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      Characterization of the Blood and Cerebrospinal Fluid Microbiome in Children with Bacterial Meningitis and Its Potential Correlation with Inflammation

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          ABSTRACT

          Bacterial meningitis shows a higher incidence in children than adults, but signs may be scarce. Although some pathogenic microorganisms of meningitis from cerebrospinal fluid (CSF) have been reported, the signature of the representative microbiota in CSF and blood samples from patients remains incompletely revealed. To extend the understanding of the microbiome in patients, we recruited 32 children with bacterial meningitis, 30 undiagnosed infectious children, and 10 matched healthy individuals, which was followed by untargeted metagenomic next-generation sequencing (mNGS) and bioinformatic analysis. Our results showed that children with bacterial meningitis exhibited different microbiome signatures in their CSF and blood compared with undiagnosed and healthy children, and patients could be divided into varied subsets according to these signatures, including Escherichia coli, Klebsiella pneumoniae, Thermothelomyces thermophila, Lactobacillus acidophilus, and Staphylococcus haemolyticus. To further explore their potential role in patients’ conditions, we examined their correlation with clinical parameters. Importantly, microbiome signatures with compositional changes were correlated with the C-reactive protein (CRP) level in blood and granulocyte percentage in CSF. Moreover, the blood in subsets of patients with a predominance of Klebsiella pneumoniae could replace CSF as the main specimen for clinical monitoring.

          IMPORTANCE This study revealed the microbial compositions in children with bacterial meningitis who were treated with antibiotics and made a comprehensive comparison between blood and CSF specimens for the risk and prognosis assessment. We found that microbiome signatures could distinguish patient subsets in the children and were correlated with the CRP level in blood and granulocyte percentage in CSF. The compositional changes in representative microbiota constituents could provide guidance for clinical monitoring and antibiotic intervention.

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          Most cited references65

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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            The Sequence Alignment/Map format and SAMtools

            Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: http://samtools.sourceforge.net Contact: rd@sanger.ac.uk
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              Fast and sensitive protein alignment using DIAMOND.

              The alignment of sequencing reads against a protein reference database is a major computational bottleneck in metagenomics and data-intensive evolutionary projects. Although recent tools offer improved performance over the gold standard BLASTX, they exhibit only a modest speedup or low sensitivity. We introduce DIAMOND, an open-source algorithm based on double indexing that is 20,000 times faster than BLASTX on short reads and has a similar degree of sensitivity.
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                Author and article information

                Contributors
                Role: Editor
                Role: ad hoc peer reviewer
                Journal
                mSystems
                mSystems
                msystems
                mSystems
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2379-5077
                8 June 2021
                May-Jun 2021
                8 June 2021
                : 6
                : 3
                : e00049-21
                Affiliations
                [a ]Key Laboratory of Molecular Genetics, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China
                [b ]Key Laboratory of Major Diseases in Children, Ministry of Education, Department of Infectious Diseases, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
                [c ]Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, Beijing, China
                University of California, San Francisco
                Javelin Biotech, Inc.
                Author notes

                Huiping Liao and Yuchao Zhang contributed equally to this work. The order of the authors was determined by the amount of work.

                Citation Liao H, Zhang Y, Guo W, Wang X, Wang H, Ye H, Wu K, Zhang Y-H, Guo L, Zhu Y, Guo Y, Hu L, Liu G, Kong X. 2021. Characterization of the blood and cerebrospinal fluid microbiome in children with bacterial meningitis and its potential correlation with inflammation. mSystems 6:e00049-21. https://doi.org/10.1128/mSystems.00049-21.

                Author information
                https://orcid.org/0000-0002-3688-8967
                https://orcid.org/0000-0001-6785-3719
                Article
                mSystems00049-21
                10.1128/mSystems.00049-21
                8269202
                34100633
                fcba4122-e994-48e2-843f-ba6cc581a57c
                Copyright © 2021 Liao et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 19 January 2021
                : 14 May 2021
                Page count
                supplementary-material: 2, Figures: 6, Tables: 2, Equations: 0, References: 66, Pages: 14, Words: 9180
                Funding
                Funded by: Beijing Hospital Authority, FundRef https://doi.org/10.13039/100016126;
                Award ID: The Special Fund of the Pediatric Medical Coordinated Development Center XTZD20180501
                Award Recipient :
                Funded by: Beijing Hospital Authority, FundRef https://doi.org/10.13039/100016126;
                Award ID: Dengfeng Talent Training Plan DFL 20181201
                Award Recipient :
                Funded by: Beijing Municipal Excellent Talents Foundation, FundRef https://doi.org/10.13039/100012491;
                Award ID: 2018000021469G274
                Award Recipient :
                Funded by: CAS | Chinese Academy of Sciences Key Project (CAS Key Project), FundRef https://doi.org/10.13039/501100005151;
                Award ID: QYZDJ-SSW-SM01
                Award Recipient :
                Funded by: MOST | National Key Research and Development Program of China (973 Program), FundRef https://doi.org/10.13039/501100012166;
                Award ID: 2017YFA0103501
                Award Recipient :
                Funded by: National Natural Science Foundation of China (NSFC), FundRef https://doi.org/10.13039/501100001809;
                Award ID: 81570827
                Award Recipient :
                Funded by: Chinese Academy of Sciences (CAS), FundRef https://doi.org/10.13039/501100002367;
                Award ID: Special Fund for Strategic Pilot Technology XDA12010204
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                May/June 2021

                bacterial meningitis,children,metagenomics,microbiome
                bacterial meningitis, children, metagenomics, microbiome

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