Calprotectin to Monitor Crohn’s
Once Crohn’s disease is diagnosed, Fecal Calprotectin shifts from a diagnostic tool to a longitudinal monitoring instrument. The test is used repeatedly to assess disease activity and treatment efficacy, offering a less invasive alternative to repeated endoscopies. A goal of Crohn’s therapy is achieving mucosal healing, and a significant drop in FC levels reliably indicates this healing.
The FC level can effectively predict the likelihood of a future relapse in asymptomatic patients. Patients with elevated FC levels have a significantly higher probability of experiencing a clinical flare-up compared to those with consistently low levels. Regular monitoring can facilitate an early treatment adjustment before symptoms become severe.
Normalizing the FC level after diagnosis is associated with a significantly reduced risk of disease progression, including fewer hospitalizations and surgeries. The marker is considered superior to symptom-based scoring systems and some blood markers, like C-reactive protein, for accurately reflecting the degree of inflammation in the gut. This ability to track subclinical inflammation makes FC a foundational part of the modern “treat-to-target” approach in Crohn’s management.