Metabolomics strategy for diagnosing urinary tract infections

Abstract Metabolomics has emerged as a mainstream approach for investigating complex metabolic phenotypes but has yet to be integrated into routine clinical diagnostics. Metabolomics-based diagnosis of urinary tract infections (UTIs) is a logical application of this technology since microbial waste products are concentrated in the bladder and thus could be suitable markers of infection. We conducted an untargeted metabolomics screen of clinical specimens from patients with suspected UTIs and identified two metabolites, agmatine and N6-methyladenine, that are predictive of culture positive samples. We developed a 3.2-minute LC-MS assay to quantify these metabolites and showed that agmatine and N6-methyladenine correctly identify UTIs caused by 13 Enterobacterales species and 3 non- Enterobacterales species, accounting for over 90% of infections (agmatine AUC > 0.95; N6-methyladenine AUC > 0.89). These markers were robust predictors across two blinded cohorts totaling 1,629 patient samples. These findings demonstrate the potential utility of metabolomics in clinical diagnostics for rapidly detecting UTIs.