Metagenomic signatures of early life hospitalization and antibiotic treatment in the infant gut microbiota and resistome persist long after discharge

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Summary

Because hospitalized preterm infants are vulnerable to infection, they receive frequent and often prolonged exposures to antibiotics. It is not known if the short-term effects of antibiotics on the preterm infant gut microbiota and resistome persist after discharge from neonatal intensive care units. Here, we use complementary metagenomic, culture based, and machine learning techniques to interrogate the gut microbiota and resistome of antibiotic-exposed preterm infants, during and after hospitalization, and compare these readouts to antibiotic-naïve healthy infants sampled synchronously. We find a persistently enriched gastrointestinal antibiotic resistome, prolonged carriage of multidrug resistant Enterobacteriaceae, and distinct antibiotic-driven patterns of microbiota and resistome assembly in extremely preterm infants who received early life antibiotics. The collateral damage of early life antibiotic treatment and hospitalization in preterm infants is long-lasting. We urge development of strategies to reduce these consequences in highly vulnerable neonatal populations.

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Fast Identification and Removal of Sequence Contamination from Genomic and Metagenomic Datasets

Robert Schmieder, Robert Edwards (2011)

High-throughput sequencing technologies have strongly impacted microbiology, providing a rapid and cost-effective way of generating draft genomes and exploring microbial diversity. However, sequences obtained from impure nucleic acid preparations may contain DNA from sources other than the sample. Those sequence contaminations are a serious concern to the quality of the data used for downstream analysis, causing misassembly of sequence contigs and erroneous conclusions. Therefore, the removal of sequence contaminants is a necessary and required step for all sequencing projects. We developed DeconSeq, a robust framework for the rapid, automated identification and removal of sequence contamination in longer-read datasets ( 150 bp mean read length). DeconSeq is publicly available as standalone and web-based versions. The results can be exported for subsequent analysis, and the databases used for the web-based version are automatically updated on a regular basis. DeconSeq categorizes possible contamination sequences, eliminates redundant hits with higher similarity to non-contaminant genomes, and provides graphical visualizations of the alignment results and classifications. Using DeconSeq, we conducted an analysis of possible human DNA contamination in 202 previously published microbial and viral metagenomes and found possible contamination in 145 (72%) metagenomes with as high as 64% contaminating sequences. This new framework allows scientists to automatically detect and efficiently remove unwanted sequence contamination from their datasets while eliminating critical limitations of current methods. DeconSeq's web interface is simple and user-friendly. The standalone version allows offline analysis and integration into existing data processing pipelines. DeconSeq's results reveal whether the sequencing experiment has succeeded, whether the correct sample was sequenced, and whether the sample contains any sequence contamination from DNA preparation or host. In addition, the analysis of 202 metagenomes demonstrated significant contamination of the non-human associated metagenomes, suggesting that this method is appropriate for screening all metagenomes. DeconSeq is available at http://deconseq.sourceforge.net/.

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Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis.

Adnan T Bhutta, Mario A. Cleves, Patrick H Casey … (2002)

The cognitive and behavioral outcomes of school-aged children who were born preterm have been reported extensively. Many of these studies have methodological flaws that preclude an accurate estimate of the long-term outcomes of prematurity. To estimate the effect of preterm birth on cognition and behavior in school-aged children. MEDLINE search (1980 to November 2001) for English-language articles, supplemented by a manual search of personal files maintained by 2 of the authors. We included case-control studies reporting cognitive and/or behavioral data of children who were born preterm and who were evaluated after their fifth birthday if the attrition rate was less than 30%. From the 227 reviewed studies, cognitive data from 15 studies and behavioral data from 16 studies were selected. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were extracted from each study, entered in a customized database, and reviewed twice to minimize error. Differences between the mean cognitive scores of cases and controls were pooled. Homogeneity across studies was formally tested using a general variance-based method and graphically using Galbraith plots. Linear meta-analysis regression models were fitted to explore the impact of birth weight and gestational age on cognitive outcomes. Study-specific relative risks (RRs) were calculated for the incidence of attention-deficit/hyperactivity disorder (ADHD) and pooled. Quality assessment of the studies was performed based on a 10-point scale. Publication bias was examined using Begg modified funnel plots and formally tested using the Egger weighted-linear regression method. Among 1556 cases and 1720 controls, controls had significantly higher cognitive scores compared with children who were born preterm (weighted mean difference, 10.9; 95% confidence interval [CI], 9.2-12.5). The mean cognitive scores of preterm-born cases and term-born controls were directly proportional to their birth weight (R(2) = 0.51; P<.001) and gestational age (R(2) = 0.49; P<.001). Age at evaluation had no significant correlation with mean difference in cognitive scores (R(2) = 0.12; P =.20). Preterm-born children showed increases in externalizing and internalizing behaviors in 81% of studies and had more than twice the RR for developing ADHD (pooled RR, 2.64; 95% CI, 1.85-3.78). No differences were noted in cognition and behaviors based on the quality of the study. Children who were born preterm are at risk for reduced cognitive test scores and their immaturity at birth is directly proportional to the mean cognitive scores at school age. Preterm-born children also show an increased incidence of ADHD and other behaviors.

