Does SIBO Elevate Calprotectin?
No, SIBO does not elevate fecal calprotectin levels—multiple studies consistently demonstrate that calprotectin remains normal in SIBO patients, indicating the absence of neutrophilic intestinal inflammation. 1, 2, 3
Evidence Against Calprotectin Elevation in SIBO
The most authoritative guidance comes from the 2020 AGA Clinical Practice Update, which explicitly states there is insufficient evidence to support using inflammatory markers such as fecal calprotectin to detect SIBO. 4 This recommendation is based on consistent research findings:
Direct Research Evidence
Adult SIBO patients show no significant difference in fecal calprotectin concentrations compared to healthy controls (mean 43.0 ± 31.6 mg/kg vs 35.7 ± 20.7 mg/kg, p = 0.907), demonstrating that bacterial overgrowth does not trigger subclinical intestinal inflammation involving neutrophils. 1
Pediatric SIBO patients similarly demonstrate normal calprotectin levels (median 36.0 mg/kg) that do not differ from healthy children (median 29.5 mg/kg, p = 0.07), confirming the absence of neutrophil-mediated inflammation across age groups. 2
Cystic fibrosis patients with documented SIBO show no correlation between positive breath tests and calprotectin levels, indicating that bacterial overgrowth itself does not drive intestinal inflammation even in vulnerable populations. 3
Important Clinical Exception: Systemic Sclerosis
One notable exception exists in systemic sclerosis (SSc) patients, where a strong association between elevated calprotectin (≥275 μg/g) and SIBO has been documented, with sensitivity of 0.93 and specificity of 0.95 for predicting SIBO. 5 However, this relationship likely reflects:
- The underlying autoimmune inflammatory process of SSc affecting the gastrointestinal tract 5
- Severe dysmotility and structural changes unique to SSc that create both SIBO and inflammation 5
- Not a direct causal relationship where SIBO itself elevates calprotectin 5
Clinical Implications
When you encounter elevated calprotectin in a patient with suspected SIBO, you must investigate alternative causes of inflammation rather than attributing it to bacterial overgrowth:
- Consider inflammatory bowel disease (IBD), where calprotectin at 50-60 mg/g has pooled sensitivity of 0.81 and specificity of 0.87 for detecting organic inflammation 6
- Evaluate for microscopic colitis, celiac disease, or chronic infections 6
- In post-surgical Crohn's patients, rising calprotectin indicates anastomotic recurrence rather than concurrent SIBO 6
If both SIBO and elevated calprotectin are present, treat them as separate conditions requiring distinct therapeutic approaches—antibiotics for SIBO (typically rifaximin 550mg twice daily for 1-2 weeks) and anti-inflammatory therapy for the inflammatory process. 6, 4
Common Pitfall to Avoid
Do not delay investigation for inflammatory bowel disease or other serious pathology by attributing elevated calprotectin to SIBO—this misattribution can lead to significant diagnostic delays and worse outcomes, as calprotectin specifically reflects neutrophilic inflammation that SIBO does not cause. 1, 2, 4