Metabolite profiling for biomarkers in Schistosoma haematobium infection and associated bladder pathologies

Abstract

BackgroundMetabolic fingerprinting analysis can offer insights into underlying reactions in a biological system; hence it is crucial to the understanding of disease pathogenesis and could provide useful tools for discovering biomarkers. We sought to examine the urine and plasma metabolome in individuals affected by urogenital schistosomiasis and its associated-bladder pathologies.MethodologyBlood and midstream urine were obtained from volunteers who matched our inclusion criteria among residents from Eggua, southwestern Nigeria. Samples were screened by urinalysis, microscopy, PCR and ultrasonography, and categorised as advanced (urogenital schistosomiasis associated-bladder pathologies), infection-only (urogenital schistosomiasis alone) and controls (no infection and no pathology). Metabolites were extracted and data acquired with ultra high-performance liquid chromatography coupled with Thermo Q-Exactive orbitrap HRMS. Data was analysed with MetaboAnalyst, Workflow4Metabolomics, HMDB, LipidMaps and other bioinformatics tools, with univariate and multivariate statistics for metabolite selection.Principal findingsThere were low levels of host sex steroids, and high levels of several benzenoids, catechols and lipids (including ganglioside, phosphatidylcholine and phosphatidylethanolamine), in infection-only and advanced cases (FDR<0.05, VIP>2, delta>2.0). Metabolites involved in biochemical pathways related to chorismate production were abundant in controls, while those related to choline and sphingolipid metabolism were upregulated in advanced cases (FDR<0.05). Some of these human host and Schistosoma haematobium molecules, including catechol estrogens, were good markers to distinguish infection-only and advanced cases.ConclusionsAltered glycerophospholipid and sphingolipid metabolism could be key factors promoting the development of bladder pathologies and tumours during urogenital schistosomiasis.

Alterations of Gut Microbiome and Metabolite Profiling in Mice Infected by Schistosoma japonicum

“…The majority of glycerophospholipids were significantly reduced in response to the infection, such as PC, phosphatidylethanolamine (PE), phosphatidylserine, phosphatidylinositol, and LysoPC. However, the concentration of some PCs was elevated in S. japonicum -infected mice, which was different from the results in S. haematobium -infected patients, where high levels of PC and PE were found ( 70 ). It is believed that the abundance of PC and PE in bladder endothelial cells may be one of the mechanisms for inducing cancer in chronic urogenital schistosomiasis ( 70 ); nevertheless, the different variations presented in PC after S. japonicum infection remain unclear, and future studies should address this question.…”

“…Pathway analysis illuminated that both sphingolipid metabolism and glycerophospholipid metabolism were altered in the process of schistosomiasis, which is consistent with an earlier study of S. haematobium ( 70 ). In fact, sphingolipids and their derivatives have recently presented as promising drug targets for controlling infectious and inflammatory disease; however, how sphingolipid-mediated pathologies and how the host modifies sphingolipid metabolism to benefit itself remain unclear, and a better understanding of these mechanisms may provide new insights into new therapeutic strategies ( 83 ).…”

Bioinformatics evaluation of the homologues ofSchistosoma mansonibiomarker proteins of bladder cancer in otherSchistosomaspecies

“…A modified phosphatidylcholine was also a potential target for an ATP carrier protein (Table 3). This may make biological sense as we previously reported that changes in phosphatidylcholine metabolism was a hallmark of schistosomiasis (Adebayo et al, 2018). The nutraceutical elements are also interesting as they are cheaply available if they do have any benefits.…”

Biomarker discovery and beyond for diagnosis of bladder diseases

“…Other types of omics applications, such as genomics, epigenomics, transcriptomics and metabolomics, were also applied to determine biomarkers of bladder schistosomiasis. Metabolomic profiling using urine and plasma samples revealed that the perturbed glycerophospholipid and sphingolipid metabolisms are associated with schistosomiasis and its associated-bladder cancer pathologies [18]. Epigenetic regulation on RASSF1A and TIMP3 were found using a quantitative methylation-specific PCR assay in urine sediments of patients with schistosomiasis infection.…”