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

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          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 1H 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.

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          Most cited references49

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          Advances in the Diagnosis of Human Schistosomiasis.

          Schistosomiasis is a major neglected tropical disease that afflicts more than 240 million people, including many children and young adults, in the tropics and subtropics. The disease is characterized by chronic infections with significant residual morbidity and is of considerable public health importance, with substantial socioeconomic impacts on impoverished communities. Morbidity reduction and eventual elimination through integrated intervention measures are the focuses of current schistosomiasis control programs. Precise diagnosis of schistosome infections, in both mammalian and snail intermediate hosts, will play a pivotal role in achieving these goals. Nevertheless, despite extensive efforts over several decades, the search for sensitive and specific diagnostics for schistosomiasis is ongoing. Here we review the area, paying attention to earlier approaches but emphasizing recent developments in the search for new diagnostics for schistosomiasis with practical applications in the research laboratory, the clinic, and the field. Careful and rigorous validation of these assays and their cost-effectiveness will be needed, however, prior to their adoption in support of policy decisions for national public health programs aimed at the control and elimination of schistosomiasis.
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            Gut Microbial Metabolites of Aromatic Amino Acids as Signals in Host–Microbe Interplay

            Gut microbial metabolism is intimately coupled with host health and disease. Aromatic amino acid (AAA) catabolism by the gut microbiome yields numerous metabolites that may regulate immune, metabolic, and neuronal responses at local and distant sites. Such a chemical dialog between host cells and the gut microbiome is shaped by environmental cues, and may become dysregulated in gastrointestinal and systems diseases. Increasing knowledge of the bacterial pathway and signaling basis may shed additional light on metabolic host-microbiome crosstalk that remains untapped for drug discovery. Here, we update our understanding of microbial AAA metabolism and its impacts on host physiology and disease. We also consider open questions related to therapeutically mining these signaling metabolites and how recent concepts and tools may drive this area forward.
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              Relative contribution of day-to-day and intra-specimen variation in faecal egg counts of Schistosoma mansoni before and after treatment with praziquantel.

              There is evidence that faecal egg counts of Schistosoma mansoni vary considerably from day to day, which results in poor sensitivity of single stool readings. Intra-specimen variation of S. mansoni egg counts may also be considerable, but has previously been considered as the less important component. We quantified the relative contribution of these two sources of variation among 96 schoolchildren from an area in Cĵte d'Ivoire highly endemic for S. mansoni. Stool specimens were collected over 5 consecutive days, and 5 egg-counts were made in each specimen by the Kato-Katz technique. The point prevalence of the first sample was 42.7% and the cumulative prevalence after the maximum sampling effort was 88.5%. Using generalized linear mixed models we found that the presence of S. mansoni eggs in a stool sample varied much more between days than within specimens, indicating that stool sample examination over multiple days is required for accurate prevalence estimates. However, using the same approach, we found that among infected children intra-specimen variation in egg counts was 4.3 times higher than day-to-day variation. After praziquantel administration, day-to-day variation was more important than before, since most infections were very light and thus likely to be missed altogether by stool examination on a single day. We conclude that diagnostic sensitivity in high transmission areas is maximized by making several stool readings on several days, but examining 1 stool specimen several times can make reasonable estimates of infection intensity.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                14 July 2020
                2020
                : 11
                : 1517
                Affiliations
                [1] 1National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases , Wuxi, China
                [2] 2Center for Global Health, School of Public Health, Nanjing Medical University , Nanjing, China
                [3] 3Public Health Research Center, Jiangnan University , Wuxi, China
                [4] 4Department of Pharmacy, General Hospital of Southern Theater Command , Guangzhou, China
                [5] 5Bloomberg-Kimmel Institute for Cancer Immunotherapy, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore, MD, United States
                [6] 6School of Medicine, Shanghai University , Shanghai, China
                [7] 7Institute of Translation Medicine, Shanghai University , Shanghai, China
                [8] 8Department of Pharmacy, Changzheng Hospital, Second Military Medical University , Shanghai, China
                Author notes

                Edited by: Michael Harrison Hsieh, Children’s National Hospital, United States

                Reviewed by: Malcolm Jones, The University of Queensland, Australia; Patrick Skelly, Tufts University, United States

                *Correspondence: Jun Cao, caojuncn@ 123456hotmail.com

                These authors have contributed equally to this work

                This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2020.01517
                7371968
                32760365
                4046eff3-4dfe-457f-8c8f-76febe977d8d
                Copyright © 2020 Huang, Wu, Zhao, Xiong, Xu, Dong, Wen and Cao.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 December 2019
                : 11 June 2020
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 53, Pages: 14, Words: 0
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                uhplc-ms,metabolomics,schistosomiasis,early diagnosis,serum
                Microbiology & Virology
                uhplc-ms, metabolomics, schistosomiasis, early diagnosis, serum

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