What is the preferred substrate, lactulose or glucose, for the Small Intestine Bacterial Overgrowth (SIBO) breath test in terms of accuracy?

From the Guidelines

Glucose is recommended over lactulose for the Small Intestine Bacterial Overgrowth (SIBO) breath test due to its higher specificity, despite lactulose's ability to detect distal SIBO. The choice of substrate for SIBO breath testing is crucial for accurate diagnosis. While lactulose is often considered due to its ability to travel the entire length of the small bowel and detect distal SIBO, its use is associated with a higher false-positive rate due to rapid transit time in some patients, causing colonic fermentation to be misinterpreted as SIBO 1. On the other hand, glucose, although rapidly absorbed in the proximal small intestine, has been found to have a higher specificity in some studies, making it a preferable choice for SIBO diagnosis 1.

Key Considerations

• The sensitivity and specificity of breath tests for SIBO diagnosis are generally poor, with hydrogen breath testing having limitations due to variations in bacterial flora and orocaecal transit times 1.
• Glucose breath testing has been shown to have a sensitivity less than 50% compared with duodenal aspirate, regardless of whether or not methane measurement is added to hydrogen 1.
• Lactulose-hydrogen breath tests have sensitivities ranging from 17% to 68%, with specificities around 70% 1.
• The choice between glucose and lactulose should consider the clinical context and the potential for false positives or negatives, prioritizing the substrate that best balances these factors for the individual patient.

Clinical Implications

• In clinical practice, the selection of glucose or lactulose for SIBO breath testing should be guided by the most recent and highest quality evidence available, currently suggesting glucose as a preferable option due to its specificity 1.
• However, lactulose's ability to detect distal SIBO should not be overlooked, and its use may be justified in certain clinical scenarios where distal SIBO is suspected and the benefits of its use outweigh the risks of false positives.
• Ultimately, the diagnosis of SIBO should be made considering a combination of clinical presentation, diagnostic test results, and response to treatment, rather than relying solely on breath test findings.

From the Research

Accuracy of SIBO Breath Test: Lactulose versus Glucose

The accuracy of the Small Intestine Bacterial Overgrowth (SIBO) breath test depends on various factors, including the substrate used. Two commonly used substrates are lactulose and glucose.

• Substrate Preference: According to a study published in 2014 2, glucose arguably provides greater testing accuracy than lactulose for SIBO diagnosis.
• Comparison of Substrates: A 2024 study 3 compared the diagnostic value of lactulose and glucose breath tests with jejunal aspiration cultures. The results showed that the glucose breath test (GBT) had good agreement (κ = 0.659) with the jejunal aspirate culture, while the lactulose breath test (LBT) had poor agreement (κ = 0.588).
• Sensitivity and Specificity: The same study 3 found that GBT was more specific than LBT, but had a lower sensitivity. The sensitivity and specificity of LBT were 85.7% and 76.9%, respectively, while those of GBT were 71.4% and 92.3%, respectively.
• North American Consensus Guidelines: A 2017 consensus statement 4 recommended the use of glucose and lactulose breath tests for SIBO diagnosis, with a rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose breath test considered positive.
• Performance and Interpretation: A 2022 study 5 evaluated the performance and interpretation of hydrogen and methane breath testing using the North American Consensus guidelines. The results showed that 10 g lactulose significantly reduced positive SIBO results compared to 16 g lactulose, while 75 g glucose significantly increased positive results compared to 50 g glucose.
• Comparison of Lactulose and Glucose Breath Tests: A 2012 study 6 compared the lactulose and glucose breath tests for SIBO diagnosis in patients with irritable bowel syndrome. The results showed that the glucose breath test was more accurate than the lactulose breath test, with a sensitivity of 63.6% and specificity of 67.7% for the lactulose breath test.