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

Abstract

Background Opisthorchiasis is a hepatobiliary disease caused by flukes of the trematode family Opisthorchiidae. Opisthorchiasis can lead to severe hepatobiliary morbidity and is classified as a carcinogenic agent. Here we investigate the time-resolved metabolic response to Opisthorchis felineus infection in an animal model. Methodology Thirty golden hamsters were divided in three groups: severe infection (50 metacercariae/ hamster), mild infection (15 metacercariae/hamster) and uninfected (vehicle-PBS) groups. Each group consisted of equal number of male and female animals. Plasma samples were collected one day before the infection and then every two weeks up to week 22 after infection. The samples were subjected to 1 H Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate statistical modelling.

Metabolic Homeostasis in Chronic Helminth Infection Is Sustained by Organ-Specific Metabolic Rewiring

“… 22 In our report on the time-resolved metabolomics of serum during O. felineus infection, we observed a strong decrease of the BCAAs during the first weeks of infection. 9 Although the depletion of the circulating BCCAs stabilizes around the 10th week, their levels remain lower than those for the controls during the entire 22 weeks of the experiment. 9 In the current report, the concentration of alanine in the infected animals was lower not only in the liver and spleen, the organs which contribute to the infection signature, but also in serum ( Figure 6 ).…”

“… 9 Although the depletion of the circulating BCCAs stabilizes around the 10th week, their levels remain lower than those for the controls during the entire 22 weeks of the experiment. 9 In the current report, the concentration of alanine in the infected animals was lower not only in the liver and spleen, the organs which contribute to the infection signature, but also in serum ( Figure 6 ). Considering the data on the negative association between helminth infections and the risk of metabolic syndrome, 23 one might be tempted to focus on the similarities between the changes in the systemic metabolism triggered by the chronic O. felineus infection and “protective” metabolic patterns.…”

“… 8 The same applies to serum metabolites and serum lipoprotein clusters: the statistically significant changes in amino acids and lipid clusters were observed in the first weeks after infection. 9 Only few metabolites remained marginally different beyond the 10th week of infection. Thus, the current results and our previous reports show that after the initial state of “metabolic stress” 8 , 9 the organism reaches a state of metabolic homeostasis.…”

“… 9 Only few metabolites remained marginally different beyond the 10th week of infection. Thus, the current results and our previous reports show that after the initial state of “metabolic stress” 8 , 9 the organism reaches a state of metabolic homeostasis. This homeostasis, however, is sustained by a shift in the systemic lipid metabolism and local, organ-specific metabolic adaptive changes.…”

“…This observation is in an agreement both with reports on human material 7 and our recent publication on an animal model. 8 , 9 Indeed, field studies on human body fluids show that the traditional confounding factors such as age, gender, BMI, and lifestyle affect the metabolic composition more strongly than the infection and simply override the effect of the infection. In our animal model report, we have shown that infection-related metabolomic changes in urine are the most pronounced from the 4th week up to the 12th week postinfection.…”