SIBO and Stool Inflammatory Markers
SIBO does not cause elevated MMP-9, lactoferrin, beta-defensin 2, or eosinophil protein X on stool testing—these markers indicate mucosal inflammation from other conditions like inflammatory bowel disease, and their presence should prompt investigation for concurrent inflammatory pathology rather than attributing them to bacterial overgrowth alone. 1
Key Diagnostic Principle
When encountering elevated inflammatory markers in a patient with suspected SIBO, investigate alternative causes of inflammation rather than attributing it to bacterial overgrowth, as these markers are not elevated in SIBO patients. 1 The American Gastroenterological Association explicitly recommends treating SIBO and elevated inflammatory markers as separate conditions requiring distinct therapeutic approaches. 1
Understanding SIBO's Histologic Profile
SIBO presents with minimal to no inflammatory changes on tissue examination:
- More than half of duodenal biopsies from SIBO patients are histologically unremarkable, with villous blunting being the only feature more common in SIBO than controls (24% versus 7%). 2
- SIBO is characterized by bacterial overgrowth causing symptoms through excessive bacterial fermentation, not through inflammatory mechanisms. 3, 4
- The absence of elevated inflammatory markers does not exclude SIBO, as SIBO is diagnosed through breath testing or small bowel aspiration, not inflammatory biomarkers. 1
Specific Markers and Their Significance
Fecal Lactoferrin
- Elevated fecal lactoferrin indicates moderate to severe endoscopic inflammation, particularly in ulcerative colitis, with very low certainty of evidence for ruling in inflammation. 5
- Lactoferrin elevation reflects mucosal inflammatory disease, not bacterial overgrowth. 5
Fecal Calprotectin
- Elevated calprotectin (50-60 mg/g) has a pooled sensitivity of 0.81 and specificity of 0.87 for detecting organic inflammation in IBD patients. 1
- In post-surgical Crohn's patients, rising calprotectin indicates anastomotic recurrence rather than concurrent SIBO. 1
Low Secretory IgA (sIgA)
- Low sIgA suggests immune deficiency states such as common variable immunodeficiency (CVID), which itself is a risk factor for developing SIBO as a secondary condition. 5
- CVID presents with IgG <5 g/L plus low IgA or IgM, absence of plasma cells on biopsy, and recurrent infections. 5
Clinical Approach When Both Are Present
If a patient has confirmed SIBO plus elevated inflammatory markers, treat them as two separate conditions:
- For SIBO: Antibiotics such as rifaximin 550mg twice daily for 1-2 weeks. 1, 3
- For the inflammatory process: Anti-inflammatory therapy appropriate to the underlying condition (IBD, eosinophilic enteritis, autoimmune enteropathy, etc.). 1
Differential Diagnosis to Consider
When encountering this pattern of elevated inflammatory markers, investigate for:
- Inflammatory bowel disease (Crohn's disease or ulcerative colitis): Elevated inflammatory markers, bloody diarrhea, weight loss. 5
- Eosinophilic gastroenteritis: Massive eosinophilic infiltration, peripheral hypereosinophilia, multiple allergies. 5
- Autoimmune enteropathy: Intractable diarrhea, anti-enterocyte antibodies, lymphoplasmacytic infiltrate. 5
- Common variable immunodeficiency: Low total immunoglobulins, recurrent infections, poor vaccine response. 5
Common Pitfall to Avoid
Do not assume that all gastrointestinal symptoms and abnormal stool markers in a patient are explained by SIBO alone. SIBO often develops secondary to underlying diseases that themselves cause inflammation (Crohn's disease, motility disorders, immune deficiency). 5, 4 The presence of elevated inflammatory markers mandates investigation for these primary inflammatory conditions, as they require fundamentally different treatment approaches than SIBO and have significant implications for morbidity if left untreated. 1