Metabolic Profiling of an Echinostoma caproni Infection in the Mouse for Biomarker Discovery

Consumption of raw fish and other freshwater products can lead to unpleasant worm infections. Indeed, such worm infections are of growing public health and veterinary concern, but they are often neglected, partially explained by the difficulty of accurate diagnosis. In the present study we infected 12 mice with an intestinal worm (i.e., Echinostoma caproni) and collected blood, stool, and urine samples 7 times between 1 and 33 days after the infection. At the same time points, blood, stool, and urine were also sampled from 12 uninfected mice. These biofluid samples were examined with a spectrometer and data were analyzed with a multivariate approach. We observed important differences between the infected and the uninfected control animals. For example, we found an increased level of branched chain amino acids in the stool of infected mice and subsequent depletion in blood plasma. Additionally, we observed changes related to a disturbed intestinal bacterial composition, particularly in urine and stool. The combination of results from the three types of biofluids gave the most comprehensive characterization of an E. caproni infection in the mouse. Urine would be the biofluid of choice for diagnosis of an infection because the ease of sample collection and the high number and extent of changed metabolites

Biomarkers, metabonomics, and drug development: Can inborn errors of metabolism help in understanding drug toxicity?

Application of “omics” technology during drug discovery and development is rapidly evolving. This review evaluates the current status and future role of “metabonomics” as a tool in the drug development process to reduce the safety-related attrition rates and bridge the gaps between preclinical and clinical, and clinical and market. Particularly, the review looks at the knowledge gap between the pharmaceutical industry and pediatric hospitals, where metabonomics has been successfully applied to screen and treat newborn babies with inborn errors of metabolism. An attempt has been made to relate the clinical pathology associated with inborn errors of metabolism with those of drug-induced pathology. It is proposed that extending the metabonomic biomarkers used in pediatric hospitals, as “advanced clinical chemistry” for preclinical and clinical drug development, is immediately warranted for better safety assessment of drug candidates. The latest advances in mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy should help replace the traditional approaches of laboratory clinical chemistry and move the safety evaluation of drug candidates into the new millennium