13C urea breath test (UBT) in the diagnosis of Helicobacter pylori: why does it work better with acid test meals?

Abstract

Background: Acid test meals may improve the accuracy of the 13 C urea breath test (UBT). This has been attributed to changes in gastric emptying rather than to the effects of gastric pH on Helicobacter pylori urease. Aims: To determine whether enhancement of 13 CO 2 excretion in the UBT in H pylori infected volunteers by acidification of a test meal is due to a delay in gastric emptying. Methods: Urease activity in vitro was measured in intact bacteria and in bacterial homogenates. Urease activity in vivo was assessed by means of the UBT. Eleven H pylori infected subjects underwent UBTs with neutral Ensure (pH 7.0), acidified Ensure (pH 3.0), and apple juice (pH 3.0). Gastric emptying was assessed by 13 C sodium acetate breath test. Results: From pH 7 to pH 3, the in vitro urease activity of intact bacteria increased sixfold. In contrast, urease activity of bacterial homogenates was inactivated by low pH. In vivo, urease activity, as measured by the UBT 20 minutes after meal ingestion, was higher with apple juice (δ 13 CO 2 =21.1; p=0.03) and acidified Ensure (δ 13 CO 2 =25.5; p=0.01) than with neutral Ensure (δ 13 CO 2 =12.5). Gastric emptying was faster with apple juice (T max =36.7 (8) minutes) but not with acidified Ensure (T max =63.3 (5) minutes; p=0.06) than with neutral Ensure (T max =65.0 (3) minutes; p=0.04). Conclusions: The higher UBT found with acidified compared with neutral test meals was independent of the emptying rates of the test meals but may have been due to medium acidity dependent activation of intra-bacterial urease in intact H pylori.

Helicobacter pyloriDetection and Antimicrobial Susceptibility Testing

“…Indeed, citric acid is able to sensitize the test not only by delaying gastric emptying but by a direct effect on intragastric urease activity, possibly on UreI, a proton-gated urea channel, making urea more accessible to the intrabacterial urease (499). Similar results have been found in another study where urease activity increased sixfold between pH 7 and pH 3 (431). Whether the enhanced H. pylori urease activity in vivo is strictly pH dependent or not is still a matter of debate.…”

Masking of 13C urea breath test by proton pump inhibitors is dependent on type of medication: comparison between omeprazole, pantoprazole, lansoprazole and esomeprazole

“…Inhibition of the bacterial urease activity secondary to alkalinization of the gastric content is one of the possible explanations for the false negative UBT induced by PPIs. [20][21][22][23] Both urease activity and the transport of urea into the bacteria which is regulated by UreI-dependent specific H+-gated urea channels are pH dependent. 24 Urease activity is low at neutral pH, but as the external pH decreases to between 6.5 and 5.5 there is a 10-20-fold increase in activity which remains high through approximately pH 2.5.…”

Low Dose Capsule Based 13c-Urea Breath Test Compared With the Conventional 13c-Urea Breath Test and Invasive Tests

“…In this study powdered orange juice (pH = 3.0) was taken with the capsule to increase sensitivity of the test, although citric acid as excipient of the capsule formulation may provide an acidic microenvironment. The activity of bacterial urease and the 13 CO 2 excretion were significantly higher with apple juice (pH = 3.0) or with acidified meal (pH = 3.0) than with neutral meal, and independent of gastric emptying (26) . Other authors (7,13,27) that tested 50 and or 100 mg capsule of 13 C-urea with water, showed sensitivity of 95%-100% and specificity of 97.6%-100%, suggesting that acid test meal may be omitted, lowering the cost of the exam.…”