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Diagnosing pneumonia with urinary metabolomics
my knowledge, very few studies have achieved this using large sample numbers and, therefore, sturdy chemometIn the fourth century B.C., the Greek rics models.” physician Hippocrates correlated urine When the investigators conducted a characteristics such as color and sediblinded analysis of an independent ment with specific illnesses. Today, sample set of 145 urine samples from sensitive analytical techniques allow healthy individuals or patients with researchers to study how the profile of various conditions, metabolic profiling urinary metabolites changes in reenabled sensitive (86%) and specific sponse to disease. To develop a urinary (94%) diagnosis of pneudiagnostic test for pneumococcal pneumonia. mococcal pneumonia, “The specificity and sensiCarolyn Slupsky, now at tivity of the models for the the University of Califordetection of S. pneumonia nia Davis, and colleagues show great promise for at the University of Alrapid NMR-based diagnosberta, the University of tics,” says Gil. Toronto (both in Canada), By analyzing urine and Austin Health (Austrasamples collected at varilia) profiled metabolites in ous intervals during hospipatient urine. They report talization, Slupsky and coltheir results in a new JPR leagues could “actually paper (2009,10.1021/ observe the sick patients pr9006427). moving back to what we According to Sunil would consider a normal Kochhar at the Nestle´ Remetabotype,” she says. search Center (Switzer“This could be very useful land), “The application of The path to wellness. As three patients (purple, green, and yellow for monitoring therapy. A metabolic profiling in distrajectories) recovered from pneumococcal pneumonia, their metabolite profiles doctor could determine ease diagnostics is highly returned to normal. Metabolite profiles of control subjects (filled squares) are very soon whether a partopical, especially in disstatistically distinct from those of pneumococcal pneumonia patients (open ticular drug administered eases where there are no circles). to the patient is being robust diagnostics availhelpful or harmful.” able.” Such is the case for principal components analysis and orThe sensitive, quantitative nature of pneumococcal pneumonia, an infecthogonal partial least squares-discrimithe metabolomics approach might altion of the lungs caused by the bactenant analysis. The results showed a low doctors to detect aberrant metarium Streptococcus pneumoniae. The clear distinction between the metabobolic profiles at relatively early stages symptoms of pneumococcal pneumolomes of S. pneumoniae-infected and of disease, and in that case, “only a nia are similar to those of pneumonia uninfected individuals. Furthermore, mild treatment might be needed for caused by other microbes and those of the urinary metabolic profiles of pafull recovery, rather than giving a some unrelated respiratory conditions, tients with pneumococcal pneumonia 7-day-or-more, broad-based antibiotic and blood and sputum cultures often varied substantially from those of treatment,” Kochhar notes. But he says fail to detect S. pneumoniae. people with pneumonia caused by vithat for the metabolite profile of S. “In talking with clinicians, I learned ruses or by other species of bacteria. pneumoniae infection to become a rothat fewer than 20% of patients who The pneumococcal pneumonia mebust diagnostic tool, “further studies are hospitalized for pneumonia are aptabolome also was significantly differare needed in different populations propriately diagnosed,” says Slupsky. ent from the metabolomes of patients and age groups under different dietary As a result, many patients are treated under conditions of metabolic stress, regimes.” with the wrong antibiotic or with liver dysfunction, pulmonary disease, In addition to possibly yielding imbroad-based antibiotics, which can deand fasting. proved diagnostic methods, the S. lay recovery and contribute to the “The results demonstrate that uripneumoniae metabolomic data should problem of microbial antibiotic resisnary metabolic signatures may indeed provide insights into the complex intance. To investigate whether pneumobe sufficiently specific for a certain disteractions between the bacterium and coccal pneumonia could be sensitively ease, even within diseases of similar host, says Slupsky. “We were surprised and specifically detected from urine, origins or symptoms,” says Ana Gil at that most of the metabolites that Slupsky and co-workers compared the the University of Aveiro (Portugal). “To changed significantly with S. pneumourinary metabolomes of healthy indi-
10.1021/pr9009832
viduals, patients with various types of pneumonia, and patients with noninfectious conditions that can mimic pneumonia (for example, congestive heart failure). The researchers quantitatively measured 61 metabolites in urine samples with NMR spectroscopy and then compared the metabolic profiles by using two types of multivariate data analysis,
© 2009 American Chemical Society
Journal of Proteome Research • Vol. 8, No. 12, 2009 5409
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niae infection were related to the host response to infection, rather than being produced by the pathogen,” she remarks. “For future studies, we’re interested in understanding how mi-
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crobes interact with the host, and how these interactions modulate specific metabolic pathways to create unique metabolite profiles.” These studies could help explain why some people
Journal of Proteome Research • Vol. 8, No. 12, 2009
get more or less severe forms of an infectious disease, as well as assist physicians in tailoring individualized therapies. —Laura Cassiday
10.1021/pr9009832
© 2009 American Chemical Society
