Diagnosis of small intestinal bacterial overgrowth in irritable bowel syndrome patients using high-precision stable 13CO2/12CO2 isotope ratios in exhaled breath

Hydrogen breath tests (HBT) are widely used for the diagnosis of small intestinal bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS). However, the conclusions drawn from these studies are highly controversial, and several discrepancies exist in the results. The aim of our study is to develop an alternative C-13-glucose breath test (C-13-GBT) methodology by measuring high-precision (CO2)-C-13/(CO2)-C-12 isotope ratios in exhaled breath to accurately diagnose SIBO using an optical cavity-enhanced CO2 isotope analyzer. In all, 118 diarrhea-predominant (IBS-D) patients diagnosed according to ROME III criteria underwent C-13-GBT and HBT following the ingestion of a test meal containing 50 mg C-13-enriched glucose with 50 g glucose. The excretion of (CO2)-C-13 enrichments and a cumulative percentage dose of C-13-recovered (c-PDR) significantly depleted (p < 0.001) for the positive SIBO patients (n = 25) compared to the patients with negative SIBO (n = 53) as diagnosed by HBT. A cut-off value of 5.47 parts per thousand at 45 min was indicative of a positive SIBO syndrome. Subsequently, a portion of IBS-D individuals (n = 20) whose HBTs were negative but C-13-GBTs were positive, suggesting HBT often fails to diagnose SIBO when the patients may have "non-hydrogen-producing" bacteria. C-13-GBT also correctly diagnosed SIBO in patients (n = 20) within the "grey-zone" and during the preclinical phase of SIBO as opposed to HBT. The prevalence of SIBO with IBS-D in Indian population was estimated to be 45.7%. Our study demonstrates C-13-GBT, for the first time, as a clinically valid and sufficiently robust alternative diagnostic methodology for an accurate evaluation of SIBO in IBS-D patients and superior to HBT.