Metabonomic investigation of human Schistosoma mansoni infection

Abstract

Schistosomiasis is a parasitic infection that is endemic in many developing countries in the tropics and subtropics afflicting more than 207 million people primarily in rural areas. After malaria, it is the second most important parasitic infection in terms of socio-economic and public health. Investigation of the host-parasite interaction at the molecular level and identification of biomarkers of infection and infection-related morbidity would be of value for improved strategies for treatment and morbidity control. To this end, we conducted a nuclear magnetic resonance (NMR) based metabonomics study involving a well-characterized cohort of 447 individuals from a rural area in Uganda near Lake Victoria with a high prevalence of Schistosoma mansoni, a species predominantly occurring in Africa including Madagascar and parts of South America. Cohort samples were collected from individuals at five time-points, before and after (one or two times) chemotherapy with praziquantel (PZQ). Using supervised multivariate statistical analysis of the recorded one-dimensional (1D) NMR spectra, we were able to discriminate infected from uninfected individuals in two age groups (children and adults) based on differences in their urinary profiles. The potential molecular markers of S. mansoni infection were found to be primarily linked to changes in gut microflora, energy metabolism and liver function. These findings are in agreement with data from earlier studies on S. mansoni infection in experimental animals and thus provide corroborating evidence for the existence of metabolic response specific for this infection.

Advances in the Diagnosis of Human Schistosomiasis

“…Moreover, changes in human urinary biochemical profiles from areas where S. mansoni is endemic have been used to differentiate between infected and uninfected individuals. These findings were important in demonstrating possible changes in human liver function, gut microflora, and energy metabolism due to schistosome infection (260). However, the specificity of these metabo-lites was not assessed, so their use as accurate diagnostic markers has not been determined.…”

Helminth Infections and Gut Microbiota: The Futuristic Study of Pathogen Virulence and Gut Ecosystem

“…Similar changes were also detected in infections by Fasciola hepatica, Necator americanus and other human helminth parasites [16]. Balog et al [17] had reported alterations in the gut microbial communities concomitant with S. mansoni on the basis of urinary response of rodent and human hosts. Li et al [14] could differentiate between infected and uninfected individuals with respect to Schistosoma infection by presence of twelve urinary and five faecal metabolites as biomarkers in infected individuals thereby supporting the hypothesis that S. mansoni alters the host gut microbial activity.…”

“…This alteration manifests itself by the presence of unsusual bacteria [40], greater proportion of common bacteria [40] or by presence of some metabolites in the faeces and/or urine [17]. These may be used as biomarkers for diagnosis of helminth infection that may be utilized for the humans and veterinary animals of economic importance.…”

Sensing parasites: Proteomic and advanced bio-detection alternatives

“…Experimental infections with single or multiple parasite species may allow the discovery of specific or common biomarkers, although they should be further validated in free living populations [15]. To this end, for example it has been shown by serum proteomics of Eimeria sp infected chickens that proteins usually not detected in the blood like those associated with mitochondrial metabolism are good candidates for time-course studies in coccidiosis.…”

“…Therefore, these could be considered as a source for novel diagnostic or prognostic biomarkers [15]. Nowadays, modern -omic technologies are offering high-throughput strategies for such a difficult system biology exploration, with the essential support of novel bioinformatic tools [24,25].…”