Metabolomics of bilharziasis

Abstract

Bilharziasis, a disease that is a major health problem in tropical and subtropical countries, is caused by worms of the genus Schistosoma. The main disease–causing species are S. haematobium, S. mansoni and S. japonicum. Bilharziasis is endemic in South Africa, mostly located in the north–east and covers one quarter of the country, with S. haematobium being the most common species. In this investigation we investigated the schistosome–induced changes in human hosts. We systematically investigated the dynamic metabolic profile of humans infected with S. haematobium using an untargeted gas chromatography's mass spectrometry (GC–MS) metabolomics approach, including univariate and multivariate data analysis. The analysis of host urinary composition is a well suited approach to understand the holistic metabolic responses to infections, since metabolomics is a branch of science concerned with the metabolite composition of biological systems and its dynamic response to both endogenous (i.e. physiology and development) and exogenous (i.e. environmental factors and xenobiotics) stimuli. As a holistic approach, metabonomics detects, quantifies and catalogues metabolic processes of an integrated biological system. In this investigation we selected the organic acid component of the metabolome for the metabolic profiling. Organic acids were determined from urine samples obtained from humans infected with S. haematobium and a control group of non–infected humans. These metabolites were quantified and identified using an automated mass spectral deconvolution and identification system (AMDIS) from which complex two–dimensional data–matrix sets were created, including assessment of the repeatability in generating a metabolomics matrix. Data matrices were analyzed by principal component and partial least square discriminant analyses (PCA and PLS–DA) to investigate which perturbations existed between the two experimental groups. The biochemical interpretation of the information from these analyses indicated that the main biochemical effects of a S. haematobium infection in humans consisted of reduced energy metabolism, liver–function disturbances and perturbations in the gut microbial population common to infections caused by other schistosoma species. Alterations of metabolites of the phenylalanine–tyrosine pathway, including aspects of catecholamine metabolism seems to be novel to a S. haematobium infection and hasn’t been reported in current literature. Finally, proposals were formulated for future investigations on S. haematobium infection.