Exploratory metabolomics study of the experimental opisthorchiasis in a laboratory animal model (golden hamster, Mesocricetus auratus)

Abstract

BackgroundOpisthorchiasis is a parasitic infection caused by the liver flukes of the Opisthorchiidae family. Both experimental and epidemiological data strongly support a role of these parasites in the etiology of the hepatobiliary pathologies and an increased risk of intrahepatic cholangiocarcinoma. Understanding a functional link between the infection and hepatobiliary pathologies requires a detailed description a host-parasite interaction on different levels of biological regulation including the metabolic response on the infection. The last one, however, remains practically undocumented. Here we are describing a host response on Opisthorchiidae infection using a metabolomics approach and present the first exploratory metabolomics study of an experimental model of O. felineus infection.Methodology and Principal findingsWe conducted a Nuclear Magnetic Resonance (NMR) based longitudinal metabolomics study involving a cohort of 30 animals with two degrees of infection and a control group. An exploratory analysis shows that the most noticeable trend (30% of total variance) in the data was related to the gender differences. Therefore further analysis was done of each gender group separately applying a multivariate extension of the ANOVA—ASCA (ANOVA simultaneous component analysis). We show that in the males the infection specific time trends are present in the main component (43.5% variance), while in the females it is presented only in the second component and covers 24% of the variance. We have selected and annotated 24 metabolites associated with the observed effects and provided a physiological interpretation of the findings.ConclusionsThe first exploratory metabolomics study an experimental model of O. felineus infection is presented. Our data show that at early stage of infection a response of an organism unfolds in a gender specific manner. Also main physiological mechanisms affected appear rather nonspecific (a status of the metabolic stress) the data provides a set of the hypothesis for a search of the more specific metabolic markers of the Opisthorchiidae infection.

Plasma metabolomics of the time resolved response to Opisthorchis felineus infection in an animal model (golden hamster, Mesocricetus auratus)

“…After collection into individually labelled Eppendorf tubes, all samples were transferred to a freezer (-80˚C) for long term storage. The worm burden and egg output were described in details in the first part of the exploratory metabolomics of the experimental opisthorchiasis in a golden hamster [15].…”

“…The method of calculation of the number of eggs per gram of feces and the estimation of the worm burden were described in the urinary NMR-based metabolomics study of experimental opisthorchiasis in the golden hamster (Mesocricetus auratus) [15].…”

“…The worm burden and egg output were described in detail in the first part of the exploratory metabolomics of opisthorchiasis in the golden hamster [15]. To get an overview of the main sources of variance in the data we used principal component analysis (PCA).…”

“…To fill the existing data gap, we concentrate on a comprehensive description of the timeresolved response of the host on the O. felineus infection using metabolomics. The first part was dedicated to the metabolic changes detected in the urine samples [15], the current work covers the infection-dependent changes in the blood plasma samples. The study was designed as a longitudinal study with two degrees of the infection intensity.…”

Biliary microbiota and bile acids composition in cholelithiasis

“…Gender doesn't provide significant input in microbial community structure (p=0.156). [18]. Thus, to investigate a role of the infection status on BAs composition in gallbladder disease we analyzed the measured BAs with respect to the infection status of the patients.…”