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      Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants

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          Abstract

          Antibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the routine early antibiotic use in symptomatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 h after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered between Veillonella and the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.

          Trial Registration This project is registered at clinicaltrials.gov under the name “Antibiotic ‘Dysbiosis’ in Preterm Infants” with trial number NCT02784821.

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            DADA2: High resolution sample inference from Illumina amplicon data

            We present DADA2, a software package that models and corrects Illumina-sequenced amplicon errors. DADA2 infers sample sequences exactly, without coarse-graining into OTUs, and resolves differences of as little as one nucleotide. In several mock communities DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.
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              The SILVA ribosomal RNA gene database project: improved data processing and web-based tools

              SILVA (from Latin silva, forest, http://www.arb-silva.de) is a comprehensive web resource for up to date, quality-controlled databases of aligned ribosomal RNA (rRNA) gene sequences from the Bacteria, Archaea and Eukaryota domains and supplementary online services. The referred database release 111 (July 2012) contains 3 194 778 small subunit and 288 717 large subunit rRNA gene sequences. Since the initial description of the project, substantial new features have been introduced, including advanced quality control procedures, an improved rRNA gene aligner, online tools for probe and primer evaluation and optimized browsing, searching and downloading on the website. Furthermore, the extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches.
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                Author and article information

                Contributors
                ewt@ufl.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                21 January 2021
                21 January 2021
                2021
                : 11
                : 1943
                Affiliations
                [1 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, , University of Florida, ; Gainesville, FL USA
                [2 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, Division of Neonatology, Department of Pediatrics, , University of Florida, ; Gainesville, FL USA
                [3 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, , University of Florida, ; Gainesville, FL USA
                [4 ]GRID grid.21729.3f, ISNI 0000000419368729, Department of Pediatrics, College of Physicians and Surgeons, , Columbia University, ; New York, NY USA
                Article
                80982
                10.1038/s41598-021-80982-6
                7820285
                33479274
                4b645270-c5e6-4560-b43f-f13226cd147b
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 September 2020
                : 1 January 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R21HD088005
                Award ID: R21HD088005
                Award ID: R21HD088005
                Award Recipient :
                Categories
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                © The Author(s) 2021

                Uncategorized
                microbiology,medical research
                Uncategorized
                microbiology, medical research

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