What Infections Cause High Calprotectin?

Calprotectin is a protein primarily found within neutrophils, a type of white blood cell. When the body detects inflammation in the gastrointestinal tract, these neutrophils migrate to the site of irritation in the intestinal lining. During this immune response, the cells release calprotectin into the gut lumen. Measuring this protein in a stool sample, known as fecal calprotectin testing, provides a non-invasive way to detect active inflammation in the digestive tract.

Understanding Elevated Fecal Calprotectin

The measurement of fecal calprotectin is a widely used medical test to help distinguish between different causes of digestive symptoms. The test is particularly helpful in separating functional bowel disorders, which typically do not involve inflammation, from organic diseases that do. Irritable Bowel Syndrome (IBS), for instance, is a condition characterized by symptoms like abdominal pain and diarrhea but generally presents with normal or very low calprotectin levels.

A normal calprotectin level is typically below 50 micrograms per gram (\(\mu\)g/g) of stool, which suggests that significant intestinal inflammation is unlikely. Levels between 50 \(\mu\)g/g and 200 \(\mu\)g/g are considered a grey zone that warrants careful monitoring and potential retesting. When concentrations exceed 250 \(\mu\)g/g, it strongly suggests active inflammation, prompting further investigation. Extremely high values, sometimes over 600 \(\mu\)g/g, often correlate with severe inflammation seen in conditions like Inflammatory Bowel Disease (IBD) or acute infectious colitis.

Specific Infectious Agents That Raise Calprotectin

Infectious agents that invade or irritate the intestinal lining trigger a robust inflammatory response, leading to a significant spike in fecal calprotectin levels. This rise occurs because the body’s immune system dispatches large numbers of neutrophils to combat the invading pathogen, releasing their calprotectin stores. The highest elevations are typically associated with acute bacterial infections that cause invasive or toxin-mediated damage to the intestinal wall.

Bacterial pathogens such as Salmonella, Campylobacter, and Shiga toxin-producing Escherichia coli (E. coli) provoke intense neutrophil activity. Studies have shown that during the acute phase of infection, calprotectin levels can reach median values around 765 \(\mu\)g/g for Salmonella and 689 \(\mu\)g/g for Campylobacter. Clostridioides difficile infection is also a significant cause, producing toxins that damage the colon lining and resulting in colitis.

The severity of inflammation often correlates directly with the measured calprotectin concentration, making it a useful indicator of disease activity. Infections caused by certain tissue-invading parasites, such as Entamoeba histolytica, can also cause a substantial inflammatory response. These pathogens directly irritate the mucosa, causing ulceration and the recruitment of inflammatory cells.

Viral gastroenteritis, while causing acute symptoms, typically results in a less dramatic elevation compared to bacterial infections. Common viruses like Rotavirus and Norovirus generally lead to median calprotectin levels between 89 to 95 \(\mu\)g/g. This is above the normal threshold but significantly lower than values seen with invasive bacteria.

The Transient Nature of Infection-Related Elevation

A defining characteristic of infection-induced calprotectin elevation is its transient nature, distinguishing it from chronic inflammatory conditions. Once the body clears the pathogen, the inflammatory process subsides, and the intestinal lining begins to heal. This resolution is directly mirrored by a decrease in fecal calprotectin concentration.

Levels generally peak during the active phase of acute infection and then decline as the patient recovers. This normalization can take several weeks or a few months, depending on the initial severity and extent of damage to the gut lining. For example, severe infectious colitis may require more time for neutrophil migration to cease.

This pattern contrasts with conditions like IBD, where calprotectin elevation is sustained and requires ongoing therapy. Retesting after an infection resolves confirms the marker has returned to the normal range. If levels remain persistently high, it suggests the inflammation has not resolved and may indicate an underlying chronic condition or complication requiring further investigation.