Quantitative metabolomics of urine for rapid etiological diagnosis of urinary tract infection: evaluation of a microbial-mammalian co-metabolite as a diagnostic biomarker

Background: We have previously reported a NMR-based urinalysis for the screening of urinary tract infection (UTI) with high accuracy and reproducibility. Urinary acetic acid per creatinine was found to be a diagnostic marker of bacterial UTI with an area-under-receiver operating characteristic (ROC) curve of 0.97. In addition, we identified trimethylamine (TMA) as a human-microbial marker of Escherichia coli (EC)-associated UTI. Here, we evaluate the clinical application of NMR-based urinalysis in aiding the etiological diagnosis of bacterial UTI.

Methods: Proton NMR spectroscopy was acquired using a Bruker 600MHz spectroscopy for 88 urine samples from patients with bacterial UTI, confirmed by urine culture. The spectra were analyzed using orthogonal partial least squares-discriminant analysis (OPLS-DA). ROC curve analysis was performed after the quantitation of the urine metabolites.

Results: The TMA/creatinine (mmol/mmol) level was determined to be a specific marker for EC-associated UTI. It has an area-under-ROC=0.85 (95% confidence interval: 0.75-0.91). For the etiological diagnosis, the cutoff for 97.0% specificity was at 0.0117mmol/mmol creatinine for EC-associated UTI with a sensitivity of 66.7%. The mean of TMA/creatinine of EC is 21-fold that of non-EC.

Conclusions: The co-metabolism of TMA by EC and human cells makes TMA an ideal urine biomarker for UTI. The presence of TMA in a freshly collected sample eliminates the possibility of contamination of urine by bacteria during the collection process resulting in a positive bacterial culture result. We envisage the NMR-based urinalysis of urinary TMA that can be a useful method for the etiological diagnosis of EC-associated UTI.