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Inexpensive Multiplexed Library Preparation for Megabase-Sized Genomes

Michael Baym, Sergey Kryazhimskiy, Tami Lieberman … (2015)

Whole-genome sequencing has become an indispensible tool of modern biology. However, the cost of sample preparation relative to the cost of sequencing remains high, especially for small genomes where the former is dominant. Here we present a protocol for rapid and inexpensive preparation of hundreds of multiplexed genomic libraries for Illumina sequencing. By carrying out the Nextera tagmentation reaction in small volumes, replacing costly reagents with cheaper equivalents, and omitting unnecessary steps, we achieve a cost of library preparation of $8 per sample, approximately 6 times cheaper than the standard Nextera XT protocol. Furthermore, our procedure takes less than 5 hours for 96 samples. Several hundred samples can then be pooled on the same HiSeq lane via custom barcodes. Our method will be useful for re-sequencing of microbial or viral genomes, including those from evolution experiments, genetic screens, and environmental samples, as well as for other sequencing applications including large amplicon, open chromosome, artificial chromosomes, and RNA sequencing.

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Author and article information

Journal

Journal ID (nlm-journal-id): 101674869

Journal ID (pubmed-jr-id): 44774

Journal ID (nlm-ta): Nat Microbiol

Journal ID (iso-abbrev): Nat Microbiol

Title: Nature microbiology

ISSN (Electronic): 2058-5276

Publication date Nihms-submitted: 27 July 2019

Publication date (Electronic): 09 September 2019

Publication date (Print): December 2019

Publication date PMC-release: 09 March 2020

Volume: 4

Issue: 12

Pages: 2285-2297

Affiliations

[1 ]The Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA

[2 ]Department of Pathology and Immunology, Washington University in St, Louis School of Medicine, St. Louis, MO, USA

[3 ]Department of Pediatrics, Washington University in St Louis School of Medicine, St. Louis, MO, USA

[4 ]Department of Molecular Microbiology, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA

[5 ]Department of Biomedical Engineering, Washington University in St Louis, Saint Louis, MO, USA

Author notes

Author Contributions

A.J.G and G.D. conceived and designed the study. P.I.T, B.B.W, and I.M.N. assembled the cohorts, collected the biologics and maintained the database, oversaw transfer of biologics and clinical metadata, provided clinical insight. A.J.G. and B.W. extracted metagenomic DNA from stools and prepared shotgun metagenomic sequencing libraries. A.J.G., B.W., and A.H-L. performed stool culturing experiments and isolate genomic DNA extraction. A.J.G. and B.W. prepared isolate genome sequencing libraries. E.A.K. performed Enterococcus phenotyping experiments. X.S. created functional metagenomic libraries, performed functional selections, and prepared functional metagenomic sequencing libraries. A.J.G. analyzed clinical metadata, shotgun metagenomic sequencing data, isolate genome sequencing data, and functional metagenomic data. A.J.G. wrote the manuscript with input from G.D., B.B.W., and P.I.T.

[* ] Correspondence and requests for materials should be addressed to G.D. dantas@ 123456wustl.edu

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Manuscript ID: NIHMS1535894

DOI: 10.1038/s41564-019-0550-2

PMC ID: 6879825

PubMed ID: 31501537

SO-VID: eaaea918-0cd6-4c2d-8f9f-12ebdb28e6a2

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Metagenomic signatures of early life hospitalization and antibiotic treatment in the infant gut microbiota and resistome persist long after discharge

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Role of Microbes in Soil Fertility and Human Health

Most cited references 50

Fast Identification and Removal of Sequence Contamination from Genomic and Metagenomic Datasets

Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis.

Inexpensive Multiplexed Library Preparation for Megabase-Sized Genomes

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