Untargeted serum metabolomic profiling for early detection of Schistosoma mekongi infection in mouse model

Abstract

Mekong schistosomiasis is a parasitic disease caused by blood flukes in the Lao People’s Democratic Republic and in Cambodia. The standard method for diagnosis of schistosomiasis is detection of parasite eggs from patient samples. However, this method is not sufficient to detect asymptomatic patients, low egg numbers, or early infection. Therefore, diagnostic methods with higher sensitivity at the early stage of the disease are needed to fill this gap. The aim of this study was to identify potential biomarkers of early schistosomiasis using an untargeted metabolomics approach. Serum of uninfected and S. mekongi-infected mice was collected at 2, 4, and 8 weeks post-infection. Samples were extracted for metabolites and analyzed with a liquid chromatography-tandem mass spectrometer. Metabolites were annotated with the MS-DIAL platform and analyzed with Metaboanalyst bioinformatic tools. Multivariate analysis distinguished between metabolites from the different experimental conditions. Biomarker screening was performed using three methods: correlation coefficient analysis; feature important detection with a random forest algorithm; and receiver operating characteristic (ROC) curve analysis. Three compounds were identified as potential biomarkers at the early stage of the disease: heptadecanoyl ethanolamide; picrotin; and theophylline. The levels of these three compounds changed significantly during early-stage infection, and therefore these molecules may be promising schistosomiasis markers. These findings may help to improve early diagnosis of schistosomiasis, thus reducing the burden on patients and limiting spread of the disease in endemic areas.

Untargeted serum metabolomics analysis of Trichinella spiralis-infected mouse

“…Xanthine and hypoxanthine are molecules that participate in purine metabolism, i.e., the catalysis of hypoxanthine to xanthine and later to uric acid, which induces inflammation through the production of reactive oxygen species [ 44 ]. Interestingly, alterations in xanthine and hypoxanthine levels have been observed in studies of other infectious diseases [ 45 ], especially helminthic infections [ 46 , 47 ]. At 4-weeks PI, the enteric phase diminishes, and larvae embed themselves in striated muscle and other organs of the host, at which point patients show signs of entering the parenteral phase, e.g., muscle pain, periorbital edema, eosinophilia, etc.…”

Serum metabolomic profiles in BALB/c mice induced by Babesia microti infection

“…Several "omics" techniques, such as genomics, proteomics, and transcriptomics, are used to observe host−pathogen interactions (Jean Beltran et al, 2017). Untargeted metabolomics is a powerful approach for investigating host-parasite interactions at the biochemical level and discovering new biomarkers of infection (Chienwichai et al, 2022). LC−MS is commonly used to analyze metabolites and can be used to screen for variations in smallmolecule metabolites in complex biological samples.…”

Identification of trans-genus biomarkers for early diagnosis of intestinal schistosomiasis and progression of gut pathology in a mouse model using metabolomics

“…examined serum metabolomics from S . mekongi -infected mice and identified markers of early Mekong schistosomiasis, for example, heptadecanoyl ethanolamide, picrotin, and theophylline [ 21 ].…”

“…Although metabolomics is an exceptional tool for biomarker discovery, there are a number of issues that previous research did not explore. First of all, all studies identified biomarkers based on infection of only one species [ 18 – 21 ]. A lack of variety in parasite species may hinder the generalization of the discovered markers, especially for intestinal schistosomiasis that caused by 5 species of Schistosoma worms.…”

“…Unfortunately, none of the 4 studies proposed overlapping markers, which supports our earlier statement that elucidating markers for Schistosoma infection in different species may be challenging for the further development of schistosomiasis markers. In addition to the discovery of markers, data from metabolomics can be used to explore disease progression at the different points of time [ 21 , 23 ]. Understanding the progression will provide insight into pathogenesis as well as biology of the parasite.…”