Comparative Metabonomic Investigations of Schistosoma japonicum From SCID Mice and BALB/c Mice: Clues to Developmental Abnormality of Schistosome in the Immunodeficient Host

Abstract

The growth and development of schistosome has been affected in the immunodeficient hosts. But it remains unresolved about the molecular mechanisms involved in the development and reproduction regulation of schistosomes. This study tested and compared the metabolic profiles of the male and female Schistosoma japonicum worms collected from SCID mice and BALB/c mice at 5 weeks post infection using liquid chromatography tandem mass spectrometry (LC-MS/MS) platform, in which the worms from SCID mice were the investigated organisms and the worms from BALB/c mice were used as the controls. There were 1015 ion features in ESI+ mode and 342 ion features in ESI- mode were identified after filtration by false discovery rate. Distinct metabolic profiles were found to clearly differentiate both male and female worms in SCID mice from those in BALB/c mice using multivariate modeling methods including the Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). There were more differential metabolites in female worms than in male worms between SCID mice and BALB/c mice. And common and uniquely perturbed metabolites and pathways were identified among male and female worms from SCID mice when compared with BALB/c mice. The enriched metabolite sets of the differential metabolites in male worms between SCID mice and BALB/c mice included bile acid biosynthesis, taurine and hypotaurine metabolism, sphingolipid metabolism, retinol metabolism, purine metabolism, etc. And the enriched metabolite sets of differential metabolites in female worms included retinol metabolism, alpha linolenic acid and linoleic acid metabolism, purine metabolism, sphingolipid metabolism, glutamate metabolism, etc. Further detection and comparison in transcript abundance of genes of the perturbed retinol metabolism and its associated meiosis process in worms identified clues suggesting accumulated retinyl ester and perturbed meiotic process. These findings suggested an association between the schistosome with retarded growth and development in SCID mice and their perturbed metabolites and metabolic pathways, and provided a new insight into the growth and development regulation of S. japonicum worms from the metabolic level, which indicated great clues for discovery of drugs or vaccines against the parasites and disease with more researches.

Schistosoma haematobium infection is associated with alterations in energy and purine-related metabolism in preschool-aged children

“…Metabolic pathway analysis showed that the increases were related to energy (glycolysis, PPP, starch, and galactose) and purine metabolism. This is consistent with findings from studies conducted in experimental models of schistosome infection [34,36,86], showing that such host metabolic alterations from schistosome infection begin as early as three weeks post-infection [19].…”

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

“…It cannot be ignored that some sphingomyelin (SM) species were reduced after infection, while the concentration of ceramide (Cer) was elevated, especially at the late stage of infection; the variation trend of SM and Cer was also observed in T. b. rhodesiense human African trypanosomiasis patients ( 16 ). Sphingolipids not only are components of the membrane that are able to protect the cell from harmful environmental factors but also are involved in cellular signaling as a second messenger ( 77 , 78 ); the significant observations in sphingolipids (SM and Cer) may offer the basis and foundation for revealing the resistance mechanism between hosts and S. japonicum since infection can trigger the generation of Cer, which is generated in part by sphingomyelinase enzymes, leading to cell autophagy and apoptosis, additional pro-inflammatory cytokines, and chemokine synthesis, as well as other metabolic disorders ( 16 , 79 , 80 ). It is more interesting to note that the metagenomic analysis revealed that the chemokine signaling pathway was upregulated at 42 dpi, which suggests that inflammatory effects existed in gut bacteria also; the host and the gut microbiota collaborate with each other to eliminate the parasites.…”

Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel

“…In S . japonicum , retinol metabolism is associated with meiosis processes and the growth of worms [ 63 ]; therefore, the downregulation of retinol metabolism by PZQ treatment may inhibit egg production and reduce the growth of S . mekongi .…”