Stool microbiome reveals diverse bacterial ureases as confounders of oral urea breath testing for Helicobacter pylori and Mycobacterium tuberculosis in Bamako, Mali

Abstract

Detection of bacterial urease activity has been utilized successfully to diagnose Helicobacter pylori (H. pylori). While Mycobacterium tuberculosis (M. tb) also possesses an active urease, it is unknown whether detection of mycobacterial urease activity by oral urease breath test (UBT) can be exploited as a rapid point of care biomarker for tuberculosis (TB) in humans. We enrolled 34 individuals newly diagnosed with pulmonary TB and 46 healthy subjects in Bamako, Mali and performed oral UBT, mycobacterial sputum culture and H. pylori testing. Oral UBT had a sensitivity and specificity (95% CI) of 70% (46–88%) and 11% (3–26%), respectively, to diagnose culture-confirmed M. tb disease among patients without H. pylori, and 100% sensitivity (69–100%) and 11% specificity (3–26%) to diagnose H. pylori among patients without pulmonary TB. Stool microbiome analysis of controls without TB or H. pylori but with positive oral UBT detected high levels of non-H. pylori urease producing organisms, which likely explains the low specificity of oral UBT in this setting and in other reports of oral UBT studies in Africa.

Pre-existing Helicobacter pylori serum IgG enhances the vibriocidal antibody response to CVD 103-HgR live oral cholera vaccine in Malian adults

“…However, it is well documented that H. pylori infection is mostly acquired in childhood and persists throughout adulthood 19,20 . Moreover, use of a serological assay in this setting in Mali might be the best tool in terms of specificity given reports of potential misclassification due to non-H. pylori urease-producing bacteria identified by urea breath test 67 .…”

Diagnosis of tuberculosis through breath test: A systematic review

“…Five studies only included subjects representing two extreme sides of the clinical spectrum of TB disease (healthy controls without any TB symptoms, and symptomatic, treatment-naïve, smear positive pulmonary TB cases) [18,21,[36], [37], [38]]. Meanwhile, different stages of TB disease are characterized by dynamic metabolic changes within pathogen and host and their interactions, thus different stages of TB disease may generate different breath test results [21].…”

“…To validate the biomarkers that were found through GC–MS or other spectrometries, a large cohort study is needed. The use of oral urea administration in diagnosing TB may not be ideal because of low lung concentration, and is confounded by the presence of H. pylori in the gut [38]. However, the administration of urea by inhalation for diagnosing TB warrants investigation.…”

Diagnosis of Helicobacter pylori infection

“…The problem is to avoid detection of H. pylori urease which can be solved either by injecting 13 C‐urea or by suppressing H. pylori with PPI. This procedure was used in Mali but lacked specificity because of other urease positive components of the gut microbiota …”

“…This procedure was used in Mali but lacked specificity because of other urease positive components of the gut microbiota. 45 By combining 13 C-UBT and glucose hydrogen/methane breath test (HMBT), H. pylori infection was shown to be significantly associated with the presence of small intestine bacterial overgrowth (SIBO). 46 Interestingly, some authors utilized the natural 13 C-and 18 O-urea normally present in human gastric juice by isotopic fractionation of breath CO 2 and tried to link the results to the disease status (PUD vs NUD) but more work still has to be carried out.…”