What is the best way to test for Small Intestine Bacterial Overgrowth (SIBO) in a patient with foul-smelling stools, flatulence, and diarrhea triggered by food intake?

How to Test for SIBO

In patients with high pretest probability of SIBO (those with anatomical abnormalities, prior small bowel surgery, pseudo-obstruction, or diverticulosis), proceed directly to an empirical trial of antibiotics rather than testing. 1 For all other patients with suspected SIBO, combined hydrogen-methane breath testing is the recommended first-line diagnostic approach. 2, 3

First-Line Testing: Breath Tests

Combined hydrogen and methane breath testing is more accurate than hydrogen-only testing and should be the initial diagnostic method. 4, 2, 3 This approach identifies both hydrogen-dominant and methane-dominant SIBO, which would be missed by hydrogen testing alone. 2, 3

Substrate Selection

• Glucose breath testing is preferred over lactulose due to higher specificity, though lactulose has slightly better sensitivity. 2, 3
• Glucose testing is more specific because it avoids the confounding issue of rapid orocecal transit that can produce false-positive early hydrogen peaks with lactulose. 1, 3
• Do not use lactose, fructose, or sorbitol as substrates for SIBO diagnosis—these test for carbohydrate malabsorption, not bacterial overgrowth. 3

Key Limitations of Breath Testing

Breath tests have significant methodological problems that clinicians must understand: 1

• Sensitivity ranges from only 17-68% depending on the substrate and methodology used. 1
• Specificity is better at 70-100% when transit time is properly measured. 1
• A positive test reinforces clinical suspicion, but a negative test does not exclude SIBO. 1
• Fast orocecal transit (common after intestinal resection) can cause false-positive results by producing early hydrogen peaks from colonic fermentation rather than small bowel overgrowth. 1

Second-Line Testing: Small Bowel Aspirate Culture

When breath testing is unavailable, inconclusive, or in patients requiring endoscopy for other reasons, obtain small bowel aspirate via upper endoscopy. 1, 2, 5

Proper Technique to Avoid Contamination

The technique is critical to prevent false-positive results from oropharyngeal contamination: 2, 5

• Do not aspirate during intubation. 2, 5
• Flush 100 mL of sterile saline into the duodenum. 2, 5
• Flush the endoscope channel with 10 mL of air. 2, 5
• Turn down suction and allow fluid to settle for several seconds. 2, 5
• Aspirate ≥10 mL into a sterile trap and send immediately to microbiology. 2, 5

Important Caveats

• Coordinate with your microbiology laboratory before performing the procedure to ensure they can properly process and report small bowel cultures. 5
• Culture is traditionally considered the "gold standard" but has significant limitations: poor standardization, potential contamination, sampling error, and inability to access all portions of the small bowel. 1, 6
• Positive results show growth of colonic bacteria in the small intestine sample. 5
• Culture of unwashed mucosal biopsies may be an alternative to jejunal aspirates. 1

Clinical Decision Algorithm

High Pretest Probability (Skip Testing)

Proceed directly to empirical antibiotic trial in patients with: 1

• Small bowel dilatation
• Small bowel diverticulosis
• Prior small bowel surgery or resection
• Intestinal pseudo-obstruction
• Chronic proton pump inhibitor use with typical symptoms 4

Low to Moderate Pretest Probability (Test First)

Perform breath testing to: 1, 4

• Confirm the diagnosis before antibiotics (antibiotic stewardship)
• Establish the cause of symptoms
• Differentiate SIBO from other conditions causing similar symptoms

Additional Diagnostic Considerations

Screen for Malabsorption

Check for fat-soluble vitamin deficiencies (A, D, E, K) in all patients with suspected SIBO because bacterial overgrowth causes bile salt deconjugation leading to malabsorption. 2, 5

Check Vitamin B12 and Folate

• Bacterial overgrowth causes B12 malabsorption through bacterial consumption and bile salt deconjugation. 4
• Folate levels may be elevated (bacteria produce folate). 6
• B12 deficiency is significantly associated with hydrogen-producing SIBO. 4

When to Consider Endoscopy Beyond Aspirate

Endoscopy with biopsies is indicated to differentiate SIBO from: 5

• Fungal overgrowth
• Enteric infections
• Graft-versus-host disease (in transplant patients)
• Structural abnormalities (strictures, fistulas) predisposing to SIBO

Common Pitfalls to Avoid

• Do not rely on a negative breath test to exclude SIBO in patients with high clinical suspicion—the sensitivity is too low. 1
• Do not use inflammatory markers like fecal calprotectin to detect SIBO—there is insufficient evidence for this approach. 6
• Do not assume persistent motility dysfunction from a remote viral illness when acid suppression from PPIs is a more likely culprit for SIBO development. 4
• Recognize that lack of response to empirical antibiotics may indicate resistant organisms, absence of SIBO, or presence of other disorders with similar symptoms (bile acid diarrhea, pancreatic insufficiency). 4