Metabonomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification. Export

@article{wang04, abstract = {Schistosomiasis, a chronic and debilitating parasitic disease, affects approximately 200 million people in the developing world and imposes a substantial public health and economic impact. Accurately diagnosing at the individual level, monitoring disease progression, and assessing the impact of pharmacological interventions at the population level are of prime importance for controlling schistosomiasis. Using a Schistosoma mansoni-mouse model, we present a characterization of a parasitic infection by metabolic profiling, employing (1)H NMR spectroscopy and multivariate pattern recognition techniques. We infected 10 mice with 80 S. mansoni cercariae each and collected urine samples 49 and 56 days postinfection. Urine samples were also obtained from 10 uninfected control mice at the same time. The metabolic signature of an S. mansoni infection consists of reduced levels of the tricarboxylic acid cycle intermediates, including citrate, succinate, and 2-oxoglutarate, and increased levels of pyruvate, suggesting stimulated glycolysis. A disturbance of amino acid metabolism was also associated with an S. mansoni infection, as indicated by depletion of taurine, 2-oxoisocaproate, and 2-oxoisovalerate and elevation of tryptophan in the urine. A range of microbial-related metabolites, i.e., trimethylamine, phenylacetylglycine, acetate, p-cresol glucuronide, butyrate, propionate, and hippurate, were also coupled with an S. mansoni infection, indicating disturbances in the gut microbiota. Our work highlights the potential of metabolic profiling to enhance our understanding of biological responses to parasitic infections. It also holds promise as a basis for novel diagnostic tests with high sensitivity and specificity and for improved disease surveillance and control.}, author = {Wang, Yulan and Holmes, Elaine and Nicholson, Jeremy K. and Cloarec, Olivier and Chollet, Jacques and Tanner, Marcel and Singer, Burton H. and Utzinger, J\"{u}rg}, citeulike-article-id = {5916134}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0404878101}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15314235}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15314235}, day = {24}, doi = {10.1073/pnas.0404878101}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {biomarker, nmr, nmr\_moltwin}, month = {August}, number = {34}, pages = {12676--12681}, posted-at = {2009-10-09 14:39:34}, priority = {2}, title = {Metabonomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification.}, url = {http://dx.doi.org/10.1073/pnas.0404878101}, volume = {101}, year = {2004} }

TY - JOUR ID - wang04 L3 - citeulike-article-id:5916134 N2 - Schistosomiasis, a chronic and debilitating parasitic disease, affects approximately 200 million people in the developing world and imposes a substantial public health and economic impact. Accurately diagnosing at the individual level, monitoring disease progression, and assessing the impact of pharmacological interventions at the population level are of prime importance for controlling schistosomiasis. Using a Schistosoma mansoni-mouse model, we present a characterization of a parasitic infection by metabolic profiling, employing (1)H NMR spectroscopy and multivariate pattern recognition techniques. We infected 10 mice with 80 S. mansoni cercariae each and collected urine samples 49 and 56 days postinfection. Urine samples were also obtained from 10 uninfected control mice at the same time. The metabolic signature of an S. mansoni infection consists of reduced levels of the tricarboxylic acid cycle intermediates, including citrate, succinate, and 2-oxoglutarate, and increased levels of pyruvate, suggesting stimulated glycolysis. A disturbance of amino acid metabolism was also associated with an S. mansoni infection, as indicated by depletion of taurine, 2-oxoisocaproate, and 2-oxoisovalerate and elevation of tryptophan in the urine. A range of microbial-related metabolites, i.e., trimethylamine, phenylacetylglycine, acetate, p-cresol glucuronide, butyrate, propionate, and hippurate, were also coupled with an S. mansoni infection, indicating disturbances in the gut microbiota. Our work highlights the potential of metabolic profiling to enhance our understanding of biological responses to parasitic infections. It also holds promise as a basis for novel diagnostic tests with high sensitivity and specificity and for improved disease surveillance and control. IS - 34 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 0027-8424 EP - 12681 TI - Metabonomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification. VL - 101 SP - 12676 KW - biomarker KW - nmr KW - nmr_moltwin AU - Wang, Yulan AU - Holmes, Elaine AU - Nicholson, Jeremy AU - Cloarec, Olivier AU - Chollet, Jacques AU - Tanner, Marcel AU - Singer, Burton AU - Utzinger, Jürg PY - 2004/08/24/ UR - http://dx.doi.org/10.1073/pnas.0404878101 ER -