UHPLC-MS-Based Metabolomics Analysis Reveals the Process of Schistosomiasis in Mice

Abstract

Metabolomics, as an emerging technology, has been demonstrated to be a very powerful tool in the study of the host metabolic responses to infections by parasites. Schistosomiasis is a parasitic infection caused by schistosoma worm via the direct contact with the water containing cercaria, among which Schistosoma japonicum ( S. japonicum ) is endemic in Asia. In order to characterize the schistosome-induced changes in the host metabolism and further to develop the strategy for early diagnosis of schistosomiasis, we performed comprehensive LC-MS-based metabolomics analysis of serum from mice infected by S. japonicum for 5 weeks. With the developed diagnosis strategy based on our metabolomics data, we were able to successfully detect schistosomiasis at the first week post-infection, which was 3 weeks earlier than “gold standard” methods and 2 weeks earlier than the methods based on 1 H NMR spectroscopy. Our metabolomics study revealed that S. japonicum infection induced the metabolic changes involved in a variety of metabolic pathways including amino acid metabolism, DNA and RNA biosynthesis, phospholipid metabolism, depression of energy metabolism, glucose uptake and metabolism, and disruption of gut microbiota metabolism. In addition, we identified seventeen specific metabolites whose down-regulated profiles were closely correlated with the time-course of schistosomiasis progression and can also be used as an indicator for the worm-burdens. Interestingly, the decrease of these seventeen metabolites was particularly remarkable at the first week post-infection. Thus, our findings on mechanisms of host-parasite interaction during the disease process pave the way for the development of an early diagnosis tool and provide more insightful understandings of the potential metabolic process associated with schistosomiasis in mice. Furthermore, the diagnosis strategy developed in this work is cost-effective and is superior to other currently used diagnosis methods.

Analysis of Intestinal Microflora and Metabolites From Mice With DSS-Induced IBD Treated With Schistosoma Soluble Egg Antigen

“…Although the pathogenesis of IBD remains to be further explored, most studies believe that IBD is related to immune imbalance ( Nanini et al, 2018 ; Neurath, 2019 ; Mitsialis et al, 2020 ). As a common chronic parasitic worm ( Huang et al, 2016a ; Huang et al, 2016b ; Deol et al, 2019 ), a schistosome develops a variety of mechanisms to manipulate the adaptive immune system of the host while infecting the host ( Huang et al, 2016a ; Huang et al, 2019 ; Huang et al, 2020a ; Huang et al, 2020b ; Buck et al, 2020 ; Zheng et al, 2020 ). Studies have shown that the host immune system gradually shifts from its own invasive T helper 1 (Th1) cell response to anti-inflammatory Th2 cell response 4–6 weeks after cercariae penetrated the skin of the host ( Dunne and Cooke, 2005 ).…”

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

“…Pathogenesis of Schistosoma infection occurs from immunologic reaction of host body to parasite’s eggs, which detection of the disease prior to egg production apparently protect patients from the disease ( McManus et al., 2018 ). In the past few decades, many types of biomolecules have been identified as potential markers, for example, DNA ( Aula et al., 2021 ), proteins ( Zhou et al., 2010 ; Grenfell et al., 2013 ), and metabolites ( Li et al., 2011 ; Huang et al., 2020 ). To date, several attempts have been made to identify metabolite biomarkers at the early stage of schistosomiasis.…”

“…Their data identified phenyl acetyl glycine in urine and 5-aminovalerate in feces as potential markers of infection. Currently, the study by Huang et al (2020) is the only published report to detect S. japonicum infection as early as 1 week postinfection, which is 3 weeks faster than standard methods. This study found 17 serum metabolites from mice that correlated with progression of schistosomiasis, including diphenol glucuronide and glycerol tribenzoate.…”

“…Their data identified phenyl acetyl glycine in urine and 5-aminovalerate in feces as potential markers of infection. Currently, the study by Huang et al. (2020) is the only published report to detect S. japonicum infection as early as 1 week post-infection, which is 3 weeks faster than standard methods.…”

Mining Anti-Inflammation Molecules From Nippostrongylus brasiliensis-Derived Products Through the Metabolomics Approach

“…Mass spectrometry (MS)-based analysis platform makes it possible to identify and quantify small-molecule metabolites from different tissue or body fluid samples, which possibly reflect the health or disease status and provide clues for disease diagnosis and treatment ( Shah et al., 2015 ). For parasite infection, metabolomics analysis has been mostly applied for the discovery of biomarkers and the identification of a new drug target or intervention strategies ( Legido-Quigley, 2010 ; Li et al., 2016 ; Huang et al., 2020 ). However, only very few studies focused on the identification of anti-inflammatory molecules during parasite infection.…”